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Tracey Weiss,1 Richard D Carr,2,3 Sampriti Pal,4 Lingfeng Yang,1 Baanie Sawhney,4 Robert Boggs,1 Swapnil Rajpathak,1 Kristy Iglay1 1Center for Observational and Real-World Evidence, Merck & Co., Inc, Kenilworth, NJ, 07033, USA; 2Global Medical Affairs, Merck Sharp & Dohme Limited (MSD), Hoddesdon, EN11 9BU, UK; 3Hatter Cardiovascular Institute, University College London, London, WC1E 6HX, UK; 4Real-World Evidence, Complete HEOR Solutions (CHEORS), Pennsylvania, PA, 19454, USACorrespondence: Tracey Weiss Tel +1 (908) 873-9697Email tracey.weiss@merck.comAim: To assess adherence and discontinuation of injectable glucagon-like peptide-1 receptor agonists (GLP-1 RA) at 12 and 24 months among adult type 2 diabetes mellitus (T2DM) patients in the United States initiating GLP-1 RA using the administrative claims-based database, Optum Clinformatics® Data Mart 7.1.Methods: A retrospective study was conducted from 01/2009 to 12/2017. Patients were required to be continuously enrolled for 12 months prior to their first GLP-1 RA prescription. Proportion of days covered (PDC) from prescription claims ≥ 0.80 defined adherence. Discontinuation was defined as a ≥ 90-day gap from the last date of GLP-1 RA supply to the first date of subsequent prescription claim.Results: A total of 4791 T2DM patients had ≥ 1 and 3907 had ≥ 2 GLP-1 RA prescription claims. 50.9% and 47.4% of patients were adherent at 12 and 24 months, respectively. Adherence was significantly higher among patients on weekly vs daily doses (p< 0.001). Median time to discontinuation was 13 months. The discontinuation rate was 47.7% and 70.1% at 12 and 24 months, respectively, with differences at 24 months for age and dosing frequency (p< 0.001 for both).Conclusion: Over half of T2DM patients initiating GLP-1 RA were non-adherent and the majority (70.1%) discontinued therapy by 24 months. Reasons for non-adherence and discontinuation merit further research.Keywords: GLP-1 RA, adherence, discontinuation, United States

Kaan Tunceli,1 Changgeng Zhao,1 Michael J Davies,2 Kimberly G Brodovicz,3 Charles M Alexander,4 Kristy Iglay,1 Larry Radican1 1Global Health Outcomes, Merck & Co, Inc, Whitehouse Station, NJ, USA; 2Global Scientific and Medical Publications, Merck & Co, Inc, Whitehouse Station, NJ, USA; 3Global Epidemiology, Merck & Co, Inc, Whitehouse Station, NJ, USA; 4Global Medical Affairs, Merck & Co, Inc, Whitehouse Station, NJ, USA Aim: To estimate the rate of adherence to oral antihyperglycemic monotherapy for patients with type 2 diabetes in the US and describe factors associated with adherence in these patients.Materials and methods: In this retrospective cohort analysis, patients aged 18 years or older with a type 2 diabetes diagnosis received between 1 January 2007 and 31 March 2010 were identified using a large US-based health care claims database. The index date was defined as the date of the first prescription for oral antihyperglycemic monotherapy during this period. Patients had to have continuous enrollment in the claims database for 12 months before and after the index date. Adherence was assessed using proportion of days covered (PDC) and an adjusted logistic regression analysis was performed to evaluate factors associated with adherence (PDC ≥80%).Results: Of the 133,449 eligible patients, the mean age was 61 years and 51% were men. Mean PDC was 75% and the proportion of patients adherent to oral antihyperglycemic monotherapy was 59%. Both mean PDC and PDC ≥80% increased with increasing age and the number of concomitant medications, and were slightly higher in men compared to women. Results from the logistic regression demonstrate an increased likelihood of non-adherence for patients who were younger, new to therapy, on a twice-daily dose, female, or on fewer than three concomitant medications compared to their reference groups. Higher average daily out-of-pocket pharmacy expense was also associated with an increased likelihood of non-adherence. All results were statistically significant (P

A Brett Hauber,1 Steven Han,2,3 Jui-Chen Yang,1 Ira Gantz,2 Kaan Tunceli,2 Juan Marcos Gonzalez,1 Kimberly Brodovicz,2 Charles M Alexander,2 Michael Davies,2 Kristy Iglay,2 Qiaoyi Zhang,2 Larry Radican2 1Health Preference Assessment, Research Triangle Institute (RTI) Health Solutions, Research Triangle Park, NC, USA; 2Merck Sharp and Dohme Corporation, Whitehouse Station, NJ, USA; 3Temple University, Philadelphia, PA, USA Purpose: To quantify willingness-to-pay (WTP) for reducing pill burden and dosing frequency among patients with type 2 diabetes mellitus (T2DM), and to examine the effect of dosing frequency and pill burden on likely medication adherence. Patients and methods: Participants were US adults with T2DM on oral antihyperglycemic therapy. Each patient completed an online discrete-choice experiment (DCE) with eight choice questions, each including a pair of hypothetical medication profiles. Each profile was defined by reduction in average glucose (AG), daily dosing, chance of mild-to-moderate stomach problems, frequency of hypoglycemia, weight change, incremental risk of congestive heart failure (CHF), and cost. Patients were asked to rate their likely adherence to the profiles presented in each question. Choice questions were based on a predetermined experimental design. Choice data were analyzed using random-parameters logit. Likely treatment adherence was analyzed using a Heckman two-stage model. Results: Of the 1,114 patients who completed the survey, 90 had lower dosing burden (

Abstract Objectives: To compare effects of fixed-dosed combinations (FDCs) and coadministered dual therapy (CDT) of antihyperglycemic agents on glycemic control (i.e., HbA(1c)) and medication adherence. Methods: A systematic literature review and meta-analysis were performed to compare the HbA(1c) response and medication adherence between the two drug regimens. Selected articles were limited to studies that compared equivalent drug components within FDC and CDT. Searches used PubMed, Embase, Web of Knowledge, and Cochrane databases. The search results were independently screened and reviewed by two authors (SH, KI). Of the 1246 identified abstracts, 152 articles were reviewed, and ten met the inclusion criteria. Results were extracted and pooled in a meta-analysis, using a random-effects model. Cohort comparisons were described as mean differences (MDs) with 95% confidence intervals (CIs). Results: The ten articles that met the inclusion criteria had a total study size of 70,573 patients. Four articles reported HbA(1c) results, which had a total of five cohort comparisons of FDC and CDT use. The meta-analysis revealed a significantly greater HbA(1c) reduction with FDC (MD = -0.53% [95% CI: -0.78, -0.28]; p < 0.0001). Eight studies evaluated medication adherence (measured as medication possession ratio [MPR]). Of the eight studies reporting MPR results, a total of 12 cohort comparisons were made and were further divided into three subgroups based on comparison types. Five comparisons described MPR for FDC versus CDT cohorts, with significantly higher MPR with FDC (MD = 8.6% [95% CI: 1.6, 15.6]; p = 0.0162]). Four comparisons examined patients who switched from monotherapy to FDC or CDT, with higher MPR for patients who switched to FDC (MD = 7.7% [95% CI: 5.7, 9.6]; p < 0.0001). Three comparisons described results for patients who switched from CDT to FDC or stayed on CDT, with higher MPR for patients who switched to FDC (MD = 5.0% [95% CI: 3.1, 6.8]; p < 0.0001). Limitations: A limited number of published studies were available for this meta-analysis and all of those included were observational studies. There was heterogeneity between studies in the statistical methods used to control for confounding variables and differing population characteristics. Conclusions: In a meta-analysis, use of FDCs with antihyperglycemic agents was associated with lower HbA(1c) and higher MPR values compared to CDT use in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

