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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.)

Type 2 diabetes mellitus (T2DM) is the world's most common metabolic disease. The development of T2DM is mainly caused by a combination of two factors: the failure of insulin secretion by the pancreatic β-cells and the inability of insulin-sensitive tissues to respond to insulin (insulin resistance); therefore, the disease is indicated by a chronic increase in blood glucose. T2DM patients can be treated with mono- or combined therapy using oral antidiabetic drugs and insulin-replaced agents; however, the medication often leads to various discomforts, such as abdominal pain, diarrhea or constipation, nausea and vomiting, and hypersensitivity reactions. A biguanide drug, metformin, has been used as a first-line drug to reduce blood sugar levels. Sulfonylureas work by blocking the ATP-sensitive potassium channel, directly inducing the release of insulin from pancreatic β-cells and thus decreasing blood glucose concentrations. However, the risk of the failure of sulfonylurea as a monotherapy agent is greater than that of metformin or rosiglitazone (a thiazolidinedione drug). Sulfonylureas are used as the first-line drug of choice for DM patients who cannot tolerate metformin therapy. Other antidiabetic drugs, thiazolidinediones, work by activating the peroxisome proliferator-activated receptor gamma (PPARγ), decreasing the IR level, and increasing the response of β-cells towards the glucose level. However, thiazolidines may increase the risk of cardiovascular disease, weight gain, water retention, and edema. This review article aims to discuss case reports on the use of metformin, sulfonylureas, and thiazolidinediones in DM patients. The literature search was conducted on the PubMed database using the keywords 'metformin OR sulfonylureas OR thiazolidinediones AND case reports', filtered to 'free full text', 'case reports', and '10 years publication date'. In some patients, metformin may affect sleep quality and, in rare cases, leads to the occurrence of lactate acidosis; thus, patients taking this drug should be monitored for their kidney status, plasma pH, and plasma metformin level. Sulfonylureas and TZDs may cause a higher risk of hypoglycemia and weight gain or edema due to fluid retention. TZDs may be associated with risks of cardiovascular events in patients with concomitant T2DM and chronic obstructive pulmonary disease. Therefore, patients taking these drugs should be closely monitored for adverse effects.

Background: Patients with diabetes are more likely to suffer COVID-19 complications. Using noninsulin antihyperglycemic medications (AGMs) during COVID-19 infection has proved challenging. In this study, we evaluate different noninsulin AGMs in patients with COVID-19., Methods: We searched Medline, Embase, Web of Science, and Cochrane on 24 January 2022. We used the following keywords (COVID-19) AND (diabetes mellitus) AND (antihyperglycemic agent). The inclusion criteria were studies reporting one or more of the outcomes. We excluded non-English articles, case reports, and literature reviews. Study outcomes were mortality, hospitalization, and intensive care unit (ICU) admission., Results: The use of metformin rather than other glucose-lowering medications was associated with statistically significant lower mortality (risk ratio [RR]: 0.60, 95% confidence interval [CI]: 0.47, 0.77, p < .001). Dipeptidyl peptidase-4 inhibitor (DPP-4i) use was associated with statistically significantly higher hospitalization risk (RR: 1.44, 95% CI: 1.23, 1.68, p < .001) and higher risk of ICU admissions and/or mechanical ventilation vs nonusers (RR: 1.24, 95% CI: 1.04, 1.48, p < .02). There was a statistically significant decrease in hospitalization for SGLT-2i users vs nonusers (RR: 0.89, 95% CI: 0.84-0.95, p < .001). Glucagon-like peptide-1 receptor agonist (GLP-1RA) use was associated with a statistically significant decrease in mortality (RR: 0.56, 95% CI: 0.42, 073, p < 0.001), ICU admission, and/or mechanical ventilation (RR: 0.79, 95% CI: 0.69-0.89, p < .001), and hospitalization (RR: 0.73, 95% CI: 0.54, 0.98, p = .04)., Conclusions: AGM use was not associated with increased mortality. However, metformin and GLP-1RA use reduced mortality risk statistically significantly. DPP-4i use was associated with a statistically significant increase in the risk of hospitalization and admission to the ICU., (© 2023 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Dipeptidyl peptidase-IV (DPP-IV) inhibitors, often known as gliptins, have been used to treat type 2 diabetes mellitus (T2DM). They may be combined with other medications as an additional treatment or used alone as a monotherapy. In addition to insulin, sulfonylureas, thiazolidinediones, and metformin, these molecules appear as possible therapeutic options. Oxadiazole rings have been employed in numerous different ways during drug development efforts. It has been shown that including them in the pharmacophore increases the amount of ligand that may be bound. The exceptional hydrogen bond acceptor properties of oxadiazoles and the distinct hydrocarbon bonding potential of their regioisomers have been established. Beside their anti-diabetic effects, oxadiazoles display a wide range of pharmacological properties. In this study, we made the assumption that molecules containing oxadiazole rings may afford a different approach to the treatment of diabetes, not only for controlling glycemic levels but also for preventing atherosclerosis progression and other complications associated with diabetes. It was observed that oxadiazole fusion with benzothiazole, 5-(2,5,2-trifluoroethoxy) phenyl, β-homophenylalanine, 2-methyl-2-{5-(4-chlorophenyl), diamine-bridged bis -coumarinyl, 5-aryl-2-(6'-nitrobenzofuran-2'-yl), nitrobenzofuran, and/or oxindole leads to potential anti-diabetic activity.

