40 results on '"Wolfgang Kothny"'
Search Results
2. Effects of Vildagliptin on Ventricular Function in Patients With Type 2 Diabetes Mellitus and Heart Failure
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Wolfgang Kothny, Henry Krum, James Lewsey, Geremia B. Bolli, Plamen Kozlovski, Valentina Lukashevich, John J.V. McMurray, and Piotr Ponikowski
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medicine.medical_specialty ,Ejection fraction ,business.industry ,Placebo-controlled study ,Type 2 Diabetes Mellitus ,Type 2 diabetes ,030204 cardiovascular system & hematology ,medicine.disease ,Placebo ,03 medical and health sciences ,0302 clinical medicine ,Heart failure ,Internal medicine ,Diabetes mellitus ,medicine ,Cardiology ,Vildagliptin ,030212 general & internal medicine ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
Objectives This study sought to examine the safety of the dipeptidyl peptidase-4 inhibitor, vildagliptin, in patients with heart failure and reduced ejection fraction. Background Many patients with type 2 diabetes mellitus have heart failure and it is important to know about the safety of new treatments for diabetes in these individuals. Methods Patients 18 to 85 years of age with type 2 diabetes and heart failure (New York Heart Association functional class I to III and left ventricular ejection fraction [LVEF] Results A total of 254 patients were randomly assigned to vildagliptin (n = 128) or placebo (n = 126). Baseline LVEF was 30.6 ± 6.8% in the vildagliptin group and 29.6 ± 7.7% in the placebo group. The adjusted mean change in LVEF was 4.95 ± 1.25% in vildagliptin treated patients and 4.33 ± 1.23% in placebo treated patients, a difference of 0.62 (95% confidence interval [CI]: −2.21 to 3.44; p = 0.667). This difference met the predefined noninferiority margin of −3.5%. Left ventricular end-diastolic and end-systolic volumes increased more in the vildagliptin group by 17.1 ml (95% CI: 4.6 to 29.5 ml; p = 0.007) and 9.4 ml (95% CI: −0.49 to 19.4 ml; p = 0.062), respectively. Decrease in hemoglobin A1c from baseline to 16 weeks, the main secondary endpoint, was greater in the vildagliptin group: −0.62% (95% CI: −0.93 to −0.30%; p Conclusions Compared with placebo, vildagliptin had no major effect on LVEF but did lead to an increase in left ventricular volumes, the cause and clinical significance of which is unknown. More evidence is needed regarding the safety of dipeptidyl peptidase-4 inhibitors in patients with heart failure and left ventricular systolic dysfunction. (Effect of Vildagliptin on Left Ventricular Function in Patients With Type 2 Diabetes and Congestive Heart Failure; NCT00894868)
- Published
- 2018
3. Effect of race and ethnicity on vildagliptin efficacy: A pooled analysis of phase II and III studies
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Päivi M. Paldánius, Valentina Lukashevich, Wolfgang Kothny, Plamen Kozlovski, Viswanathan Mohan, Masato Odawara, and Marília I.H. Fonseca
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Blood Glucose ,Male ,Pyrrolidines ,Endocrinology, Diabetes and Metabolism ,Ethnic group ,Adamantane ,030204 cardiovascular system & hematology ,0302 clinical medicine ,Endocrinology ,Japan ,Ethnicity ,Insulin ,Vildagliptin ,race ,Randomized Controlled Trials as Topic ,Incidence (epidemiology) ,DPP‐4 inhibitor ,Middle Aged ,Metformin ,Treatment Outcome ,Female ,Original Article ,medicine.drug ,Adult ,China ,medicine.medical_specialty ,Asia ,India ,030209 endocrinology & metabolism ,Caucasian ,Placebo ,White People ,03 medical and health sciences ,Clinical Trials, Phase II as Topic ,Asian People ,Internal medicine ,Diabetes mellitus ,Nitriles ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Aged ,Glycated Hemoglobin ,Dipeptidyl-Peptidase IV Inhibitors ,business.industry ,Racial Groups ,Type 2 Diabetes Mellitus ,Repeated measures design ,Original Articles ,medicine.disease ,Clinical trial ,Sulfonylurea Compounds ,Clinical Trials, Phase III as Topic ,Diabetes Mellitus, Type 2 ,business - Abstract
Aims To determine the impact of race and ethnicity on the efficacy, body weight and hypoglycaemia incidence with vildagliptin treatment in patients with type 2 diabetes mellitus using patient-level data from the vildagliptin clinical trial programme. Methods Data from 22 randomized, placebo-controlled global and local (Japan, China) registration studies of vildagliptin (50 mg once-daily or twice-daily) of ≥12-week duration were analysed by race (Caucasian [n = 2764] and Asian [n = 2232]) and by ethnicity (Japanese, Chinese, and Indian). The placebo-subtracted differences in the change in glycated haemoglobin (HbA1c) and body weight from baseline to week 12 or week 24 were evaluated by race or ethnicity using repeated measure analysis of unstructured covariance. Hypoglycaemia incidences were summarized using descriptive statistics. Results The HbA1c reduction from baseline with vildagliptin was similar across the racial/ethnic subgroups (−0.83% ± 0.02% to −1.01% ± 0.05%). Placebo-corrected HbA1c reduction was similar between Caucasian (−0.68% ± 0.03%) and Asian (−0.80% ± 0.03%) patients ( P value for interaction = .56); analysis by race and ethnicity showed better efficacy ( P < .02) in Japanese patients. Japanese patients were drug-naive and treated with a single oral anti-diabetes drug only; they showed no response to placebo. Weight neutrality of vildagliptin was demonstrated in all groups (0.47 ± 0.11 kg to −0.29 ± 0.08 kg). Hypoglycaemic events (≥1) were infrequent in all ethnic subgroups. Conclusions The glycaemic efficacy of vildagliptin was similar in Caucasian and Asian patients. The slightly better efficacy observed in Japanese patients was driven by the absence of placebo effect and might be explained by their earlier stage of diabetes compared to other subgroups.
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- 2017
4. Review for 'Efficacy and safety of gemigliptin as add‐on therapy to insulin with or without metformin in patients with type 2 diabetes mellitus (ZEUS II study)'
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Wolfgang Kothny
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medicine.medical_specialty ,business.industry ,Insulin ,medicine.medical_treatment ,Type 2 Diabetes Mellitus ,Zeus (malware) ,Gemigliptin ,Metformin ,Add on therapy ,Internal medicine ,medicine ,In patient ,business ,medicine.drug - Published
- 2019
5. Vildagliptin as add-on therapy to insulin improves glycemic control without increasing risk of hypoglycemia in Asian, predominantly Chinese, patients with type 2 diabetes mellitus
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Xiaofeng Lv, Jianhua Ma, Guang Ning, Wei Wang, Ling Li, Wolfgang Kothny, Ming Yang, Valentina Lukashevich, Weiqing Wang, and Michael Woloschak
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medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,Insulin ,medicine.medical_treatment ,Type 2 Diabetes Mellitus ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,Hypoglycemia ,medicine.disease ,Gastroenterology ,Add on therapy ,03 medical and health sciences ,Increasing risk ,0302 clinical medicine ,Endocrinology ,Internal medicine ,Diabetes mellitus ,medicine ,Vildagliptin ,business ,Glycemic ,medicine.drug - Abstract
Background The aim of the present study was to investigate the efficacy and safety of vildagliptin added onto insulin with or without metformin in an Asian, predominantly Chinese, population with type 2 diabetes mellitus (T2DM). Methods In this 24-week, multicenter, double-blind, placebo-controlled trial, patients with T2DM inadequately controlled (HbA1c 7.5%–11.0%) on stable therapy with long-acting, intermediate-acting, or premixed insulin, with or without concomitant metformin, were randomized to receive vildagliptin 50 mg b.i.d. or placebo. Results Of 293 patients randomized, 146 received vildagliptin and 147 received placebo treatment. At baseline, the overall mean age of patients was 58.1 years, mean T2DM duration was 11.3 years, and mean HbA1c was 8.7%. The adjusted mean (±SE) change in HbA1c at Week 24 in the vildagliptin and placebo groups was −1.08 ± 0.12% and −0.38 ± 0.12%, respectively (between-treatment difference −0.70 ± 0.16%; P
- Published
- 2016
6. Exploring Hepatic Safety of the Dipeptidyl Peptidase-4 (DPP-4) Inhibitor Vildagliptin in a Real-World Setting
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Päivi M. Paldánius, Wolfgang Kothny, Rachael Williams, Carmen Serban, and Raymond G. Schlienger
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medicine.medical_specialty ,Safety studies ,business.industry ,Endocrinology, Diabetes and Metabolism ,Confidence interval ,law.invention ,Clinical trial ,Randomized controlled trial ,law ,Internal medicine ,Internal Medicine ,Medicine ,Vildagliptin ,Medical prescription ,business ,Dipeptidyl peptidase-4 ,medicine.drug ,Cohort study - Abstract
Since the introduction of DPP-4 inhibitors, vildagliptin has accumulated extensive efficacy/effectiveness and safety data from various meta-analyses of clinical trials, large randomized controlled trials, non-interventional studies, and post-authorization safety studies. In this non-interventional post-authorization study, we explored if vildagliptin is associated with an increased risk of hepatic events vs. other non-insulin antidiabetic drugs (NIADs) in a real-world setting. A cohort study was performed in adult T2DM patients with a vildagliptin or NIAD prescription between January 20and June 2014 with data from five European electronic healthcare databases from the UK (CPRD), Germany and France (IMS), Denmark (OPED) and Sweden (National Registers). Patients with cancer, HIV/AIDS or insulin prior to the index date (date of first vildagliptin or NIAD prescription in the study period) were excluded. Age- and sex-adjusted incidence rate ratios (aIRRs) were estimated in current vildagliptin vs. current other NIAD users using negative binomial regression. We included 738,054 patients, of which 20,973 received vildagliptin (mean follow-up 1.4 years, 28,330 cumulative vildagliptin patient-years). The database-specific aIRR estimates for serious hepatic events were not suggestive of an increased risk with vildagliptin (range of individual aIRR: 0.29-0.55), with two data sources having an upper limit of the 95% confidence interval (CI) 3-times upper limit of normal (ULN) together with bilirubin >2-times ULN (only assessed in CPRD) was 0.72 (95% CI: 0.42-1.25). In this real-world setting there was no evidence of an increased risk of hepatic toxicity with vildagliptin exposure compared to other NIADs across five European databases. Disclosure R. Williams: Employee; Self; Clinical Practice Research Datalink, London, UK. W. Kothny: Employee; Self; Novartis AG. Stock/Shareholder; Self; Novartis AG. C. Serban: Employee; Self; Novartis AG. Stock/Shareholder; Self; Novartis AG. P.M. Paldánius: Employee; Self; Novartis AG. Stock/Shareholder; Self; Novartis AG. R. Schlienger: Employee; Self; Novartis AG. Stock/Shareholder; Self; Novartis AG.