A systematic literature review was conducted to determine the incidence and mortality of QT-interval prolongation (QTp), torsades de pointes (TdP), and heart failure (HF) in patients with non-small cell lung cancer (NSCLC) who received epidermal growth factor receptor (EGFR) TKIs. Of 296 identified publications, 95 met eligibility criteria and were abstracted for QTp/TdP and HF outcomes (QTp/TdP: 83 publications, including 5 case study publications; HF: 79 publications, including 6 case study publications [involving 8 patients]). QTp incidence ranged from 0% to 27.8% in observational studies and from 0% to 11% in clinical trials, with no deaths due to QTp. There were no TdP events or deaths due to TdP. The incidence of HF ranged from 0% to 8%, and HF mortality rates ranged from 0% to 4%. Patients receiving treatment with EGFR TKIs should be monitored for signs of QTp, TdP, and HF per prescribing information. Standardized definitions and methods to improve monitoring of QTp, TdP, and HF-related events are needed in patients with NSCLC., Competing Interests: Disclosure B.K. is employed by Takeda. B.C. was employed by Takeda during the time this research was conducted. K.I. consulted on this project through CERobs Consulting, LLC; K.I. reports that Takeda Pharmaceuticals contracted with CERobs Consulting, LLC, a consulting firm with focus on real-world evidence, outcomes research, and epidemiology and clinical outcome assessments, including patient reported outcomes. K.R. consulted on this project through CERobs Consulting, LLC; K.R. reports that Takeda Pharmaceuticals contracted with CERobs Consulting, LLC, a consulting firm with focus on real-world evidence, outcomes research, and epidemiology and clinical outcome assessments, including patient reported outcomes. N.R-O. consulted on this project through CERobs Consulting, LLC; N.R-O. reports that Takeda Pharmaceuticals contracted with CERobs Consulting, LLC, a consulting firm with focus on real-world evidence, outcomes research, and epidemiology and clinical outcome assessments, including patient reported outcomes. W.S. is employed by Takeda. E.F. is employed by Takeda., (Copyright © 2024 Takeda Development Center Americas, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: This study was undertaken to evaluate the potential risk of acute pancreatitis with empagliflozin in patients with type 2 diabetes (T2D) newly initiating empagliflozin., Methods: Data from two large US claims databases were analyzed in an observational study of patients with T2D receiving metformin who were newly prescribed empagliflozin versus sulfonylurea (SU). Because dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists have been associated with the risk of acute pancreatitis in some studies, patients on these agents were excluded. Using pooled analyses of data from the two databases (2014-2021), patients initiating empagliflozin were matched 1:1 within database to patients initiating SU using propensity scores (PS) that incorporated relevant demographic and clinical characteristics. Prespecified sensitivity analyses were performed for design parameters., Results: The analyses identified 72 661 new users of empagliflozin and 422 018 new users of SUs, with both patient groups on concurrent metformin therapy. Baseline characteristics within treatment groups appeared to be similar across the 72 621 matched pairs. After mean follow-up of ~6 months, incidence rates of acute pancreatitis in the pooled matched cohort were 10.30 (95% confidence interval [CI] 9.29-11.39) events per 1000 patient-years (PY) for empagliflozin and 11.65 (95% CI 10.59-12.77) events per 1000 PY for SUs. On a background of metformin, patients newly initiating empagliflozin did not have an increased risk of acute pancreatitis compared with those initiating an SU (pooled PS matched hazard ratio 0.88 [0.76-1.02]) across 75621.42 PY of follow-up., Conclusions: The results of this voluntary post-approval safety study provide additional evidence that the use of empagliflozin for the treatment of T2D is not associated with an increased risk of acute pancreatitis., (© 2024 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Introduction: This systematic literature review (SLR) assessed incidence/prevalence of cryptoglandular fistulas (CCF) and outcomes associated with local surgical and intersphincteric ligation procedures for CCFs., Methods: Two trained reviewers searched PubMed and Embase for observational studies evaluating the incidence/prevalence of cryptoglandular fistula and clinical outcomes of treatments for CCF after local surgical and intersphincteric ligation procedures for CCF., Results: In total 148 studies met a priori eligibility criteria for all cryptoglandular fistulas and all intervention types. Of those, two assessed incidence/prevalence of cryptoglandular fistulas. Eighteen reported clinical outcomes of surgeries of interest in CCF and were published in the past 5 years. Prevalence was reported as 1.35/10,000 non-Crohn's patients, and 52.6% of non-IBD patients were found to progress from anorectal abscess to fistula over 12 months. Primary healing rates ranged from 57.1% to 100%; recurrence occurred in a range of 4.9-60.7% and failure in 2.8-18.0% of patients. Limited published evidence suggests postoperative fecal incontinence and long-term postoperative pain were rare. Several of the studies were limited by single-center design with small sample sizes and short follow-up durations., Discussion: This SLR summarizes outcomes from specific surgical procedures for the treatment of CCF. Healing rates vary according to procedure and clinical factors. Differences in study design, outcome definition, and length of follow-up prevent direct comparison. Overall, published studies offer a wide range of findings with respect to recurrence. Postsurgical incontinence and long-term postoperative pain were rare in the included studies, but more research is needed to confirm rates of these conditions following CCF treatments., Conclusion: Published studies on the epidemiology of CCF are rare and limited. Outcomes of local surgical and intersphincteric ligation procedures show differing success and failure rates, and more research is needed to compare outcomes across various procedures. (PROSPERO; registration number CRD42020177732)., (© 2023. The Author(s).)

Introduction: Hereditary factor XI (FXI) deficiency is a rare coagulation disorder that may result in excessive bleeding requiring intervention to restore haemostasis., Aim: The aim of this review was to report the current knowledge of the worldwide incidence and prevalence of FXI deficiency., Methods: A targeted PubMed search using terms related to FXI deficiency was conducted to identify studies published from April 2002 through April 2022. A manual search supplemented the electronic search. Studies were eligible for data abstraction if they reported population-based incidence proportions/rates or prevalence proportions for FXI deficiency., Results: The electronic and manual searches returned 253 publications. After applying exclusion criteria, seven publications were included in the analysis, including a global report from the World Federation of Haemophilia (WFH). Six publications provided information on the prevalence of FXI deficiency that included 74 countries and regions. The estimated prevalence of FXI in the WFH report ranged from 0/100,000 in several countries to 55.85/100,000 individuals in the United Kingdom. Prevalence estimates in the PubMed findings ranged from .1 to 246.2/1,000,000 inhabitants with varying methods of case identification and time periods of analysis. One study estimated the incidence of FXI deficiency in Yecla, Spain at 2% of blood donors and .09% of hospital inpatients/outpatients with activated partial thromboplastin time (aPTT) tests., Conclusion: FXI deficiency is rare across the world, but additional steps could be taken to improve incidence and prevalence estimation, for example, development of a consistent FXI deficiency definition and incorporating genetic testing into a clinical routine to better identify and characterise cases., (© 2022 The Authors. Haemophilia published by John Wiley & Sons Ltd.)

Background: Enterocutaneous fistulas (ECF) are rare sequelae of Crohn's disease (CD) that occur either postoperatively or spontaneously. ECFs are associated with high morbidity and mortality. This systematic literature review assesses the disease burden of CD-related ECF and identifies knowledge gaps around incidence/prevalence, treatment patterns, clinical outcomes, healthcare resource utilization (HCRU), and patient-reported outcomes (PROs)., Methods: English language articles published in PubMed and Embase in the past 10 years that provided data and insight into the disease burden of CD-related ECF (PROSPERO Registration number: CRD42020177732) were identified. Prespecified search and eligibility criteria guided the identification of studies by two reviewers who also assessed risk of bias., Results: In total, 582 records were identified; 316 full-text articles were assessed. Of those, eight studies met a priori eligibility criteria and underwent synthesis for this review. Limited epidemiologic data estimated a prevalence of 3265 persons with ECF in the USA in 2017. Clinical response to interventions varied, with closure of ECF achieved in 10% to 62.5% of patients and recurrence reported in 0% to 50% of patients. Very little information on HCRU is available, and no studies of PROs in this specific population were identified., Conclusion: The frequency, natural history, and outcomes of ECF are poorly described in the literature. The limited number of studies included in this review suggest a high treatment burden and risk of substantial complications. More robust, population-based research is needed to better understand the epidemiology, natural history, and overall disease burden of this rare and debilitating complication of CD., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Proton-pump inhibitors (PPIs) are widely prescribed as acid-suppression therapy. Some observational studies suggest that long-term use of PPIs is potentially associated with certain adverse kidney outcomes. We conducted a systematic literature review to assess potential bias in non-randomized studies reporting on putative associations between PPIs and adverse kidney outcomes (acute kidney injury, acute interstitial nephritis, chronic interstitial nephritis, acute tubular necrosis, chronic kidney disease, and end-stage renal disease)., Methods: We searched the medical literature within 10 years of 17 December 2020. Pre-specified criteria guided identification of relevant English language articles for assessment. Risk of bias on an outcome-specific basis was evaluated using the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool by two independent reviewers., Results: Of 620 initially identified records, 26 studies met a priori eligibility criteria and underwent risk of bias assessment. Nineteen studies were judged as having a moderate risk of bias for reported adverse kidney outcomes, while six studies were judged as having a serious risk of bias (mainly due to inadequate control of confounders and selection bias). We were unable to determine the overall risk of bias in two studies (one of which was assessed as having a moderate risk of bias for a different adverse kidney outcome) due to insufficient information presented. Effect estimates for PPIs in relation to adverse kidney outcomes varied widely (0.24-7.34) but associations mostly showed increased risk., Conclusion: Using ROBINS-I, we found that non-randomized observational studies suggesting kidney harm by PPIs have moderate to serious risk of bias, making it challenging to establish causality. Additional high-quality, real-world evidence among generalizable populations are needed to better understand the relation between PPI treatment and acute and chronic kidney outcomes, accounting for the effects of varying durations of PPI treatment, self-treatment with over-the-counter PPIs, and potential critical confounders., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Takeda Pharmaceuticals contracted with CERobs Consulting, LLC, a consulting firm with focus on real-world evidence observational research, comparative effectiveness research, pragmatic randomized trials, outcomes research, epidemiology, and clinical outcome assessments, including patient-reported outcomes. PR, KI, TR, and CJG consulted on this project through CERobs Consulting, LLC. KK-Z has received honoraria and/or support from Abbott, Abbvie, ACI Clinical (Cara Therapeutics), Akebia, Alexion, Amgen, Ardelyx, ASN (American Society of Nephrology), Astra-Zeneca, Aveo, BBraun, Chugai, Cytokinetics, Daiichi, DaVita, Fresenius, Genentech, Haymarket Media, Hofstra Medical School, IFKF (International Federation of Kidney Foundations), ISH (International Society of Hemodialysis), International Society of Renal Nutrition & Metabolism (ISRNM), JSDT (Japanese Society of Dialysis Therapy), Hospira, Kabi, Keryx, Kissei, Novartis, OPKO, NIH (National Institutes of Health), NKF (National Kidney Foundations), Pfizer, Regulus, Relypsa, Resverlogix, Dr Schaer, Sandoz, Sanofi, Shire, VA (Veterans’ Affairs), Takeda, Vifor, UpToDate, ZS-Pharma. DB is a salaried employee of Takeda Pharmaceuticals., (© The Author(s), 2022.)

Background: Crohn's disease (CD)-related rectovaginal fistulas (RVFs) and anovaginal fistulas (AVFs) are rare, debilitating conditions that present a substantial disease and treatment burden for women. This systematic literature review (SLR) assessed the burden of Crohn's-related RVF and AVF, summarizing evidence from observational studies and highlighting knowledge gaps., Methods: This SLR identified articles in PubMed and Embase that provide data and insight into the patient experience and disease burden of Crohn's-related RVF and AVF. Two trained reviewers used pre-specified eligibility criteria to identify studies for inclusion and evaluate risk of bias using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool for observational studies., Results: Of the 582 records identified, 316 full-text articles were assessed, and 16 studies met a priori eligibility criteria and were included. Few epidemiology studies were identified, with one study estimating the prevalence of RVF to be 2.3% in females with Crohn's disease. Seven of 12 treatment pattern studies reported that patients had or required additional procedures before and/or after the intervention of interest, demonstrating a substantial treatment burden. Seven of 11 studies assessing clinical outcomes reported fistula healing rates between 50 and 75%, with varying estimates based on population and intervention., Conclusions: This SLR reports the high disease and treatment burden of Crohn's-related RVF and AVF and identifies multiple evidence gaps in this field. The literature lacks robust, generalizable data, and demonstrates a compelling need for substantial, novel research into these rare and debilitating sequelae of CD. Registration The PROSPERO registration number for the protocol for this systematic literature review is CRD42020177732., (© 2022. The Author(s).)