- Published
- 2018
7. Cardiovascular and heart failure safety profile of vildagliptin: a meta-analysis of 17 000 patients
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S. Del Prato, Anja Schweizer, Wolfgang Kothny, Marc Evans, Michael Stumvoll, Valentina Lukashevich, Q. Shao, and G. McInnes
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Male ,medicine.medical_specialty ,Pyrrolidines ,Endocrinology, Diabetes and Metabolism ,Adamantane ,Dipeptidyl peptidase-4 inhibitor ,Antidiabetic drug ,Endocrinology ,Internal medicine ,Nitriles ,Internal Medicine ,medicine ,Clinical endpoint ,Humans ,Hypoglycemic Agents ,Vildagliptin ,Myocardial infarction ,Aged ,Randomized Controlled Trials as Topic ,Retrospective Studies ,Aged, 80 and over ,Glycated Hemoglobin ,Heart Failure ,Dipeptidyl-Peptidase IV Inhibitors ,business.industry ,Middle Aged ,Cardiovascular disease ,Meta-analysis ,medicine.disease ,Confidence interval ,Surgery ,Diabetes and Metabolism ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,Relative risk ,Cardiology ,Female ,business ,Body mass index ,Mace ,medicine.drug - Abstract
Aims To report the cardiovascular (CV) safety profile and heart failure (HF) risk of vildagliptin from a large pool of studies, including trials in high-risk patients with type 2 diabetes mellitus (T2DM), such as those with congestive HF and/or moderate/severe renal impairment. Methods We conducted a retrospective meta-analysis of prospectively adjudicated CV events. Patient-level data were pooled from 40 double-blind, randomized controlled phase III and IV vildagliptin studies. The primary endpoint was occurrence of major adverse CV events (MACEs; myocardial infarction, stroke and CV death). Assessments of the individual MACE components and HF events (requiring hospitalization or new onset) were secondary endpoints. The risk ratio (RR) of vildagliptin (50 mg once- and twice-daily combined) versus comparators (placebo and all non-vildagliptin treatments) was calculated using the Mantel–Haenszel (M–H) method. Results Of the 17 446 patients, 9599 received vildagliptin (9251.4 subject-years of exposure) and 7847 received comparators (7317.0 subject-years of exposure). The mean age of the patients was 57 years, body mass index 30.5 kg/m2 (nearly 50% obese), glycated haemoglobin concentration 8.1% and T2DM duration 5.5 years. A MACE occurred in 83 (0.86%) vildagliptin-treated patients and 85 (1.20%) comparator-treated patients, with an M-H RR of 0.82 [95% confidence interval (CI) 0.61–1.11]. Similar RRs were observed for the individual events. Confirmed HF events were reported in 41 (0.43%) vildagliptin-treated patients and 32 (0.45%) comparator-treated patients, with an M–H RR 1.08 (95% CI 0.68–1.70). Conclusions This large meta-analysis indicates that vildagliptin is not associated with an increased risk of adjudicated MACEs relative to comparators. Moreover, this analysis did not find a significant increased risk of HF in vildagliptin-treated patients.
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- 2015
8. Comparison of vildagliptin and sitagliptin in patients with type 2 diabetes and severe renal impairment: a randomised clinical trial
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Wolfgang Kothny, Valentina Lukashevich, James E. Foley, Anja Schweizer, and Marc Rendell
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Blood Glucose ,Male ,medicine.medical_specialty ,Pyrrolidines ,Endocrinology, Diabetes and Metabolism ,Adamantane ,Type 2 diabetes ,Pharmacology ,Article ,Sitagliptin Phosphate ,law.invention ,Double-Blind Method ,Randomized controlled trial ,law ,Diabetes mellitus ,Internal medicine ,Nitriles ,Internal Medicine ,medicine ,Sitagliptin ,Humans ,Hypoglycemic Agents ,In patient ,Vildagliptin ,Renal impairment ,Aged ,Glycated Hemoglobin ,business.industry ,Middle Aged ,medicine.disease ,United States ,Clinical trial ,Diabetes Mellitus, Type 2 ,Female ,Kidney Diseases ,business ,Brazil ,medicine.drug - Abstract
Aims/hypothesis There are limited data comparing dipeptidyl peptidase-4 (DPP-4) inhibitors directly. We compared the safety and efficacy of vildagliptin and sitagliptin in patients with type 2 diabetes and severe renal impairment (RI). Methods This study was a parallel-arm, randomised, multicentre, double-blind, 24 week study conducted in 87 centres across Brazil and the USA. Patients with type 2 diabetes, either drug naive or treated with any glucose-lowering agents, who had inadequate glycaemic control (HbA1c 6.5–10.0% [48–86 mmol/mol]) and an estimated GFR
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- 2015
9. Efficacy and Safety of a Single-Pill Combination of Vildagliptin and Metformin in Japanese Patients with Type 2 Diabetes Mellitus: A Randomized, Double-Blind, Placebo-Controlled Trial
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Masato Odawara, Wolfgang Kothny, Valentina Lukashevich, Mika Yoshiki, Misako Sano, and Izumi Hamada
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medicine.medical_specialty ,animal structures ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Placebo-controlled study ,Dipeptidyl peptidase-4 inhibitor ,Pharmacology ,Double blind ,Diabetes mellitus ,Internal medicine ,Type 2 diabetes mellitus ,Internal Medicine ,medicine ,Vildagliptin ,Original Research ,Single pill combination ,business.industry ,Single-pill combination ,fungi ,digestive, oral, and skin physiology ,nutritional and metabolic diseases ,Type 2 Diabetes Mellitus ,medicine.disease ,Metformin ,business ,medicine.drug - Abstract
Introduction The use of dipeptidyl peptidase-4 inhibitors in combination with metformin is increasing in Japanese patients with type 2 diabetes mellitus (T2DM), but no single-pill combination (SPC) is currently available in Japan. The objective of this study was to assess the efficacy and safety of vildagliptin/metformin SPC in Japanese patients with T2DM inadequately controlled with vildagliptin monotherapy. Methods This was a 14-week, randomized, double-blind, parallel-group, placebo-controlled trial. 171 patients with T2DM inadequately controlled [HbA1c (glycosylated hemoglobin) 7.0–10.0%] with vildagliptin 50 mg twice daily (bid) were randomized (2:1) to receive either a vildagliptin/metformin SPC (n = 115) or matching vildagliptin/placebo SPC (n = 56). Results Baseline demographics and background characteristics were generally comparable between the treatment groups. The change in HbA1c [mean ± standard error (SE)] was −0.8 ± 0.1% in the vildagliptin/metformin SPC (baseline HbA1c, 7.9 ± 0.1%) group and 0.1 ± 0.1% in the vildagliptin/placebo SPC (baseline HbA1c, 8.0 ± 0.1%) group, with a between-treatment difference of −1.0 ± 0.1% (P
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- 2015
10. Cardiovascular safety of vildagliptin in patients with type 2 diabetes: A European multi-database, non-interventional post-authorization safety study
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Changan Chu, Wolfgang Kothny, Frank de Vries, Sandra Lopez-Leon, Raymond G. Schlienger, Carmen Serban, Rachael Williams, Farmacologie en Toxicologie, MUMC+: DA KFT Medische Staf (9), and RS: CAPHRI - R5 - Optimising Patient Care
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Adult ,Male ,Acute coronary syndrome ,Pyrrolidines ,Databases, Factual ,Diabetic Cardiomyopathies ,Endocrinology, Diabetes and Metabolism ,Adamantane ,030209 endocrinology & metabolism ,Type 2 diabetes ,030204 cardiovascular system & hematology ,computer.software_genre ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,cardiovascular disease ,Nitriles ,Internal Medicine ,medicine ,Humans ,DPP-4 inhibitor ,Vildagliptin ,Myocardial infarction ,Stroke ,Aged ,Retrospective Studies ,Database ,business.industry ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Cardiotoxicity ,Confidence interval ,Europe ,Diabetes Mellitus, Type 2 ,vildagliptin ,Female ,observational study ,type 2 diabetes ,business ,computer ,Cohort study ,medicine.drug - Abstract
The aim of this non-interventional, multi-database, analytical cohort study was to assess the cardiovascular (CV) safety of vildagliptin vs other non-insulin antidiabetic drugs (NIADs) using real-world data from 5 European electronic healthcare databases. Patients with type 2 diabetes aged >= 18 years on NIAD treatment were enrolled. Adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the outcomes of interest (myocardial infarction [MI], acute coronary syndrome [ACS], stroke, congestive heart failure [CHF], individually and as a composite) were estimated using negative binomial regression. Approximately 2.8% of the enrolled patients (n = 738 054) used vildagliptin at any time during the study, with an average followup time of 1.4 years, resulting in a cumulative current vildagliptin exposure of 28 330 person-years. The adjusted IRRs (vildagliptin [+other NIADs] vs other NIADs) were in the range of 0.61 to 0.97 (MI), 0.55 to 1.60 (ACS), 0.02 to 0.77 (stroke), 0.49 to 1.03 (CHF), and 0.22 to 1.02 (composite CV outcomes). The IRRs and their 95% CIs were close to 1, demonstrating no increased risk of adverse CV events, including the risk of CHF, with vildagliptin vs other NIADs in real-world conditions.
- Published
- 2017
11. Estimands: A More Strategic Approach to Study Design and Analysis
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Wolfgang Kothny and Mouna Akacha
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Pharmacology ,Models, Statistical ,Computer science ,Management science ,Harmonization ,01 natural sciences ,law.invention ,Clinical trial ,010104 statistics & probability ,03 medical and health sciences ,0302 clinical medicine ,Strategic approach ,law ,Research Design ,Data Interpretation, Statistical ,CLARITY ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,0101 mathematics ,Randomized Controlled Trials as Topic - Abstract
Do we always precisely define the treatment effects that our clinical trial will estimate? Our tenet is that this is not always done, or is done inadequately. This lack of clarity can result in a misalignment among trial objectives, trial design, and statistical methods. We will discuss these challenges and present an improved framework using estimands that is proposed in a draft International Council for Harmonization (ICH) E9 addendum.