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a type 2 diabetes mellitus (T2DM) treatment with demonstrated weight loss benefits in clinical trials. However, the extent to which real-world patients with T2DM achieve clinically meaningful weight loss (≥5%) has not been well characterized. Analysis of real-world data suggests adherence to injectable GLP-1 RAs is suboptimal and discontinuation following the first year of therapy is poorly characterized., Research Design and Methods: A retrospective cohort study among patients with T2DM initiating injectable GLP-1 RA therapy was conducted using the Clinical Practice Research Datalink that includes primary care medical records for 13 million patients in the UK. This study assessed weight change, adherence (proportion of days covered (PDC) ≥80%), and discontinuation (≥90-day gap between prescriptions) at 12 and 24 months during the study period spanning January 2009-December 2017., Results: Among 589 patients initiating a GLP-1 RA, 56.4% were female and the median age was 54 years (IQR (46, 61)). The median body mass index was 41.2 kg/m 2 (IQR (35.8, 46.4)). Among patients with weight measures available (n=341 at 12 months; n=232 at 24 months), 33.4% and 43.5% achieved weight loss ≥5% of baseline weight at 12 and 24 months, respectively. At 12 and 24 months, 64.5% and 59.2% were adherent, and 45.2% and 64.7% discontinued, respectively., Conclusions: A minority of patients initiating GLP-1 RAs achieved ≥5% weight loss, suggesting the real-world benefit of these agents on weight loss may be lower than that observed in clinical trials. Patients on GLP-1 RAs may benefit from additional support to improve long-term adherence., Competing Interests: Competing interests: TW, LY, RB, SR, and KI are/were employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey, USA at the time of study conduct. RDC was an employee of MSD UK, London, UK at the time of study conduct and holds an honorary position at University College, London, UK. BS and SP were external contractors of Complete HEOR Solutions whose analysis services were paid for by Merck & Co., Inc., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To investigate the prevalence of comorbid conditions/complications among Japanese patients with type 2 diabetes mellitus (T2DM) in a real-world setting., Methods: We performed retrospective analyses of a large-scale database directly linked to electronic medical records, J-DREAMS (Japan Diabetes compREhensive database project based on an Advanced electronic Medical record System), to determine the prevalence of clinically significant comorbid conditions/complications among Japanese patients with T2DM aged ≥ 20 years with ≥ 1 clinical encounter at a referral center between April 1, 2017 and March 31, 2019., Results: Data were available for 10,151 patients (39.2% female). The mean age and T2DM duration were 66.0 years and 16.1 years, respectively. Only 0.5% had isolated T2DM, 6.6% had one comorbid condition/complication, and the remainder had multiple comorbid conditions/complications. Dyslipidemia (84.7%) and hypertension (75.1%) were the most common, followed by chronic kidney disease (35.4%), retinopathy (23.1%), and cardiovascular diseases (22.1%). Overall, 36.0% of patients were overweight/obese (body mass index ≥ 25 kg/m 2 ) and 18.6% had a history of neoplasms. The prevalence of comorbid conditions/complications tended to increase with advancing age and duration of T2DM., Conclusions: We revealed a high prevalence of comorbid conditions/complications, including chronic kidney and cardiovascular diseases, in Japanese patients with T2DM., (Copyright © 2021 Merck Sharp & Dohme Corp., The Author(s). Published by Elsevier B.V. All rights reserved.)

Aims: The current study evaluated patient demographics and clinical characteristics that associated with HbA1c reduction following addition of one oral antidiabetic drug (OAD) to DPP4i monotherapy., Methods: A retrospective study was conducted using CoDiC database. Adult T2DM patients treated with sitagliptin monotherapy for ≥ 6 months and adding one OAD were extracted. Association between patient characteristics at the time of add-on OAD and following HbA1c reduction was assessed., Results: Of 444 included patients, mean age was 62 years and 33% were female. All add-on OAD classes demonstrated further HbA1c reduction ( p  < 0.05). The majority received biguanide (BG; 61%) or sulfonylurea (SU; 25%) add-on therapy. BG and SU groups showed a significant association between higher baseline HbA1c categories and greater HbA1c reductions (BG: - 0.24 to - 1.75%, p  < 0.0001; SU: - 0.15 to - 2.11%, p  < 0.0001). Lower HDL-cholesterol/higher non-HDL-cholesterol (BG), male gender (SU), and lower SBP (SU) were associated with larger HbA1c reductions. The results for baseline HbA1c (BG and SU) and gender (SU) were also confirmed by multivariate analysis., Conclusion: The majority of Japanese T2DM patients on sitagliptin monotherapy who require an add-on OAD utilized BG or SU. There were 2 determinants of glycemic response: baseline HbA1c with BG and SU and gender with SU during add-on OAD therapy., Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-021-00514-5., Competing Interests: Conflict of interestKoichi Kawai., Azuma Kanatsuka., Shinobu Motohashi, and Katsuya Yamazaki have no potential conflicts of interest to declare. Hiroshi Maegawa has received lecture fees from MSD K.K., Nippon Boehringer Ingelheim Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Sanofi K.K., Astellas Pharma Inc., Takeda Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Novo Nordisk Pharma Ltd., Eli Lilly Japan K.K. Sumitomo Dainippon Pharma Co. Ltd., and Astra Zeneca K.K.; research supports from Astellas Pharma Inc., Astra Zeneca K.K., Nippon Boehringer Ingelheim Co. Ltd., Sunstar Inc., Mitsubishi Tanabe Pharma Corporation, Kyowa Hakko Kirin Co. Ltd., Nissan Chemical Corporation and MIKI Corporation; grants from Takeda Pharmaceutical Co. Ltd., Astellas Pharma Inc., MSD K.K., Nippon Boehringer Ingelheim Co. Ltd., Kyowa Hakko Kirin Co. Ltd., Taisho Pharma Co. Ltd., Kowa Pharmaceutical Co. Ltd., Ono Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Sanofi K.K., Mitsubishi Tanabe Pharma Corporation, Sanwa Kagaku Kenkyusho Co. Ltd., Eli Lilly Japan K.K., Sumitomo Dainippon Pharma Co. Ltd., Novo Nordisk Pharma Ltd., Bayer Yakuhin Ltd., Teijin Pharma Limited, Shionogi & Co. Ltd.,, Novartis Pharma K.K. and Nipro Corporation. Jun-ichi Eiki, Akira Wakana, Ai Hayashi, Kristy Iglay and Shigeru Tokita are current or former employees of MSD K.K., Tokyo, Japan or Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and may own stock and/or hold stock options in Merck & Co., Inc., Kenilworth, NJ, USA., (© The Japan Diabetes Society 2021, corrected publication 2021.)

Introduction: To assess secondary metformin monotherapy (MM) failure in a real-world type 2 diabetes mellitus (T2DM) cohort., Research Design and Methods: Using the IQVIA Electronic Medical Record (formerly GE Centricity) database, adults with T2DM who initiated MM between January 1, 2012 and June 30, 2016 and achieved glycemic control (hemoglobin A1c (HbA1c) <7% (53 mmol/mol); index date) were analyzed. Secondary MM failure was defined in two ways: loss of glycemic control (HbA1c ≥7% (53 mmol/mol)) and treatment change (addition or switch of antihyperglycemic agent). Multivariable logistic regression models assessed the association between secondary MM failure and sociodemographic and clinical factors., Results: The analysis included 4775 patients initiating MM. 32.9% and 19.2% experienced secondary MM failure at 24 months measured as loss of glycemic control and treatment change, respectively. Multivariable logistic regression found that women (OR=1.3, 95% CI 1.1 to 1.5) compared with men, lower Charlson Comorbidity Index (CCI) (OR=0.89, 95% CI 0.86 to 0.93), and lower baseline HbA1c (OR=0.93, 95% CI 0.88 to 0.98) were associated with increased likelihood of loss of glycemic control. Lower CCI was associated with increased likelihood of treatment change (OR=0.78, 95% CI 0.75 to 0.82)., Conclusions: The observed frequency of secondary MM failure underscores the importance of the American Diabetes Association's recommendation for glycemic monitoring of at least every 6 months so that timely therapeutic adjustments can be made., Competing Interests: Competing interests: TW, LY, and SR are employees of Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey, USA. KI was an employee of Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc. at the time of study completion. LB is an employee of Ochsner Medical Center. TG was an employee of Complete HEOR Solutions, North Wales, Pennsylvania, USA, which was contracted to complete the study analysis on behalf of Merck & Co., Inc., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The objective of this study was to describe the pattern of comorbidities in patients with type 2 diabetes mellitus with and without atherosclerotic cardiovascular disease. Methods: This was a retrospective, cross-sectional analysis of the IQVIA Commercial Data Delivery database. Patients were ≥18 years on their last encounter between 1 October 2014 and 30 September 2015 and had either a type 2 diabetes mellitus diagnosis or a prescription for an oral diabetes medication. Atherosclerotic cardiovascular disease was confirmed by diagnosis codes. Comorbidities were identified using diagnosis codes, clinical measurements, and/or medication use. Results: A total of 1,522,526 type 2 diabetes mellitus patients were included in the analysis, 25% of whom had atherosclerotic cardiovascular disease. The most common comorbidities were hypertension, hyperlipidemia, overweight/obesity, chronic kidney disease, congestive heart failure, and neuropathy. These were present, respectively, in the following percentages of patients with and without cardiovascular disease: 98.3 and 91.0%, 94.8 and 78.5%, 80.5 and 80.6%, 38.5 and 18.9, 20.2, and 4.3%, and 13.7 and 8.6%. Thus, the frequencies of hyperlipidemia, chronic kidney disease, and congestive heart failure were notably higher in patients with cardiovascular disease. This trend held true for patients grouped by sex, age, and race. Conclusions: Patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease have different rates of certain comorbidities compared to those without atherosclerotic cardiovascular disease.