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- 2017
12. Effects of Vildagliptin on Ventricular Function in Patients With Type 2 Diabetes Mellitus and Heart Failure: A Randomized Placebo-Controlled Trial
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John J V, McMurray, Piotr, Ponikowski, Geremia B, Bolli, Valentina, Lukashevich, Plamen, Kozlovski, Wolfgang, Kothny, James D, Lewsey, and Henry, Krum
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Adult ,Aged, 80 and over ,Heart Failure ,Male ,Vildagliptin ,Adolescent ,Dose-Response Relationship, Drug ,Systole ,Heart Ventricles ,Stroke Volume ,Middle Aged ,Ventricular Function, Left ,Young Adult ,Diabetes Mellitus, Type 2 ,Double-Blind Method ,Echocardiography ,Humans ,Hypoglycemic Agents ,Female ,Prospective Studies ,Aged ,Follow-Up Studies - Abstract
This study sought to examine the safety of the dipeptidyl peptidase-4 inhibitor, vildagliptin, in patients with heart failure and reduced ejection fraction.Many patients with type 2 diabetes mellitus have heart failure and it is important to know about the safety of new treatments for diabetes in these individuals.Patients 18 to 85 years of age with type 2 diabetes and heart failure (New York Heart Association functional class I to III and left ventricular ejection fraction [LVEF] 0.40) were randomized to 52 weeks treatment with vildagliptin 50 mg twice daily (50 mg once daily if treated with a sulfonylurea) or matching placebo. The primary endpoint was between-treatment change from baseline in echocardiographic LVEF using a noninferiority margin of -3.5%.A total of 254 patients were randomly assigned to vildagliptin (n = 128) or placebo (n = 126). Baseline LVEF was 30.6 ± 6.8% in the vildagliptin group and 29.6 ± 7.7% in the placebo group. The adjusted mean change in LVEF was 4.95 ± 1.25% in vildagliptin treated patients and 4.33 ± 1.23% in placebo treated patients, a difference of 0.62 (95% confidence interval [CI]: -2.21 to 3.44; p = 0.667). This difference met the predefined noninferiority margin of -3.5%. Left ventricular end-diastolic and end-systolic volumes increased more in the vildagliptin group by 17.1 ml (95% CI: 4.6 to 29.5 ml; p = 0.007) and 9.4 ml (95% CI: -0.49 to 19.4 ml; p = 0.062), respectively. Decrease in hemoglobin ACompared with placebo, vildagliptin had no major effect on LVEF but did lead to an increase in left ventricular volumes, the cause and clinical significance of which is unknown. More evidence is needed regarding the safety of dipeptidyl peptidase-4 inhibitors in patients with heart failure and left ventricular systolic dysfunction. (Effect of Vildagliptin on Left Ventricular Function in Patients With Type 2 Diabetes and Congestive Heart Failure; NCT00894868).
- Published
- 2017
13. Vildagliptin added to sulfonylurea improves glycemic control without hypoglycemia and weight gain in Chinese patients with type 2 diabetes mellitus 中国2型糖尿病患者使用磺脲类药物联合维格列汀可改善血糖控制且无低血糖及体重增加
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Yiming Li, Guoyue Yuan, Feifei Sun, Xiaofeng Lv, Plamen Kozlovski, Wolfgang Kothny, Wei Wang, Valentina Lukashevich, Xiaoping Xing, Jianhua Ma, Wenying Yang, and Michael Woloschak
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medicine.medical_specialty ,medicine.drug_class ,business.industry ,Endocrinology, Diabetes and Metabolism ,nutritional and metabolic diseases ,Type 2 Diabetes Mellitus ,Hypoglycemia ,medicine.disease ,Placebo ,Sulfonylurea ,Gastroenterology ,Glimepiride ,Endocrinology ,Diabetes mellitus ,Internal medicine ,medicine ,Vildagliptin ,medicine.symptom ,business ,Weight gain ,medicine.drug - Abstract
Objective The aim of the present study was to assess the efficacy and safety of vildagliptin as add-on to sulfonylurea therapy in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on sulfonylurea monotherapy. Methods The 24-week randomized double-blind placebo-controlled study compared vildagliptin 50 mg, q.d., with placebo as add-on to glimepiride in T2DM patients who were inadequately controlled (HbA1c 7.5%–11.0% [58–97 mmol/mol]) on a stable dose of sulfonylurea for ≥12 weeks before study entry. Results In all, 279 patients were randomized to receive either vildagliptin (n = 143) or placebo (n = 136). At baseline, overall mean age was 58.5 years, body weight 68.1 kg, duration of diabetes 6.9 years and daily glimepiride dose 3.3 mg. After 24 weeks, the adjusted mean change (AMΔ) in HbA1c was −0.7% (−8 mmol/mol; baseline 8.6%, 70 mmol/mol) in the vildagliptin group and −0.2% (−2 mmol/mol; baseline 8.7%, 72 mmol/mol) in the placebo group, with a treatment difference of −0.5% (−5 mmol/mol; P
- Published
- 2014
14. Pancreatic safety of vildagliptin in patients with type 2 diabetes mellitus: A European, noninterventional, postauthorization safety study
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Wolfgang Kothny, Rachael Williams, Sandra Lopez-Leon, Raymond G. Schlienger, and Carmen Serban
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medicine.medical_specialty ,type 2 diabetes mellitus ,business.industry ,Endocrinology, Diabetes and Metabolism ,pancreatic cancer ,Confounding ,pancreatitis ,Original Articles ,Type 2 diabetes ,medicine.disease ,Confidence interval ,vildagliptin ,Internal medicine ,Pancreatic cancer ,medicine ,Pancreatitis ,Acute pancreatitis ,Original Article ,Vildagliptin ,dipeptidyl peptidase‐4 inhibitors ,business ,medicine.drug ,Cohort study - Abstract
This cohort study assessed the pancreatic safety of vildagliptin versus other noninsulin antidiabetic drugs (NIADs) based on data from five European electronic health care databases. Patients with type 2 diabetes aged ≥18 years on NIAD treatment were enrolled. Adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated separately for acute pancreatitis and pancreatic cancer for vildagliptin (± other NIADs) compared with other NIADs using negative binomial regression. Approximately 2.8% of the enrolled patients (n = 738 054) used vildagliptin during the study, with an average follow‐up time of 1.4 years. For acute pancreatitis, adjusted IRRs ranged between 0.89 andt 2.58 with all corresponding 95% CIs crossing 1. For pancreatic cancer adjusted IRRs ranged from 0.56 to 3.64, with the lower limit of 95% CIs >1 in some analyses. Post hoc sensitivity analyses taking latency time into account markedly lowered the risk estimates with corresponding 95% CIs crossing 1. Overall, the results do not suggest an increased pancreatitis risk with vildagliptin, while the observation for pancreatic cancer have to be interpreted carefully as this study was not designed to assess pancreatic cancer and rather be explained by certain underlying limitations including latency ‐time, chance findings and/or bias and confounding.
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- 2019
15. Effectiveness and tolerability of second-line therapy with vildagliptin vs. other oral agents in type 2 diabetes: A real-life worldwide observational study (EDGE)
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Wolfgang Kothny, Emmanouil Pagkalos, R Göke, Nicolaas C. Schaper, J J de Castro, Helmut Brath, E Márquez Rodriguez, Ignacio Conget, Chantal Mathieu, P. M. Nilsson, S K Wangnoo, A Penfornis, Giovanni Bader, Anthony H. Barnett, MUMC+: MA Endocrinologie (9), Interne Geneeskunde, and RS: CARIM School for Cardiovascular Diseases
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Male ,medicine.medical_specialty ,Pyrrolidines ,METFORMIN ,Administration, Oral ,Adamantane ,Type 2 diabetes ,Medicine, General & Internal ,Pharmacotherapy ,Endocrinology ,General & Internal Medicine ,Internal medicine ,Nitriles ,medicine ,Humans ,Hypoglycemic Agents ,Vildagliptin ,Pharmacology & Pharmacy ,Prospective Studies ,COMBINATION ,Prospective cohort study ,Glycated Hemoglobin ,COMPLICATIONS ,Science & Technology ,BLOOD-GLUCOSE CONTROL ,business.industry ,ADVERSE DRUG-REACTIONS ,General Medicine ,Odds ratio ,Middle Aged ,EFFICACY ,medicine.disease ,Hypoglycemia ,Surgery ,PROPENSITY SCORE ,Regimen ,Tolerability ,Diabetes Mellitus, Type 2 ,SAFETY ,Cohort ,PIOGLITAZONE ,Drug Therapy, Combination ,Female ,business ,Life Sciences & Biomedicine ,CLINICAL-TRIALS ,medicine.drug - Abstract
Aim Real-life studies are needed to confirm the clinical relevance of findings from randomised controlled trials (RCTs). This study aimed to assess the effectiveness and tolerability of vildagliptin add-on vs. other oral antihyperglycaemic drugs (OADs) added to OAD monotherapy in a real-life setting, and to explore the advantages and limitations of large-scale ‘pragmatic’ trials. Methods EDGE was a prospective, 1-year, worldwide, real-life observational study in which 2957 physicians reported on the effects of second-line OADs in 45,868 patients with T2DM not reaching glycaemic targets with monotherapy. Physicians could add any OAD, and patients entered either vildagliptin or (pooled) comparator cohort. The primary effectiveness and tolerability end-point (PEP) evaluated proportions of patients decreasing HbA1c > 0.3%, without hypoglycaemia, weight gain, peripheral oedema or gastrointestinal side effects. The most clinically relevant secondary end-point (SEP 3) was attainment of end-point HbA1c
- Published
- 2013
16. Individualised treatment targets for elderly patients with type 2 diabetes using vildagliptin add-on or lone therapy (INTERVAL): a 24 week, randomised, double-blind, placebo-controlled study
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Päivi M. Paldánius, Marie-Jose Hoellinger, W. David Strain, Wolfgang Kothny, and Valentina Lukashevich
- Subjects
Male ,medicine.medical_specialty ,Pyrrolidines ,Population ,Placebo-controlled study ,Adamantane ,Type 2 diabetes ,Placebo ,law.invention ,Double-Blind Method ,Randomized controlled trial ,law ,Internal medicine ,Nitriles ,medicine ,Humans ,Hypoglycemic Agents ,media_common.cataloged_instance ,Vildagliptin ,Precision Medicine ,European union ,education ,Aged ,media_common ,Aged, 80 and over ,Glycated Hemoglobin ,education.field_of_study ,business.industry ,General Medicine ,medicine.disease ,Hypoglycemia ,Metformin ,Surgery ,Sulfonylurea Compounds ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,Tolerability ,Feasibility Studies ,Drug Therapy, Combination ,Female ,business ,medicine.drug - Abstract
Guidelines suggest setting individualised targets for glycaemic control in elderly patients with type 2 diabetes, despite no evidence. We aimed to assess the feasibility of setting and achieving individualised targets over 24 weeks along with conventional HbA1c reduction using vildagliptin versus placebo.In this multinational, double-blind, 24 week study, we enrolled drug-naive or inadequately controlled (glycosylated haemoglobin A1c [HbA1c] ≥7·0% to ≤10·0%) patients with type 2 diabetes aged 70 years or older from 45 outpatient centres in Europe. Investigators set individualised treatment targets on the basis of age, baseline HbA1c, comorbidities, and frailty status before a validated automated system randomly assigned patients (1:1) to vildagliptin (50 mg once or twice daily as per label) or placebo. Coprimary efficacy endpoints were proportion of patients reaching their investigator-defined HbA1c target and HbA1c reduction from baseline to study end. The study is registered with ClinicalTrials.gov, number NCT01257451, and European Union Drug Regulating Authorities Clinical Trials database, number 2010-022658-18.Between Dec 22, 2010, and March 14, 2012, we randomly assigned 139 patients each to the vildagliptin and placebo groups. 37 (27%) of 137 patients in the placebo group achieved their individualised targets by education and interactions with the study team alone and 72 (52·6%) of 137 patients achieved their target in the vildagliptin group (adjusted odds ratio 3·16, 96·2% CI 1·81-5·52; p0·0001). This finding was accompanied by a clinically relevant 0·9% reduction in HbA1c from a baseline of 7·9% with vildagliptin and a between-group difference of -0·6% (98·8% CI -0·81 to -0·33; p0·0001). The overall safety and tolerability was similar in the vildagliptin and placebo groups, with low incidence of hypoglycaemia and no emergence of new safety signals.This study is the first to introduce and show the feasibility of using individualised HbA1c targets as an endpoint in any type 2 diabetes population. Individualised glycaemic target levels are achievable with vildagliptin without any tolerability issues in the elderly type 2 diabetes population.Novartis Pharma AG.