Background/rationale: Long-term treatment with anticholinergic agents may increase the risk of cognitive impairment or dementia. This systematic literature review and meta-analysis aimed to assess the impact of ≥3 months of exposure to anticholinergics as a class on the risk of dementia, mild cognitive impairment, and change in cognitive function. The impact of anticholinergic agents specifically used to treat overactive bladder was also evaluated., Materials and Methods: A systematic literature review was conducted to identify English language articles evaluating the impact of anticholinergic use for ≥3 months on dementia or cognitive function in adult patients. Databases searched included PubMed, Embase, and the Cochrane Library. Meta-analyses were conducted using random-effects models; 95% confidence intervals (CIs) and 95% prediction intervals (PIs) were reported., Results: A total of 2122 records were identified. Out of those, 21 studies underwent qualitative synthesis and 6 reported endpoints relevant for inclusion in a meta-analysis assessing the risk of incident dementia. The overall rate ratio for incident dementia was 1.46 (95% CI: 1.17-1.81; 95% PI: 0.70-3.04; n = 6). The risk of incident dementia increased with increasing exposure (n = 3). In addition, two studies from the meta-analysis reported an increased risk of dementia with ≥3 months of use of bladder antimuscarinics (adjusted odds ratios ranged from 1.21 to 1.65, depending on exposure category)., Conclusion: Anticholinergic use for ≥3 months increased the risk of dementia on average by an estimated 46% versus nonuse. This relationship was consistent in studies assessing overactive bladder medications. The risk of developing dementia should be carefully considered in the context of potential benefit before prescribing anticholinergics., (© 2020 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Introduction: To investigate factors affecting glycemic control, oral antidiabetic drug (OAD) treatment distribution and self-care activities among patients with type 2 diabetes mellitus (T2DM) who newly initiate OAD monotherapy in a real-world setting in Japan., Research Design and Methods: A Real-world Observational Study on Patient Outcomes in Diabetes (RESPOND) is an ongoing, prospective, observational cohort study with follow-up at 6, 12, 18 and 24 months. Primary objectives include OAD treatment patterns (cross-sectional and longitudinal) among diabetes specialists versus non-specialists; adherence to diabetes self-care activities; quality of life; treatment satisfaction among patients and target attainment rates of parameters, including glycated hemoglobin. Here, we present the study design and baseline data., Results: Of 1506 patients enrolled (June 2016-May 2017; 174 sites in Japan), 1485 were included in the baseline analysis (617 treated by specialists, 868 by non-specialists). Most patients were prescribed dipeptidyl peptidase-4 inhibitors (DPP-4Is) (specialist vs non-specialist, 54.1% vs 57.1%), then sodium-glucose cotransporter 2 inhibitors (13.9% vs 22.2%), metformin (20.3% vs 12.9%) and other OADs (<5% individually in both groups). Regardless of age, body mass index and glycated hemoglobin, DPP-4Is were the most commonly prescribed OADs by both specialists and non-specialists. About one-fifth and one-third of patients visiting specialists and non-specialists, respectively, received no advice on diet and exercise. The proportion of patients following self-care recommendations for diet and exercise (2/5 items on the Summary of Diabetes Self-Care Activities) was significantly higher among those visiting specialists than non-specialists., Conclusion: The use of newer OAD was common across a broad range of clinical characteristics in patients with T2DM who newly initiated monotherapy in Japan. However, patient-related and physician-related factors could affect the treatment changes during the following course of treatment. In addition, treatment outcome could vary with the observed difference in the level of patient education provided by diabetes specialists versus non-specialists., Competing Interests: Competing interests: DY has received personal fees from MSD during the conduct of the study. His relevant financial activities outside the submitted work are grants and personal fees from Nippon Boehringer Ingelheim and Novo Nordisk and grants from Ono, Taisho Toyama, Takeda, Terumo and Arkray. HH has received personal fees and non-financial support from MSD during the conduct of the study and grants from Novartis outside the submitted work. TK has received consulting fees from MSD for the work under consideration for publication. His relevant financial activities outside the submitted work are contract research funds from AstraZeneca and Takeda; joint research funds from Daiichi Sankyo; grants from Astellas, Daiichi Sankyo, Eli Lilly, Kissei, Mitsubishi Tanabe, MSD, Novo Nordisk, Ono, Sanofi, Sumitomo Dainippon, Taisho and Takeda and fees for consulting and/or lectures from Abbott, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Cosmic, Daiichi Sankyo, Eli Lilly, Fujifilm, Johnson & Johnson, Kissei, Kowa, Kyowa Hakko Kirin, Medical Review, Medical View, Medscape Education, Medtronic Sofamor Danek, Mitsubishi Tanabe, MSD, Musashino Foods, Nipro, Novartis, Novo Nordisk, Ono, Sanofi, Sanwa Kagaku, Sumitomo Dainippon, Taisho, Takeda and Terumo. He has also been an Endowed Chair for Asahi Mutual Life Insurance, Boehringer Ingelheim, Kowa, Mitsubishi Tanabe, MSD, Novo Nordisk, Ono and Takeda. HO has received personal fees from MSD during the conduct of the study. IS has received grants and personal fees from MSD during the conduct of the study. His relevant financial activities outside the submitted work are grants and personal fees from Astellas, AstraZeneca, Mitsubishi Tanabe, Eli Lilly, Novo Nordisk, Ono, Sanofi and Takeda; grants from Daiichi Sankyo, Kissei, Kowa, Kyowa Hakko Kirin, Mochida, Novartis, Rohto, Shionogi, Sumitomo Dainippon, Teijin and Terumo and personal fees from Kowa, Nippon Boehringer Ingelheim and Sanwa Kagaku. HW has received grants and personal fees from MSD during the conduct of the study. His relevant financial activities outside the submitted work are grants and personal fees from Astellas, Daiichi Sankyo, Eli Lilly, Mitsubishi Tanabe, Nippon Boehringer Ingelheim, Novartis, Novo Nordisk, Ono, Sanofi, Sanwa Kagaku, Sumitomo Dainippon and Takeda; grants from Johnson & Johnson, Teijin, Yakult, Kissei, Kowa, Kyowa Hakko Kirin, Pfizer and Taisho Toyama and personal fees from Fujifilm, Terumo and AstraZeneca. KI was employed by Merck & Co., Inc., Kenilworth, New Jersey, USA, during the conduct of this study and owns stock. YS has received personal fees from MSD during the conduct of the study. His relevant financial activities outside the submitted work are grants and personal fees from Novo Nordisk and Taisho Toyama; grants from Arkray Marketing, Bayer, Boehringer Ingelheim, Ono, Sumitomo Dainippon and Terumo and personal fees from Kao, Nippon Becton Dickinson, Nippon Boehringer Ingelheim, Taisho and Takeda. KT and ST are employees of MSD K.K. and own stock., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess the level of glycemic control among type 2 diabetes patients on sodium-glucose cotransporter 2 inhibitor (SGLT2i) and metformin dual therapy., Methods: Observational, retrospective database study in adult type 2 diabetes mellitus patients from the IQVIA Electronic Medical Record (EMR) database was conducted. The observation period was June 2015 to June 2018. Patient's earliest encounter in the observation period while on SGLT2i and metformin dual therapy served as the index date. Patients were required to have at least one HbA1c measure in the 12 months prior to the index date and be on SGLT2i and metformin dual therapy and no other antihyperglycemic treatment as of the HbA1c measurement date or any time during the 90 days prior. The associations between sociodemographic factors and clinical burden on achievement of HbA1c <8% were assessed using multivariable logistic regression with backward stepwise selection., Results: Of 3491 patients, 2176 (62.3%) achieved HbA1c <8%, with a median distance to goal of 1.1% (IQR 0.5-2.3%) for those not at glycemic target. Mean age was 56.5 years and 52.6% were male. At baseline, 28.3% of patients had established cardiovascular disease/chronic kidney disease, and of those 63.8% had HbA1c <8%. African American patients had lower odds of attaining HbA1c <8% when compared with white patients [OR 0.69], while older patients had marginally higher odds [OR 1.01]., Conclusion: Approximately 3 out of 5 patients on metformin and SGLT2i dual therapy achieved HbA1c <8%, with African Americans having a lower likelihood of achieving this glycemic goal.

Background: A substantial proportion of patients with type 2 diabetes mellitus (T2DM) do not reach their target HbA1c level on metformin. The objective of this retrospective observational cohort study is to better characterize the distance between HbA1c target and patient's actual HbA1c level (the distance to goal), using a target HbA1c of 7.0% (53 mmol/mol), in patients with T2DM who have started metformin monotherapy. Methods: We used data from the GE Centricity Electronic Medical Record database by IQVIA in 2016 in the United States (US) to identify adults with T2DM who started metformin monotherapy (MM) and received at least 90 days of treatment. Patients were categorized into three groups: those who achieved the goal of HbA1c <7.0%, those who did not achieve the goal of HbA1c <7.0% (i.e. failed MM) and received intensified treatment, and those who failed MM and did not receive intensified treatment. Distance to goal was computed for patients in each group. Results: We identified 20,704 patients in the US database who started MM; 1741 (8.4%) failed MM and received intensified treatment, while 4977 (24.0%) failed MM and did not receive intensified treatment. The mean post-MM HbA1c for those who failed MM and received intensified treatment was 8.7% (72 mmol/mol) (median 8.2%, 66 mmol/mol) and the mean distance to goal was 1.7% (median 1.2%). The mean post-MM HbA1c for those who failed MM and did not receive intensified treatment was 8.0% (64 mmol/mol) (median 7.5%, 58 mmol/mol) and the mean distance to goal was 1.0% (median 0.5%). Conclusion: A proportion of US T2DM patients do not achieve glycemic control (target HbA1c < 7.0%) despite 90 days of MM. Patients who failed MM and eventually received intensified treatment did so when their HbA1c distance to goal exceeded the level at which one add-on therapy alone might be sufficient to bring them to goal.