- Published
- 2013
17. Improved glycaemic control with vildagliptin added to insulin, with or without metformin, in patients with type 2 diabetes mellitus
- Author
-
Wolfgang Kothny, James E. Foley, B. Gallwitz, Q. Shao, Valentina Lukashevich, and Plamen Kozlovski
- Subjects
Blood Glucose ,Male ,Pyrrolidines ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Adamantane ,Type 2 diabetes ,Gastroenterology ,law.invention ,Endocrinology ,Randomized controlled trial ,law ,Insulin Secretion ,Insulin ,Medicine ,Vildagliptin ,Aged, 80 and over ,Middle Aged ,Metformin ,Europe ,Treatment Outcome ,Drug Therapy, Combination ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,Asia ,Adolescent ,Placebo ,Drug Administration Schedule ,Double-Blind Method ,Internal medicine ,Diabetes mellitus ,Nitriles ,Internal Medicine ,Humans ,Hypoglycemic Agents ,Aged ,Glycated Hemoglobin ,business.industry ,Body Weight ,Australia ,nutritional and metabolic diseases ,Type 2 Diabetes Mellitus ,Glucose Tolerance Test ,medicine.disease ,United States ,Diabetes Mellitus, Type 2 ,business - Abstract
Aim The aim of this study is to assess the efficacy and safety of vildagliptin 50 mg bid as add-on therapy to insulin in type 2 diabetes mellitus (T2DM). Methods This is a multicentre, double-blind, placebo-controlled, parallel group, clinical trial in T2DM patients inadequately controlled by stable insulin therapy, with or without metformin. Patients received treatment with vildagliptin 50 mg bid or placebo for 24 weeks. Results In all, 449 patients were randomized to vildagliptin (n = 228) or placebo (n = 221). After 24 weeks, the difference in adjusted mean change in haemoglobin A1c (HbA1c) between vildagliptin and placebo was −0.7 ± 0.1% (p
- Published
- 2012
18. One-year safety, tolerability and efficacy of vildagliptin in patients with type 2 diabetes and moderate or severe renal impairment
- Author
-
Per-Henrik Groop, Wolfgang Kothny, Valentina Lukashevich, and Q. Shao
- Subjects
medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,Renal function ,Type 2 diabetes ,Pharmacology ,medicine.disease ,Placebo ,Gastroenterology ,Discontinuation ,law.invention ,Endocrinology ,Randomized controlled trial ,law ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,Medicine ,Vildagliptin ,business ,Adverse effect ,medicine.drug - Abstract
Aim Assess long-term safety and efficacy of the dipeptidlyl peptidase-4 (DPP-4) inhibitor vildagliptin in 369 patients with type 2 diabetes mellitus (T2DM) and moderate or severe renal impairment (RI). Methods Double-blind, randomized, parallel-group, 52-week clinical trial comparing safety and efficacy of vildagliptin (50 mg qd, n = 216) and placebo (n = 153) added to ongoing stable antihyperglycaemic treatment, in patients with T2DM and moderate or severe (glomerular filtration rate [GFR] ≥30 to
- Published
- 2012
19. Trial Logistics, Implementation, and Conduct of the OCTAVE Mega Study in Germany
- Author
-
Rosemarie Kaaden, Wolfgang Kothny, Michael Krekler, Petra Ludwig, and Dagmar Chase
- Subjects
medicine.medical_specialty ,Randomization ,business.industry ,Surgery ,Patient recruitment ,Clinical trial ,Double blind study ,Tolerability ,Drug Discovery ,medicine ,Physical therapy ,Octave ,Enalapril ,Omapatrilat ,business ,medicine.drug - Abstract
Using the example of the largest clinical trial so far conducted to obtain marketing approval (OCTAVE - Omapatrilat Cardiovascular Treatment Assessment Versus Enalapril) this paper describes the way the trial was conducted in Germany and the set-up of the trial logistics. OCTAVE was a prospective, randomised, double-blind study in which the efficacy and tolerability of omapatrilat (CAS 167305-00-2) compared to enalapril (CAS 75847-73-3) were studied in 25 302 patients with uncontrolled blood pressure. Patient recruitment was completed on schedule in just under four months in this global study. An appropriate study design, tailor-made logistics, a special monitoring system and effective project and data management allowed the selection and initiation of 430 study centres in Germany. As a result 4868 patients were randomised within about six months of finalising the study protocol.
- Published
- 2011
20. Clinical experience with vildagliptin in the management of type 2 diabetes in a patient population ≥75 years: a pooled analysis from a database of clinical trials
- Author
-
James E. Foley, Wolfgang Kothny, Q. Shao, Sylvie Dejager, and Anja Schweizer
- Subjects
Male ,medicine.medical_specialty ,Pyrrolidines ,Endocrinology, Diabetes and Metabolism ,Adamantane ,Type 2 diabetes ,Hypoglycemia ,Endocrinology ,Internal medicine ,Diabetes mellitus ,Nitriles ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Vildagliptin ,Adverse effect ,Aged ,Aged, 80 and over ,Glycated Hemoglobin ,Polypharmacy ,Clinical Trials as Topic ,Dipeptidyl-Peptidase IV Inhibitors ,business.industry ,Incidence (epidemiology) ,medicine.disease ,Surgery ,Clinical trial ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,Female ,business ,medicine.drug - Abstract
Aim: To report the experience with vildagliptin in a patient population with type 2 diabetes mellitus (T2DM) ≥75 years. Methods: Efficacy data from seven monotherapy and three add-on therapy to metformin studies, respectively, of ≥24 weeks duration were pooled; effects of 24 weeks of treatment with vildagliptin (50 mg bid) in patients ≥75 years were assessed in these two pooled datasets. Safety data were pooled from 38 studies of ≥12 to ≥104 weeks duration; adverse events (AEs) profiles of vildagliptin (50 mg bid) were evaluated relative to a pool of comparators; 301 patients ≥75 years were analysed. Data in patients
- Published
- 2010
21. Assessing the cardio-cerebrovascular safety of vildagliptin: meta-analysis of adjudicated events from a large Phase III type 2 diabetes population
- Author
-
James E. Foley, Wolfgang Kothny, Anja Schweizer, M. Ligueros-Saylan, A. Couturier, and Sylvie Dejager
- Subjects
Male ,medicine.medical_specialty ,Acute coronary syndrome ,Pyrrolidines ,Endocrinology, Diabetes and Metabolism ,MedDRA ,Population ,Adamantane ,Type 2 diabetes ,Placebo ,Endocrinology ,Internal medicine ,Nitriles ,Internal Medicine ,medicine ,Humans ,Vildagliptin ,education ,Stroke ,Randomized Controlled Trials as Topic ,Dipeptidyl-Peptidase IV Inhibitors ,education.field_of_study ,business.industry ,Middle Aged ,medicine.disease ,Surgery ,Cerebrovascular Disorders ,Clinical Trials, Phase III as Topic ,Diabetes Mellitus, Type 2 ,Relative risk ,Cardiology ,Female ,business ,Diabetic Angiopathies ,medicine.drug - Abstract
Aim: To assess the cardiovascular and cerebrovascular (CCV) safety of the dipeptidyl peptidase-IV inhibitor vildagliptin. Methods: Data were pooled from 25 Phase III studies of vildagliptin, used either as monotherapy or combination therapy, with durations of 12 weeks to ≥ 2 years. The safety of vildagliptin [50 mg qd (N = 1393) or 50 mg bid (N = 6116)] was assessed relative to a pool of all comparators [both placebo and active comparators (N = 6061)]. CCV events were adjudicated in a prospective, blinded fashion by an independent CCV adjudication committee. Meta-analysis of confirmed CCV events was performed with Mantel–Haenszel risk ratios (RRs); categories included in the composite endpoint were acute coronary syndrome, transient ischaemic attack (with imaging evidence of infarction), stroke and CCV death. Subgroup analyses by age (< and ≥ 65 years), gender and cardiovascular (CV) risk status [high CV risk status defined as a previous history of events in the Standard MedDRA Queries of ischaemic heart disease, cardiac failure, ischaemic cerebrovascular conditions and/or embolic/thrombotic events, arterial) were also carried out. In addition, unadjusted and exposure-adjusted incidences are presented for both the composite endpoint and its components. Results: Relative to all comparators, the RRs for the composite endpoint were < 1 for both vildagliptin 50 mg qd [RR = 0.88; 95% CI (0.37, 2.11)] and vildagliptin 50 mg bid [RR = 0.84; 95% CI (0.62, 1.14)]. The results were consistent across subgroups defined by age, gender and CV risk status, including the higher CV risk subgroups of elderly patients [RR for vildagliptin 50 mg bid vs. all comparators = 1.04; 95% CI (0.62, 1.73)], males [RR = 0.87; 95% CI (0.60, 1.24)] or patients with a high CV risk status [RR = 0.78; 95% CI (0.51, 1.19)]. The exposure-adjusted incidences of each component of the composite endpoint for vildagliptin 50 mg bid were also lower than or similar to those of all comparators. Conclusions: In a large meta-analysis, vildagliptin was not associated with an increased risk of adjudicated CCV events relative to all comparators in the broad population of type 2 diabetes including patients at increased risk of CCV events.