Objective: Hypoglycemia (HG) occurs in up to 60% of patients with diabetes mellitus (DM) each year. We assessed a HG alert tool in an electronic health record system, and determined its effect on clinical practice and outcomes. Methods: The tool applied a statistical model, yielding patient-specific information about HG risk. We randomized outpatient primary-care providers (PCPs) to see or not see the alerts. Patients were assigned to study group according to the first PCP seen during four months. We assessed prescriptions, testing, and HG. Variables were compared by multinomial, logistic, or linear model. ClinicalTrials.gov ID: NCT04177147 (registered on 22 November 2019). Results: Patients ( N = 3350) visited 123 intervention PCPs; 3395 patients visited 220 control PCPs. Intervention PCPs were shown 18,645 alerts (mean of 152 per PCP). Patients' mean age was 55 years, with 61% female, 49% black, and 49% Medicaid recipients. Mean baseline A1c and body mass index were similar between groups. During follow-up, the number of A1c and glucose tests, and number of new, refilled, changed, or discontinued insulin prescriptions, were highest for patients with highest risk. Per 100 patients on average, the intervention group had fewer sulfonylurea refills (6 vs. 8; p < .05) and outpatient encounters (470 vs. 502; p < .05), though the change in encounters was not significant. Frequency of HG events was unchanged. Conclusions: Informing PCPs about risk of HG led to fewer sulfonylurea refills and visits. Longer-term studies are needed to assess potential for long-term benefits.

Objective: Type 2 diabetes (T2D) is a prevalent health problem. Oral agents, with the exception of metformin, are often discontinued with the initiation of insulin. The objective was to understand the proportion of patients discontinuing dipeptidyl peptidase-4 inhibitors (DPP-4is) and the reasons for the decision to discontinue. Methods: A retrospective study using a health claims database investigated discontinuation of DPP-4i in adult patients on a dual therapy of metformin and DPP-4i who initiated insulin ( n  = 3391). An online survey administered to 406 physicians in the US examined reasons for discontinuation. Physicians surveyed included endocrinologists (34.5%), general practitioners (32.5%), internal medicine specialists (30.5%), and diabetologists (2.5%), treating a monthly average of 154 patients. Results: Among patients treated with metformin and DPP-4is who were newly prescribed insulin, 33.3 and 57.3% discontinued DPP-4i therapy within 3 and 12 months, respectively. Patients who discontinued DPP-4i therapy had higher out-of-pocket costs and a greater proportion of renal and liver disease. Top 3 responses for discontinuation included adverse events/tolerability issues (58.9%), lack of efficacy/treatment goals not being met (55.4%) and additional cost of DPP-4i with insulin (48.5%). Top 3 responses for continuing DPP-4i included meeting treatment goals (70.7%), using a lower dose of insulin (65.3%) and good tolerability (48.0%). Physician characteristics, such as physician specialty, age, gender and location impacted to some extent the reasons for treatment decisions. Conclusions: A large proportion of patients discontinue DPP-4is in the real world when initiating insulin. The impact of physician characteristics in treatment decisions highlights the need for enhanced physician training and support as new clinical data emerges and therapy options are available.

Objectives: To determine if there is a difference in the outcomes of diabetes patients managed with high, intermediate, or low conformance to diabetes guidelines., Study Design: Retrospective database analysis., Methods: This was a retrospective database analysis of adults diagnosed with type 2 diabetes and with glycated hemoglobin (HbA1c) ≥7% (53 mmol/mol) who were commercially insured by, or receiving Medicare benefits through, Aetna. Subjects were classified as having high, intermediate, or low conformance to current guidelines. Six, 12, and 18 months later, health care resource utilization, clinical outcomes, and costs were assessed using multivariable regression analysis to determine whether differences existed between patients with high, intermediate, and low conformance. Regression models were adjusted using pre-index variables, and the results were expressed as incidence rate ratios (IRRs) with 95% confidence intervals (CIs)., Results: A total of 21,171 individuals were included in the analysis. In analyses of patients with low versus high conformance, pharmacy costs were significantly lower over 18 months of outcome assessment (P < 0.001), but diabetes-related outpatient costs were significantly higher (P < 0.001). In analyses of patients with intermediate versus high conformance, diabetes-related outpatient costs were significantly greater at 12 and 18 months (P < 0.001 for both)., Conclusions: Reduced conformance to guidelines leads to higher diabetes-related costs., Competing Interests: At the time of the study, Rajesh R. Mehta, Alison M. Edwards, Ajay Sharma, and Kenneth J. Snow were employees of Healthagen Outcomes. At the time of the study, Swapnil Rajpathak and Kristy Iglay were employees and stockholders of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA., (© 2020 Published by Elsevier Inc.)

Aims: To assess the dose distribution among users of metformin monotherapy as well as the patterns of up-titration following initiation of therapy in people with type 2 diabetes mellitus (T2DM)., Materials and Methods: This was a retrospective cohort study of adults with T2DM in the United Kingdom (UK). Metformin dose distribution was assessed at 0, 6 and 12 months in people initiating metformin monotherapy (new users) and cross-sectionally in people with ongoing metformin monotherapy (prevalent users). Patterns and predictors of up-titration were also analysed in new users. Dose distributions and treatment patterns were assessed descriptively; predictors of up-titration were determined using multivariable logistic regressions., Results: Totals of 6174 new users and 8733 prevalent users were included. New users initiated metformin at >0 mg to ≤500 mg (25%), >500 mg to ≤1000 mg (47%), >1000 mg to ≤1500 mg (17%) or >1500 mg to ≤2000 mg (12%) daily. This distribution did not vary over time. Prevalent users of metformin received doses of >0 mg to ≤500 mg (14%), >500 mg to ≤1000 mg (40%), >1000 mg to ≤1500 mg (15%), >1500 mg to ≤2000 mg (29%) or >2000 mg (1%) daily. Among new users of metformin, 6.7% and 10.8% had been up-titrated at 6 and 12 months, respectively, despite the majority having glycated haemoglobin >53 mmol/mol. Predictors of up-titration included younger age and higher HbA1c., Conclusions: A majority of T2DM patients taking metformin received a dose ≤1000 mg/day. Up-titration of metformin is infrequent in the first year postinitiation., Competing Interests: Authors GF, MC and SR are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc, Kenilworth, NJ, USA. Author KI was an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc, Kenilworth, NJ, USA at the time of the analysis. Authors AF and KK received honoraria from Merck & Co., Inc for participation in the study. Author BS was an external contractor whose analysis services were paid for by Merck & Co., Inc, (© 2019 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Aims: To assess demographic and clinical characteristics associated with clinical inertia in a real-world cohort of type 2 diabetes mellitus patients not at hemoglobin A1c goal (<7%) on metformin monotherapy. Methods: Adult (≥18 years) type 2 diabetes mellitus patients who received care at Massachusetts General Hospital/Brigham and Women's Hospital and received a new metformin prescription between 1992 and 2010 were included in the analysis. Clinical inertia was defined as two consecutive hemoglobin A1c measures ≥7% ≥3 months apart while remaining on metformin monotherapy (i.e. without add-on therapy). The association between clinical inertia and demographic and clinical characteristics was examined via logistic regression. Results: Of 2848 eligible patients, 43% did not achieve a hemoglobin A1c goal of <7% 3 months after metformin monotherapy initiation. A sub-group of 1533 patients was included in the clinical inertia analysis, of which 36% experienced clinical inertia. Asian race was associated with an increased likelihood of clinical inertia (OR = 2.43; 95% CI = 1.48-3.96), while congestive heart failure had a decreased likelihood (OR = 0.58; 95% CI = 0.32-0.98). Chronic kidney disease and cardiovascular/cerebrovascular disease had weaker associations but were directionally similar to congestive heart failure. Conclusions: Asian patients were at an increased risk of clinical inertia, whereas patients with comorbidities appeared to have their treatment more appropriately intensified. A better understanding of these factors may inform efforts to decrease the likelihood for clinical inertia.