- Published
- 2010
22. Vildagliptin as add-on therapy to insulin improves glycemic control without increasing risk of hypoglycemia in Asian, predominantly Chinese, patients with type 2 diabetes mellitus
- Author
-
Guang, Ning, Weiqing, Wang, Ling, Li, Jianhua, Ma, Xiaofeng, Lv, Ming, Yang, Wei, Wang, Michael, Woloschak, Valentina, Lukashevich, and Wolfgang, Kothny
- Subjects
Adult ,Aged, 80 and over ,Blood Glucose ,Glycated Hemoglobin ,Male ,Vildagliptin ,Dipeptidyl-Peptidase IV Inhibitors ,Asia ,Pyrrolidines ,Adolescent ,Adamantane ,Middle Aged ,Hypoglycemia ,Metformin ,Young Adult ,Diabetes Mellitus, Type 2 ,Double-Blind Method ,Nitriles ,Humans ,Hypoglycemic Agents ,Insulin ,Drug Therapy, Combination ,Female ,Aged - Abstract
The aim of the present study was to investigate the efficacy and safety of vildagliptin added onto insulin with or without metformin in an Asian, predominantly Chinese, population with type 2 diabetes mellitus (T2DM).In this 24-week, multicenter, double-blind, placebo-controlled trial, patients with T2DM inadequately controlled (HbA1c 7.5%-11.0%) on stable therapy with long-acting, intermediate-acting, or premixed insulin, with or without concomitant metformin, were randomized to receive vildagliptin 50 mg b.i.d. or placebo.Of 293 patients randomized, 146 received vildagliptin and 147 received placebo treatment. At baseline, the overall mean age of patients was 58.1 years, mean T2DM duration was 11.3 years, and mean HbA1c was 8.7%. The adjusted mean (±SE) change in HbA1c at Week 24 in the vildagliptin and placebo groups was -1.08 ± 0.12% and -0.38 ± 0.12%, respectively (between-treatment difference -0.70 ± 0.16%; P 0.001). The between-group difference in fasting plasma glucose was -0.43 ± 0.38 mmol/L (P = 0.259). Significantly, more patients achieved HbA1c7.0% with vildagliptin than with placebo (23.6% vs. 11.2%; P = 0.006). The incidence of adverse events in the vildagliptin and placebo groups was 43.8% and 46.3%, whereas that of serious adverse events was 3.4% and 6.8%, respectively. The frequency of hypoglycemia was lower in the vildagliptin than placebo group (2.7% vs. 5.4%).The addition of vildagliptin 50 mg b.i.d. significantly improved glycemic control without an increased risk of hypoglycemia in Asian, predominantly Chinese, patients with T2DM inadequately controlled on insulin, with or without metformin.
- Published
- 2015
23. Vildagliptin in patients with type 2 diabetes mellitus and renal impairment
- Author
-
Wolfgang Kothny, Per-Henrik Groop, and Neelesh Dongre
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Pyrrolidines ,Endocrinology, Diabetes and Metabolism ,Adamantane ,Dipeptidyl peptidase-4 inhibitor ,Gastroenterology ,Endocrinology ,Internal medicine ,Diabetes mellitus ,Nitriles ,Internal Medicine ,medicine ,Humans ,In patient ,Vildagliptin ,Renal Insufficiency ,Dipeptidyl-Peptidase IV Inhibitors ,business.industry ,DPP-4 Inhibitors ,Type 2 Diabetes Mellitus ,General Medicine ,medicine.disease ,Diabetes Mellitus, Type 2 ,Creatinine ,Creatinine blood ,business ,medicine.drug - Published
- 2014
24. Vildagliptin added to sulfonylurea improves glycemic control without hypoglycemia and weight gain in Chinese patients with type 2 diabetes mellitus
- Author
-
Wenying, Yang, Xiaoping, Xing, Xiaofeng, Lv, Yiming, Li, Jianhua, Ma, Guoyue, Yuan, Feifei, Sun, Wei, Wang, Michael, Woloschak, Valentina, Lukashevich, Plamen, Kozlovski, Wolfgang, Kothny, and Guangda, Xiang
- Subjects
Adult ,Blood Glucose ,Male ,China ,Pyrrolidines ,Adolescent ,Adamantane ,Weight Gain ,Young Adult ,Double-Blind Method ,Risk Factors ,Nitriles ,Humans ,Hypoglycemic Agents ,Aged ,Aged, 80 and over ,Glycated Hemoglobin ,Vildagliptin ,Dipeptidyl-Peptidase IV Inhibitors ,Middle Aged ,Prognosis ,Hypoglycemia ,Sulfonylurea Compounds ,Diabetes Mellitus, Type 2 ,Glycemic Index ,Case-Control Studies ,Female ,Follow-Up Studies - Abstract
The aim of the present study was to assess the efficacy and safety of vildagliptin as add-on to sulfonylurea therapy in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on sulfonylurea monotherapy.The 24-week randomized double-blind placebo-controlled study compared vildagliptin 50 mg, q.d., with placebo as add-on to glimepiride in T2DM patients who were inadequately controlled (HbA1c 7.5%-11.0% [58-97 mmol/mol]) on a stable dose of sulfonylurea for ≥12 weeks before study entry.In all, 279 patients were randomized to receive either vildagliptin (n = 143) or placebo (n = 136). At baseline, overall mean age was 58.5 years, body weight 68.1 kg, duration of diabetes 6.9 years and daily glimepiride dose 3.3 mg. After 24 weeks, the adjusted mean change (AMΔ) in HbA1c was -0.7% (-8 mmol/mol; baseline 8.6%, 70 mmol/mol) in the vildagliptin group and -0.2% (-2 mmol/mol; baseline 8.7%, 72 mmol/mol) in the placebo group, with a treatment difference of -0.5% (-5 mmol/mol; P 0.001). The between-group difference in AMΔ in fasting plasma glucose was -0.4 mmol/L (P = 0.160). There was a slight, but not significant, decrease in body weight in both groups. No hypoglycemic events were reported in either group, including those patients reaching HbA1c7.0%. Patients in the vildagliptin and placebo groups reported low and comparable incidences of adverse events (14.0% vs. 17.8%) and serious adverse events (0.7% in each group).Vildagliptin 50 mg, q.d., added to sulfonylurea monotherapy is effective in Chinese patients with T2DM, without increasing the risk of hypoglycemia and weight gain.
- Published
- 2014
25. Efficacy and safety of vildagliptin in patients with type 2 diabetes mellitus inadequately controlled with dual combination of metformin and sulphonylurea
- Author
-
Valentina Lukashevich, Wolfgang Kothny, S. Del Prato, and M. Araga
- Subjects
Blood Glucose ,Male ,Pyrrolidines ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Adamantane ,Type 2 diabetes ,Pharmacology ,Gastroenterology ,Endocrinology ,Vildagliptin ,glimepiride ,Aged, 80 and over ,Middle Aged ,Metformin ,Treatment Outcome ,oral antidiabetic drug ,Drug Therapy, Combination ,Female ,type 2 diabetes ,medicine.symptom ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,Hypoglycemia ,Placebo ,Drug Administration Schedule ,Double-Blind Method ,Internal medicine ,Nitriles ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,DPP-4 inhibitor ,Aged ,Glycated Hemoglobin ,Dipeptidyl-Peptidase IV Inhibitors ,business.industry ,Body Weight ,nutritional and metabolic diseases ,Type 2 Diabetes Mellitus ,Original Articles ,medicine.disease ,Glimepiride ,Sulfonylurea Compounds ,Diabetes Mellitus, Type 2 ,business ,Weight gain - Abstract
Aim The broadly used combination of metformin and sulphonylurea (SU) often fails to bring patients to glycaemic goal. This study assessed the efficacy and safety of vildagliptin as add-on therapy to metformin plus glimepiride combination in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycaemic control. Methods A multicentre, double-blind, placebo-controlled study randomized patients to receive treatment with vildagliptin 50 mg bid (n = 158) or placebo (n = 160) for 24 weeks. Results After 24 weeks, the adjusted mean change in haemoglobin A1c (HbA1c) was −1.01% with vildagliptin (baseline 8.75%) and −0.25% with placebo (baseline 8.80%), with a between-treatment difference of −0.76% (p
- Published
- 2014
26. Effect of Oral Postmenopausal Hormone Replacement on Progression of Atherosclerosis
- Author
-
Stefan Störk, Philip Schmitt, Peter Angerer, Clemens von Schacky, and Wolfgang Kothny
- Subjects
Carotid Artery Diseases ,medicine.medical_specialty ,Norpregnenes ,Myocardial Infarction ,Gestodene ,Fibrinogen ,law.invention ,Randomized controlled trial ,Risk Factors ,law ,Internal medicine ,medicine ,Humans ,cardiovascular diseases ,Myocardial infarction ,Estradiol ,Vascular disease ,business.industry ,Estrogen Replacement Therapy ,medicine.disease ,Tunica intima ,Surgery ,Clinical trial ,Menopause ,Carotid Arteries ,medicine.anatomical_structure ,cardiovascular system ,Cardiology ,Female ,Tunica Intima ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
Abstract —Postmenopausal hormone replacement therapy (HRT) is associated with low cardiovascular morbidity and mortality in epidemiological studies. Yet, no randomized trial has examined whether HRT is effective for prevention of coronary heart disease (CHD) in women with increased risk. The objective of this study was to determine whether HRT can slow progression of atherosclerosis, measured as intima-media thickness (IMT) in carotid arteries. Carotid IMT is an appropriate intermediate end point to investigate clinically relevant effects on atherogenesis. This randomized, controlled, observer-blind, clinical, single-center trial enrolled 321 healthy postmenopausal women with increased IMT in ≥1 segment of the carotid arteries. For a period of 48 weeks, subjects received either 1 mg/d 17β-estradiol continuously plus 0.025 mg gestodene for 12 days every month (standard-progestin group), or 1 mg 17β-estradiol plus 0.025 mg gestodene for 12 days every third month (low-progestin group), or no HRT. Maximum IMT in 6 carotid artery segments (common, bifurcation, and internal, both sides) was measured by B-mode ultrasound before and after intervention. HRT did not slow IMT progression in carotid arteries. Mean maximum IMT in the carotid arteries increased by 0.02±0.05 mm in the no HRT group and by 0.03±0.05 and 0.03±0.05 mm, respectively, in the HRT groups ( P >0.2). HRT significantly decreased LDL cholesterol, fibrinogen, and follicle-stimulating hormone. In conclusion, 1 year of HRT was not effective in slowing progression of subclinical atherosclerosis in postmenopausal women at increased risk.
- Published
- 2001
27. Clinical evidence and mechanistic basis for vildagliptin's effect in combination with insulin
- Author
-
Anja, Schweizer, James E, Foley, Wolfgang, Kothny, and Bo, Ahrén
- Subjects
Blood Glucose ,Glycated Hemoglobin ,Vildagliptin ,Dipeptidyl-Peptidase IV Inhibitors ,GIP ,Pyrrolidines ,endocrine system diseases ,nutritional and metabolic diseases ,Adamantane ,Review ,Weight Gain ,Hypoglycemia ,incretin ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,DPP-4 ,insulin therapy ,Nitriles ,Humans ,Hypoglycemic Agents ,Insulin ,Drug Therapy, Combination ,type 2 diabetes ,GLP-1 ,Biomarkers - Abstract
Due to the progressive nature of type 2 diabetes, many patients need insulin as add-on to oral antidiabetic drugs (OADs) in order to maintain adequate glycemic control. Insulin therapy primarily targets elevated fasting glycemia but is less effective to reduce postprandial hyperglycemia. In addition, the risk of hypoglycemia limits its effectiveness and there is a concern of weight gain. These drawbacks may be overcome by combining insulin with incretin-based therapies as these increase glucose sensitivity of both the α- and β-cells, resulting in improved postprandial glycemia without the hypoglycemia and weight gain associated with increasing the dose of insulin. The dipeptidyl peptidase-IV (DPP-4) inhibitor vildagliptin has also been shown to protect from hypoglycemia by enhancing glucagon counterregulation. The effectiveness of combining vildagliptin with insulin was demonstrated in three different studies in which vildagliptin decreased A1C levels when added to insulin therapy without increasing hypoglycemia. This was established with and without concomitant metformin therapy. Furthermore, the effectiveness of vildagliptin appears to be greater when insulin is used as a basal regimen as opposed to being used to reduce postprandial hyperglycemia, since improvement in insulin secretion likely plays a minor role when relatively high doses of insulin are administered before meals. This article reviews the clinical experience with the combination of vildagliptin and insulin and discusses the mechanistic basis for the beneficial effects of the combination. The data support the use of vildagliptin in combination with insulin in general and, in line with emerging clinical practice, suggest that treating patients with vildagliptin, metformin, and basal insulin could be an attractive therapeutic option.
- Published
- 2013
28. Safety and efficacy of vildagliptin versus placebo in patients with type 2 diabetes and moderate or severe renal impairment: a prospective 24-week randomized placebo-controlled trial
- Author
-
Anja Schweizer, Q. Shao, Per-Henrik Groop, Valentina Lukashevich, and Wolfgang Kothny
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pyrrolidines ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Placebo-controlled study ,Adamantane ,Type 2 diabetes ,Pharmacology ,Placebo ,Gastroenterology ,law.invention ,Young Adult ,Endocrinology ,Randomized controlled trial ,Double-Blind Method ,law ,Internal medicine ,Nitriles ,Internal Medicine ,medicine ,Humans ,Vildagliptin ,Diabetic Nephropathies ,Prospective Studies ,Prospective cohort study ,Aged ,Aged, 80 and over ,Glycated Hemoglobin ,Dipeptidyl-Peptidase IV Inhibitors ,business.industry ,Middle Aged ,medicine.disease ,Discontinuation ,Treatment Outcome ,Tolerability ,Diabetes Mellitus, Type 2 ,Kidney Failure, Chronic ,Female ,business ,medicine.drug - Abstract
Aim: Assess safety/tolerability and efficacy of the DPP-4 inhibitor vildagliptin in 515 patients with type 2 diabetes mellitus (T2DM) and moderate or severe renal impairment (RI). Methods: Double-blind, randomized, parallel-group, placebo-controlled, 24-week clinical trial assessing safety and efficacy of vildagliptin (50 mg qd) added to current antidiabetic therapy, in patients with T2DM and moderate or severe RI (GFR ≥ 30 to
- Published
- 2011
29. An assessment of adverse effects of vildagliptin versus comparators on the liver, the pancreas, the immune system, the skin and in patients with impaired renal function from a large pooled database of Phase II and III clinical trials
- Author
-
James E. Foley, A. Couturier, Anja Schweizer, Wolfgang Kothny, and M. Ligueros-Saylan
- Subjects
Male ,medicine.medical_specialty ,Pyrrolidines ,Bilirubin ,Endocrinology, Diabetes and Metabolism ,Adamantane ,Type 2 diabetes ,Gastroenterology ,chemistry.chemical_compound ,Endocrinology ,Risk Factors ,Internal medicine ,Nitriles ,Internal Medicine ,medicine ,Confidence Intervals ,Humans ,Hypoglycemic Agents ,Vildagliptin ,Diabetic Nephropathies ,Adverse effect ,Pancreas ,Dipeptidyl peptidase-4 ,Aged ,Skin ,Clinical Trials as Topic ,Dipeptidyl-Peptidase IV Inhibitors ,business.industry ,Odds ratio ,medicine.disease ,Confidence interval ,chemistry ,Diabetes Mellitus, Type 2 ,Liver ,Immune System ,Pancreatitis ,Female ,business ,medicine.drug - Abstract
Aim: To assess the safety of vildagliptin versus all comparators (ACs) with regard to organs, systems or tissues of particular interest in type 2 diabetes (T2DM) and areas of potential concern with dipeptidyl peptidase-IV (DPP-4) inhibitors. Methods: Data were pooled from 38 studies where vildagliptin was given for ≥12 to > 104 weeks in patients with T2DM. Absolute and exposure-adjusted incidence rates and Peto odds ratios (ORs) versus ACs with corresponding 95% confidence intervals (CI) were calculated. Results: There were > 7000 subject-years of exposure (SYE) to vildagliptin 50 mg bid and > 6500 SYE to ACs. For mild hepatic enzyme elevations with and without elevated bilirubin levels, the ORs for vildagliptin 50 mg bid were 1.24 (95% CI: [0.80, 1.93]) and 1.19 (95% CI: [0.29, 4.90]), respectively. The exposure-adjusted incidences of markedly elevated hepatic enzymes and for enzyme elevations with bilirubin ≥ 2× ULN with vildagliptin 50 mg bid were ≤ those in the ACs group. For hepatic and pancreatitis-related AEs, the ORs for vildagliptin 50 mg bid were 0.87 (95% CI: [0.64, 1.19]) and 0.70 (95% CI: [0.26, 1.88]), respectively, and for any AE in the infections and infestations SOC, this was 1.04 (95% CI: [0.96, 1.13]). The incidences of skin-related AEs were low and the risk with vildagliptin 50 mg bid was not significantly different from ACs [(OR = 1.10 (95% CI: [0.80, 1.51])]. Conclusions: The present meta-analyses indicate that vildagliptin was not associated with increased risk of hepatic events or hepatic enzyme elevations indicative of drug-induced liver injury, pancreatitis, infections or skin-related toxicity.
- Published
- 2010
30. Trial logistics, implementation, and conduct of the OCTAVE mega study in Germany. Prospective, randomised, double-blind study to compare the efficacy and tolerability of omapatrilat and enalapril
- Author
-
Wolfgang, Kothny, Rosemarie, Kaaden, Petra, Ludwig, Dagmar, Chase, and Michael, Krekler
- Subjects
Double-Blind Method ,Enalapril ,Pyridines ,Research Design ,Thiazepines ,Data Collection ,Surveys and Questionnaires ,Hypertension ,Humans ,Angiotensin-Converting Enzyme Inhibitors ,Prospective Studies ,Antihypertensive Agents - Abstract
Using the example of the largest clinical trial so far conducted to obtain marketing approval (OCTAVE--Omapatrilat Cardiovascular Treatment Assessment Versus Enalapril) this paper describes the way the trial was conducted in Germany and the set-up of the trial logistics. OCTAVE was a prospective, randomised, double-blind study in which the efficacy and tolerability of omapatrilat (CAS 167305-00-2) compared to enalapril (CAS 75847-73-3) were studied in 25 302 patients with uncontrolled blood pressure. Patient recruitment was completed on schedule in just under four months in this global study. An appropriate study design, tailor-made logistics, a special monitoring system and effective project and data management allowed the selection and initiation of 430 study centres in Germany. As a result 4868 patients were randomised within about six months of finalising the study protocol.
- Published
- 2004
31. Effect of dietary supplementation with omega-3 fatty acids on progression of atherosclerosis in carotid arteries
- Author
-
Clemens von Schacky, Wolfgang Kothny, Stefan Störk, and Peter Angerer
- Subjects
Carotid Artery Diseases ,Male ,medicine.medical_specialty ,Physiology ,Diet therapy ,Coronary Disease ,Coronary artery disease ,Fish Oils ,Double-Blind Method ,Physiology (medical) ,Internal medicine ,Fatty Acids, Omega-3 ,medicine ,Humans ,Prospective Studies ,Treatment Failure ,Prospective cohort study ,Aged ,Ultrasonography ,chemistry.chemical_classification ,Vascular disease ,business.industry ,Middle Aged ,Fish oil ,medicine.disease ,Coronary Vessels ,Surgery ,Coronary arteries ,medicine.anatomical_structure ,Carotid Arteries ,Intima-media thickness ,chemistry ,Dietary Supplements ,Cardiology ,Disease Progression ,Female ,Cardiology and Cardiovascular Medicine ,business ,Tunica Intima ,Polyunsaturated fatty acid - Abstract
Objective: Omega-3 polyunsaturated fatty acids (ω-3 PUFA) from fish oil slow atherosclerosis progression in coronary arteries, as we showed in a randomized double-blind placebo-controlled clinical trial. Embedded in this trial, the present study examined the influence of 2 years of dietary supplementation with 1.65 g ω-3 PUFA per day on progression of carotid atherosclerosis in 223 patients with coronary artery disease. Methods: Coronary angiography, a comprehensive clinical examination, and intima-media thickness measurement by B-mode ultrasound of the carotid arteries (common, internal and bifurcation), were performed at the study start and study end. An expert panel visually evaluated the global change of carotid atherosclerosis on a semiquantitative scale. A second outcome measure was the change of overall mean maximum intima-media thickness. Results: One hundred and seventy-one patients completed the study. In the global change score, 38% of the patients in the fish oil group and 35% in the placebo group showed progression. Global change was not different between intervention groups. Mean maximum intima-media thickness increased by 0.07±0.13 mm and 0.05±0.11 mm in the fish oil and placebo group, respectively (mean±S.D., P =0.24). No correlation was found between the change in carotid and coronary arteries. Conclusions: In this group of selected patients with documented coronary artery disease ω-3 PUFA given for 2 years did not demonstrate an effect on slowing progression of atherosclerosis in carotid arteries as measured by ultrasound.