Objective: Hypoglycemia occurs in 20-60% of patients with diabetes mellitus. Identifying at-risk patients can facilitate interventions to lower risk. We sought to develop a hypoglycemia prediction model. Methods: In this retrospective cohort study, urban adults prescribed a diabetes drug between 2004 and 2013 were identified. Demographic and clinical data were extracted from an electronic medical record (EMR). Laboratory tests, diagnostic codes and natural language processing (NLP) identified hypoglycemia. We compared multiple logistic regression, classification and regression trees (CART), and random forest. Models were evaluated on an independent test set or through cross-validation. Results: The 38,780 patients had mean age 57 years; 56% were female, 40% African-American and 39% uninsured. Hypoglycemia occurred in 8128 (539 identified only by NLP). In logistic regression, factors positively associated with hypoglycemia included infection, non-long-acting insulin, dementia and recent hypoglycemia. Negatively associated factors included long-acting insulin plus sulfonylurea, and age 75 or older. The models' area under curve was similar (logistic regression, 89%; CART, 88%; random forest, 90%, with ten-fold cross-validation). Conclusions: NLP improved identification of hypoglycemia. Non-long-acting insulin was an important risk factor. Decreased risk with age may reflect treatment or diminished awareness of hypoglycemia. More complex models did not improve prediction.

Background: Sulfonylureas (SUs) can help manage type 2 diabetes mellitus, but often have side effects. The objective of this study was to identify factors impacting physicians' decisions to discontinue (DC) or down-titrate (DT) SU therapy., Methods: 1,026 physicians from the All Global panel were asked to rate level of concern regarding potential reasons for DC or DT on a 7-point Likert scale (1 = not concerned, 7 = extremely concerned). Physicians also provided information regarding treatment decisions from one DC patient, one DT patient, and two current SU users., Results: When asked to report what factors might lead them to DC or DT an SU, physicians reported that hypoglycemic events requiring medical assistance (DC = 6.0, DT = 5.9), hypoglycemic events requiring nonmedical assistance (DC = 5.9, DT = 5.9), other hypoglycemic events not requiring assistance (DT = 5.7), and treatment goals not being met (DC = 5.6) were most concerning. DC and DT patients were more likely to have experienced ≥ 1 hypoglycemic events in the previous year vs. current users (DC = 41.0%, DT = 43.1%, current = 8.8%; p < .05)., Conclusions: Results highlight the strong influence  of hypoglycemia on physicians' decisions to DC or DT SU therapy.

Objective: To assess oral antihyperglycemic agents (OAHA) and/or statin treatment initiation in patients with type 2 diabetes (T2D) and time from diagnosis to both types of treatment initiation and intensification., Research Design and Methods: We reviewed 662 retrospective medical records of patients with T2D diagnosed by 31 general practitioner or specialist sites across Mexico, Argentina, and Brazil. Demographic and clinical information was abstracted from patients' medical records and summarized using descriptive statistics. Between-group differences were assessed with Student's t -test for continuous variables and Fisher's exact test for categorical variables. The starting time of each therapy (OAHA and statins, separately) was assessed using Kaplan-Meier estimates., Results: At diagnosis, patients' mean age was 53 years; 44% had hypertension, 42% were obese, and 23% had dyslipidemia. During the 2-year follow-up, 95% of patients received OAHAs but only 29% of those eligible for statins received this prescription. Mean ± SD and median (Q1, Q3) time to first OAHA was 59 ± 141 days and 1 (1, 31) day, respectively, and 230 ± 232 days and 132 (30, 406) days, respectively, for a statin. During follow-up, 51-53% of patients with HbA1c/FPG values above target did not intensify hyperglycemia treatment., Conclusion: Dyslipidemia treatment in patients with T2D was delayed despite its known deleterious effect on atherosclerosis development and β-cell mass/function. Anti-hyperglycemic treatment was not intensified when targets were not attained. This prescriptive inertia needs to be corrected because attainment of HbA1c treatment goals becomes more difficult, favoring the development of diabetes complications.

Aim: Data on prevalence of chronic kidney disease (CKD) among US adults with type 2 diabetes (T2D) and cardiovascular diseases (CVD) are limited. The aim of this study was to provide such estimates for T2D, both overall and in those with CVD., Materials and Methods: Using the NHANES 2007-2014 data, we conducted a cross-sectional analysis of an adult sample with diagnosed and undiagnosed T2D, aged ≥18 years. CVD was defined based on self-reported personal interview data on a broad range of health conditions-congestive heart failure, coronary heart disease, angina, stroke, or heart attack. T2D was defined as diagnosed T2D (self-reported provider diagnosis) and undiagnosed T2D (FPG ≥126 mg/dL or HbA1c ≥ 6.5% without self-reported diagnosis). Participants who started insulin within a year of T2D diagnosis, or were pregnant at the time of health examination were excluded. Appropriate sample weights were used to provide a national estimate., Results: The prevalence of moderate to severe renal impairment based on eGFR below 60 ml/min/1.73 m 2 among T2D was 18.0%. The prevalence of mild renal impairment was 36.9%: 28.3% with UACR<30 mg/g, 7.0% with UACR ≥30-300 mg/g and 1.6% with UACR >300 mg/g. For T2D and CVD subgroup, the prevalence was 33.6% for moderate to severe renal impairment and 42.8% for mild renal impairment., Conclusions: This study confirms the high prevalence of CKD in patients with multiple comorbidities: T2D and CVD. It also provides estimates of the prevalence of CKD categories based on KDIGO 2012 classification for US adults with T2D., (Copyright © 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.)