- Published
- 2002
32. Effect of postmenopausal hormone replacement on atherosclerosis in femoral arteries
- Author
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Clemens von Schacky, Wolfgang Kothny, Stefan Störk, and Peter Angerer
- Subjects
medicine.medical_specialty ,genetic structures ,Hormone Replacement Therapy ,Norpregnenes ,medicine.medical_treatment ,Urology ,Femoral artery ,Coronary Artery Disease ,Gestodene ,General Biochemistry, Genetics and Molecular Biology ,Follicle-stimulating hormone ,medicine.artery ,medicine ,Humans ,Triglycerides ,Ultrasonography ,Progestogen ,Estradiol ,business.industry ,Vascular disease ,Cholesterol, HDL ,Obstetrics and Gynecology ,Fibrinogen ,Hormone replacement therapy (menopause) ,Cholesterol, LDL ,Middle Aged ,medicine.disease ,eye diseases ,Surgery ,Menopause ,Femoral Artery ,Carotid Arteries ,Cholesterol ,Intima-media thickness ,Female ,sense organs ,Follicle Stimulating Hormone ,business ,Tunica Intima ,medicine.drug - Abstract
Objecties: On the basis of epidemiological and experimental data, it has been supposed that hormone replacement therapy (HRT) inhibits atherosclerosis in postmenopausal women. This randomized controlled trial examined whether 1 mg 17-estradiol daily, combined cyclically with 0.025 mg gestodene in every month (HRT 1), or in every third month (HRT 2) slows the increase of intima-media thickness in femoral arteries compared with no HRT. Methods: Healthy postmenopausal women (n=321) with an increased risk for future vascular disease as indicated by 1 mm of intima-media thickness in the carotid arteries were equally randomized to one of the three groups for 48 weeks. Ultrasound scans of femoral arteries were recorded at study start and study end, together with a thorough clinical examination and laboratory work-up. Results: Complete scans were obtained in 260 of the 264 subjects who participated until study end. Mean maximum intima-media thickness of four femoral artery segments (common and superficial, both sides) was 0.930.37 mm (meanS.D.) at study start. It increased by 0.02 0.05, 0.02 0.05, and 0.030.05 mm in the HRT 1, HRT 2 and no HRT groups, respectively (HRT 1 versus no HRT, HRT 2 versus no HRT; both P0.2). Compared with no HRT, HRT significantly lowered follicle stimulating hormone, low-density lipoprotein cholesterol, and fibrinogen. Conclusions: In this 1-year trial, irrespective of the progestogen dose used, HRT with 1 mg 17-estradiol did not inhibit progression of femoral artery atheroslerosis in postmenopausal women with subclinical vascular disease. © 2002 Elsevier Science Ireland Ltd. All rights reserved.
- Published
- 2002
33. Vildagliptin in renal impairment
- Author
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Neelesh Dongre and Wolfgang Kothny
- Subjects
Nephrology ,medicine.medical_specialty ,business.industry ,Type 2 Diabetes Mellitus ,medicine.disease ,Nephropathy ,Diabetes Mellitus, Type 2 ,Hyperglycemia ,Relative risk ,Internal medicine ,medicine ,Humans ,Hypoglycemic Agents ,media_common.cataloged_instance ,Diabetic Nephropathies ,Vildagliptin ,European union ,Summary of Product Characteristics ,Intensive care medicine ,business ,media_common ,medicine.drug ,Glycemic - Abstract
We read with interest the article by Schernthaner and Schernthaner [1] entitled ‘‘Diabetic nephropathy: new approaches for improving glycemic control and reducing risk’’, published in the November/December 2013 edition of J Nephrol. While we commend the authors for highlighting this important topic, we are writing to draw attention to what we believe is potentially misleading information regarding the dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin (Galvus ) in this article. The authors state ‘‘Vildagliptin is not recommended for patients with moderate or severe renal impairment ... because of a scarcity of evidence in this setting’’, citing an earlier paper by Scheen [2]. Although Schernthaner and Schernthaner faithfully quote Dr. Scheen, neither article accurately represents the current labelling for vildagliptin, approved in the European Union and elsewhere, relating to its use in renal impairment. In fact, the Galvus Summary of Product Characteristics [3] states that vildagliptin may be used at the standard dosage (i.e. 50 mg twice daily) in patients with mild renal impairment (CrCl C50 ml/min), and that the recommended dosage for patients with moderate to severe renal impairment, or with end-stage renal disease, is 50 mg once daily. We are concerned that the authors’ statement may lead physicians to either avoid initiating vildagliptin in patients who could potentially benefit from treatment, or, because of unfounded safety concerns, to unnecessarily alter medication in patients who are responding well to vildagliptin. We believe vildagliptin is an effective treatment option for patients with type 2 diabetes mellitus, and has a favorable benefit:risk ratio in patients with renal impairment when used in accordance with the product labelling.
- Published
- 2014
34. Bone sialoprotein is a specific biochemical marker of bone metabolism in postmenopausal women: a randomized 1-year study
- Author
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U. Wehr, Stefan Störk, C. Störk, P. Schmitt, Peter Angerer, Wolfgang Kothny, C. von Schacky, and W. A. Rambeck
- Subjects
Bone sialoprotein ,medicine.medical_specialty ,Deoxypyridinoline ,Pyridines ,Endocrinology, Diabetes and Metabolism ,Sialoglycoproteins ,Osteocalcin ,Bone resorption ,Bone and Bones ,Bone remodeling ,chemistry.chemical_compound ,stomatognathic system ,N-terminal telopeptide ,Reference Values ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Bone Resorption ,Aged ,Pyridinoline ,biology ,business.industry ,Estrogen Replacement Therapy ,Middle Aged ,Alkaline Phosphatase ,Resorption ,Postmenopause ,Endocrinology ,chemistry ,biology.protein ,Alkaline phosphatase ,Female ,sense organs ,business ,Biomarkers - Abstract
Accelerated bone remodeling after the menopause is associated with increased bone loss that can be abolished using hormone replacement therapy (HRT). Biochemical markers of bone metabolism are known to correlate closely with changes in bone histomorphometry and osteodensitometry. Bone sialoprotein (BSP), a major constituent of bone matrix, is almost exclusively found in mineralized tissues and therefore considered a potential marker of bone metabolism. In 82 postmenopausal women, randomly allocated to either low-dose sequential HRT or no HRT, serum BSP was measured and compared with established specific biochemical markers of bone resorption [urinary deoxypyridinoline (DPD), pyridinoline (PYD) and amino-terminal telopeptide (NTx)] and markers of bone formation [serum osteocalcin (Oc) and bone-specific alkaline phosphatase (bALP)]. Longitudinal analysis showed a marked response of BSP levels following commencement of HRT, resulting in a 52% reduction after 12 months compared with initial values. The changes of BSP levels over time were at least as strong as in conventional markers of bone formation and resorption and paralleled their changes. A moderate to close correlation was found between BSP and both markers of bone resorption (r = 0.57 for NTx; r = 0.38 for DPD) and formation (r = 0.55 for Oc; r = 0.39 for bALP; p0.0001, respectively). Our data demonstrate a cause and effect relationship between commencement of HRT and a change in serum BSP. In conclusion, serum BSP circumvents some of the limitations of urinary measurements and appears valuable for the quantitative monitoring of the skeletal response to HRT in healthy postmenopausal women.
- Published
- 2001
35. Impact of social support, cynical hostility and anger expression on progression of coronary atherosclerosis
- Author
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Clemens von Schacky, Wolfgang Kothny, Dagmar Mühlbauer, Harald Mudra, Peter Angerer, and Uwe Siebert
- Subjects
Male ,medicine.medical_specialty ,Cost effectiveness ,media_common.quotation_subject ,Hostility ,Coronary Disease ,Anger ,Coronary Angiography ,Coronary artery disease ,Social support ,Medicine ,Humans ,Prospective Studies ,Risk factor ,Prospective cohort study ,media_common ,business.industry ,Social Support ,Odds ratio ,Middle Aged ,medicine.disease ,Surgery ,Logistic Models ,Disease Progression ,Female ,medicine.symptom ,business ,Cardiology and Cardiovascular Medicine ,Clinical psychology - Abstract
OBJECTIVES This prospective cohort study of patients with coronary artery disease (CAD) sought to determine the impact of social support, anger expression and cynical hostility on progression of coronary atherosclerosis as shown by angiography. BACKGROUND Low social support, high levels of expressed anger and cynical hostility are correlated to increased CAD morbidity and mortality. However, the impact of these factors, alone or together, on progression of human coronary atherosclerosis is unknown. METHODS Of 223 patients with CAD documented by standardized angiography at baseline, 162 had a second angiogram after two years. An expert panel who had no knowledge of the patients' characteristics evaluated the films pairwise to determine disease progression. At baseline, all patients were asked to answer three self-report questionnaires: questions concerning emotional social support, the State-Trait-Anger-Expression Inventory (STAXI) and the Cook-Medley cynical hostility scale. Each patient's clinical and laboratory status was followed. RESULTS Questionnaires and angiographic follow-up data were available for 150 patients. Bivariate analysis of the psychological variables showed a higher risk of progression only for patients who scored high on STAXI anger-out or low on social support. In the multivariate analysis, when adjusting for confounding variables and examining the interaction between psychological variables, only patients with both high anger-out and low social support were at highly increased risk for progression (odds ratio 30, confidence interval [CI] 5.5 to 165.1; RR 3.19). CONCLUSIONS Patients with CAD and low emotional social support who express anger outwardly are at a highly increased risk of disease progression, independent of medication or other risk factors.
- Published
- 2000
36. Short term effects of omega-3 fatty acids on the radial artery of patients with coronary artery disease
- Author
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Clemens von Schacky, Wolfgang Kothny, Stefan Störk, and Peter Angerer
- Subjects
Male ,medicine.medical_specialty ,Vasodilation ,Coronary Disease ,Coronary artery disease ,Double-Blind Method ,Internal medicine ,medicine.artery ,Fatty Acids, Omega-3 ,Medicine ,Humans ,Radial artery ,Aged ,business.industry ,Reproducibility of Results ,Middle Aged ,Fish oil ,medicine.disease ,Eicosapentaenoic acid ,Dietary Fats ,Surgery ,Blood pressure ,Docosahexaenoic acid ,Dietary Supplements ,Radial Artery ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,Flow-Mediated Vasodilation - Abstract
Long-term dietary v-3 fatty acids improve coronary endothelial function in CAD patients, heart transplant recipients and diabetics. This study assessed whether short term v-3 fatty acids affect radial artery function in CAD patients. A high resolution A-mode echotracking device (NIUS 02) was used to measure continuously, radial artery internal diameter at rest, during flow mediated vasodilation (FMD), during cold pressure test (CPT), and after sublingual glyceryl trinitrate (GTN). We studied 18 male CAD patients in a randomized, double blind, placebo controlled design. Between pre- and post-intervention measurements 24 h apart, nine subjects received 18 g fish oil concentrate (6.4 g eicosapentaenoic acid and 3.9 g docosahexaenoic acid) and nine subjects 18 g placebo. In the placebo group correlation between both baseline diameters was 0.98; PB 0.001. Pre-intervention FMD was 7.595.6%, CPT mediated vasoconstriction was 3.89 2.5%, and GTN induced vasodilation was 15.79 9.8%. Vascular responses post-intervention showed no significant difference to pre intervention, there was no significant difference between both treatment groups. The radial artery does not seem to be an immediate target for vasodilatory actions of v-3 fatty acids. © 1998 Elsevier Science Ireland Ltd. All rights reserved.
- Published
- 1998
37. Clinical evidence and mechanistic basis for vildagliptin's effect in combination with insulin
- Author
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James E. Foley, Bo Ahrén, Wolfgang Kothny, and Anja Schweizer
- Subjects
medicine.medical_specialty ,endocrine system diseases ,business.industry ,Endocrinology, Diabetes and Metabolism ,Insulin ,medicine.medical_treatment ,Public Health, Environmental and Occupational Health ,nutritional and metabolic diseases ,Incretin ,Hematology ,General Medicine ,Type 2 diabetes ,Hypoglycemia ,medicine.disease ,Metformin ,Postprandial ,Endocrinology ,Basal (medicine) ,Internal medicine ,Medicine ,Pharmacology (medical) ,Vildagliptin ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
Due to the progressive nature of type 2 diabetes, many patients need insulin as add-on to oral antidiabetic drugs (OADs) in order to maintain adequate glycemic control. Insulin therapy primarily targets elevated fasting glycemia but is less effective to reduce postprandial hyperglycemia. In addition, the risk of hypoglycemia limits its effectiveness and there is a concern of weight gain. These drawbacks may be overcome by combining insulin with incretin-based therapies as these increase glucose sensitivity of both the α- and β-cells, resulting in improved postprandial glycemia without the hypoglycemia and weight gain associated with increasing the dose of insulin. The dipeptidyl peptidase-IV (DPP-4) inhibitor vildagliptin has also been shown to protect from hypoglycemia by enhancing glucagon counterregulation. The effectiveness of combining vildagliptin with insulin was demonstrated in three different studies in which vildagliptin decreased A1C levels when added to insulin therapy without increasing hypoglycemia. This was established with and without concomitant metformin therapy. Furthermore, the effectiveness of vildagliptin appears to be greater when insulin is used as a basal regimen as opposed to being used to reduce postprandial hyperglycemia, since improvement in insulin secretion likely plays a minor role when relatively high doses of insulin are administered before meals. This article reviews the clinical experience with the combination of vildagliptin and insulin and discusses the mechanistic basis for the beneficial effects of the combination. The data support the use of vildagliptin in combination with insulin in general and, in line with emerging clinical practice, suggest that treating patients with vildagliptin, metformin, and basal insulin could be an attractive therapeutic option.
- Published
- 2013
38. Vildagliptin-insulin combination improves glycemic control in Asians with type 2 diabetes
- Author
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Plamen Kozlovski, James E. Foley, Q. Shao, Valentina Lukashevich, and Wolfgang Kothny
- Subjects
medicine.medical_specialty ,Brief Article ,endocrine system diseases ,business.industry ,Endocrinology, Diabetes and Metabolism ,Insulin ,medicine.medical_treatment ,nutritional and metabolic diseases ,Type 2 diabetes ,Hypoglycemia ,medicine.disease ,Placebo ,Gastroenterology ,Metformin ,Endocrinology ,Tolerability ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,Medicine ,Vildagliptin ,business ,medicine.drug - Abstract
AIM: To assess the efficacy and safety of vildagliptin 50 mg bid as add-on therapy to insulin in Asian patients with type 2 diabetes mellitus (T2DM). METHODS: This was a post hoc analysis of a subgroup of Asian patients from a multicenter, randomized, double-blind, placebo-controlled, parallel-group study in T2DM patients inadequately controlled by stable insulin therapy, with or without metformin. A total of 173 patients were randomized 1:1 to receive treatment with vildagliptin 50 mg bid (n = 87) or placebo (n = 86) for 24 wk. Changes in HbA1c and fasting plasma glucose (FPG), from baseline to study endpoint, were analyzed using an analysis of covariance model. Change from baseline to endpoint in body weight was summarized by treatment. Safety and tolerability of vildagliptin was also evaluated. RESULTS: After 24 wk, the difference in adjusted mean change in HbA1c between vildagliptin and placebo was 0.82% (8.96 mmol/mol; P < 0.001) in Asian subgroup, 0.85% (9.29 mmol/mol; P < 0.001) in patients also receiving metformin, and 0.73% (7.98 mmol/mol; P < 0.001) in patients without metformin, all in favor of vildagliptin. There was no significant difference in the change in FPG between treatments. Weight was stable in both treatment groups (+0.3 kg and -0.2 kg, for vildagliptin and placebo, respectively). Overall, vildagliptin was safe and well tolerated with similarly low incidences of hypoglycemia (8.0% vs 8.1%) and no severe hypoglycemic events were experienced in either group. CONCLUSION: In Asian patients inadequately controlled with insulin (with or without concomitant metformin), insulin-vildagliptin combination treatment significantly reduced HbA1c compared with placebo, without an increase in risk of hypoglycemia or weight gain.
- Published
- 2013
39. Assessing the general safety and tolerability of vildagliptin: value of pooled analyses from a large safety database versus evaluation of individual studies
- Author
-
Sylvie Dejager, James E. Foley, Wolfgang Kothny, and Anja Schweizer
- Subjects
safety ,dipeptidyl peptidase-4 ,Pyrrolidines ,Time Factors ,Databases, Factual ,Endocrinology, Diabetes and Metabolism ,Adamantane ,Hypoglycemia ,computer.software_genre ,Placebo ,Risk Assessment ,Clinical Trials, Phase II as Topic ,Risk Factors ,Nitriles ,Odds Ratio ,medicine ,Humans ,Hypoglycemic Agents ,Pharmacology (medical) ,Vildagliptin ,Adverse effect ,Original Research ,Dipeptidyl-Peptidase IV Inhibitors ,Evidence-Based Medicine ,Database ,business.industry ,Public Health, Environmental and Occupational Health ,Hematology ,General Medicine ,Odds ratio ,medicine.disease ,Vascular Health and Risk Management ,Clinical trial ,Treatment Outcome ,Clinical Trials, Phase III as Topic ,Diabetes Mellitus, Type 2 ,Tolerability ,Consumer Product Safety ,type 2 diabetes ,Cardiology and Cardiovascular Medicine ,Risk assessment ,business ,edema ,computer ,medicine.drug - Abstract
Anja Schweizer1, Sylvie Dejager2, James E Foley3, Wolfgang Kothny31Novartis Pharma AG, Basel, Switzerland; 2Novartis Pharma SAS, Rueil-Malmaison, France; 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, USAAim: Analyzing safety aspects of a drug from individual studies can lead to difficult-to-interpret results. The aim of this paper is therefore to assess the general safety and tolerability, including incidences of the most common adverse events (AEs), of vildagliptin based on a large pooled database of Phase II and III clinical trials.Methods: Safety data were pooled from 38 studies of ≥12 to ≥104 weeks' duration. AE profiles of vildagliptin (50 mg bid; N = 6116) were evaluated relative to a pool of comparators (placebo and active comparators; N = 6210). Absolute incidence rates were calculated for all AEs, serious AEs (SAEs), discontinuations due to AEs, and deaths.Results: Overall AEs, SAEs, discontinuations due to AEs, and deaths were all reported with a similar frequency in patients receiving vildagliptin (69.1%, 8.9%, 5.7%, and 0.4%, respectively) and patients receiving comparators (69.0%, 9.0%, 6.4%, and 0.4%, respectively), whereas drug-related AEs were seen with a lower frequency in vildagliptin-treated patients (15.7% vs 21.7% with comparators). The incidences of the most commonly reported specific AEs were also similar between vildagliptin and comparators, except for increased incidences of hypoglycemia, tremor, and hyperhidrosis in the comparator group related to the use of sulfonylureas.Conclusions: The present pooled analysis shows that vildagliptin was overall well tolerated in clinical trials of up to >2 years in duration. The data further emphasize the value of a pooled analysis from a large safety database versus assessing safety and tolerability from individual studies.Keywords: type 2 diabetes, dipeptidyl peptidase-4, edema, safety, vildagliptin
- Published
- 2011
40. The Effect of Dietary ω-3 Fatty Acids on Coronary Atherosclerosis
- Author
-
Harald Mudra, Wolfgang Kothny, C. von Schacky, Karl Theisen, and Peter Angerer
- Subjects
Adult ,Male ,medicine.medical_specialty ,Placebo-controlled study ,Coronary Artery Disease ,Coronary Angiography ,Placebo ,Gastroenterology ,Statistics, Nonparametric ,law.invention ,Placebos ,Coronary artery disease ,chemistry.chemical_compound ,Randomized controlled trial ,law ,Internal medicine ,Fatty Acids, Omega-3 ,Internal Medicine ,medicine ,Humans ,Coronary atherosclerosis ,Cholesterol ,business.industry ,Cholesterol, LDL ,General Medicine ,Middle Aged ,medicine.disease ,Fish oil ,Surgery ,chemistry ,Docosahexaenoic acid ,Disease Progression ,Patient Compliance ,Female ,business - Abstract
Background Epidemiologic studies, studies of mechanisms of action, and many animal studies indicate that dietary intake of omega-3 fatty acids has antiatherosclerotic potential. Few trials in humans have examined this potential. Objective To determine the effect of dietary intake of omega-3 fatty acids on the course of coronary artery atherosclerosis in humans. Design Randomized, double-blind, placebo-controlled, clinically controlled trial. Setting University preventive cardiology unit. Patients 223 patients with angiographically proven coronary artery disease. Intervention Fish oil concentrate (55% eicosapentaenoic and docosahexaenoic acids) or a placebo with a fatty acid composition resembling that of the average European diet, 6 g/d for 3 months and then 3 g/d for 21 months. Measurements The results of standardized coronary angiography, done before and after 2 years of treatment, were evaluated by an expert panel (primary end point) and by quantitative coronary angiography. Patients were followed for clinical and laboratory status. Results Pairs of angiograms (one taken at baseline and one taken at 2 years) were evaluated for 80 of 112 placebo recipients and 82 of 111 fish oil recipients. At the end of treatment, 48 coronary segments in the placebo group showed changes (36 showed mild progression, 5 showed moderate progression, and 7 showed mild regression) and 55 coronary segments in the fish oil group showed changes (35 showed mild progression, 4 showed moderate progression, 14 showed mild regression, and 2 showed moderate regression) (P = 0.041). Loss in minimal luminal diameter, as assessed by quantitative coronary angiography, was somewhat less in the fish oil group (P > 0.1). Fish oil recipients had fewer cardiovascular events (P = 0.10); other clinical variables did not differ between the study groups. Low-density lipoprotein cholesterol levels tended to be greater in the fish oil group. Conclusion Dietary intake of omega-3 fatty acids modestly mitigates the course of coronary atherosclerosis in humans.
- Published
- 1999
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