Type 2 diabetes mellitus (T2DM) is an important risk factor for dementia. The possibility to mitigate this risk by controlling T2DM is compelling; however, different glucose-lowering drugs have different effects on the brain by virtue of their different mechanisms of action. The clinical and epidemiological data appear mixed, warranting careful critical evaluation of the human studies. Here we examine the evidence in the context of dementia prevention and treatment, both for people with and without T2DM. We discuss the evidence on this scaffold of research directions, identifying methodological complexities in the extant literature (e.g. comparator discrepancies, changes in the therapeutic landscape), and the implications of different outcome measures (e.g. neuropsychological). We consider possible implications of cerebrovascular protection vs. effects on progression of neurodegenerative proteinopathy, and we present a research roadmap for glucose-lowering drugs in cognitive neurology, including neuroimaging, and fluid biomarkers. We conclude that there is great potential to advance personalized strategies to prevent and treat dementia with glucose-lowering drugs., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Aims: Cardiovascular effects of dipeptidyl peptidase-4 inhibitors (DPP4i) versus sulfonylureas (SU) remain controversial in observational studies. This study aimed to evaluate the influence of DPP4i on major adverse cardiovascular events (MACEs), including acute myocardial infarction, cerebrovascular disease, heart failure, cardiogenic shock, malignant dysrhythmia, and revascularisation., Materials and Methods: We conducted a nationwide cohort study using claims data from the National Health Insurance in Taiwan from 2007 to 2013. We enrolled type 2 diabetes patients who received DPP4i or SU in addition to metformin. DPP4i users were matched to SU users using propensity scores at a ratio of 1:1. The study outcomes were hospitalisation for MACE, heart failure, acute myocardial infarction, cerebrovascular disease, coronary revascularisation, and hypoglycaemia., Results: There were 37,317 matched pairs of DPP4i and SU users with a mean follow-up of 2.1 years. Compared with SU users, DPP4i users showed a significantly lower risk of hospitalisation for MACE (HR 0.79 [95% CI 0.75-0.82]), heart failure (0.86 [0.79-0.93]), acute myocardial infarction (0.76 [0.68-0.92]), and cerebrovascular disease (0.72 [0.67-0.77]). Both sitagliptin (0.89 [0.85-0.94]) and vildagliptin ([0.77 [0.60-0.99]) showed a significantly lower risk of hospitalisation for MACE, but saxagliptin showed a borderline significantly higher risk of hospitalisation for heart failure (1.59 [1.00-2.55])., Conclusions: DPP4i showed better cardioprotective effects than SU, especially among patients receiving sitagliptin or vildagliptin., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Metformin is hypothesized to protect against the risk of venous thromboembolism (VTE); however, there is a paucity of data supporting this hypothesis. Among individuals aged 40-90 years with a diagnosis of type 2 diabetes in the Health Improvement Network database (2000-2019), we compared the risks of incident VTE, pulmonary embolism, and deep vein thrombosis among metformin initiators with those among sulfonylurea initiators. Individuals were followed from their first prescription refill to an incident VTE, drug discontinuation, switching or augmenting, plan disenrollment, or the end of the study, whichever occurred first. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox model, adjusting for confounders using inverse probability of treatment weighting. Among 117,472 initiators of metformin and 13,835 initiators of sulfonylureas, 555 (1.3/1,000 person-years) and 75 (2.1/1,000 person-years) VTE cases occurred in each group, respectively. The multivariable-adjusted HR was 0.65 (95% CI: 0.51, 0.84). The corresponding risks for pulmonary embolism (adjusted HR = 0.71, 95% CI: 0.50, 1.01) and deep vein thrombosis (adjusted HR = 0.64, 95% CI: 0.48, 0.87) were also lower in metformin initiators than in sulfonylurea initiators. Our study provided empirical evidence to support a lower risk of VTE after initiation of metformin as compared with sulfonylureas among patients with type 2 diabetes., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Antidiabetic medications (ADM), especially sulfonylureas (SFU) and basal insulin (BI), are associated with increased risk of hypoglycemia, which is especially concerning among older adults in poor health. The objective of this study was to investigate prescribing patterns of ADM in older adults according to their health status., Methods: This case control study analyzed administrative claims between 2013 and 2017 from a large national payer. The study population was derived from a nationwide database of 84,720 U.S. adults aged ≥65, who were enrolled in Medicare Advantage health insurance plans. Participants had type 2 diabetes on metformin monotherapy, and started a second-line ADM during the study period. The exposure was a binary variable for health status, with poor health defined by end-stage medical conditions, dementia, or residence in a long-term nursing facility. The outcome was a variable identifying which second-line ADM class was started, categorized as SFU, BI, or other (i.e. all other ADM classes combined)., Results: Over half of participants (54%) received SFU as initial second-line ADM, 14% received BI, and 32% received another ADM. In multivariable models, the odds of filling SFU or BI was higher for participants in poor health than those in good or intermediate health [OR 1.13 (95% CI 1.05-1.21) and OR 2.34 (95% CI 2.14-2.55), respectively]. SFU and BI were also more commonly filled by older adults with poor glycemic control., Conclusions: Despite clinical consensus to use caution prescribing SFU and BI among older adults in poor health, these medications remain frequently used in this particularly vulnerable population., (© 2022. The Author(s).)

Introduction: Type 2 diabetes (T2D) is increasingly prevalent and associated with increased risk for cardiovascular and renal disease. After lifestyle modification, metformin is usually the first-line pharmacotherapy and sulfonylureas are traditionally added after metformin failure. However, with newer glucose lowering drugs that may have less risk of hypoglycemia or that may reduce cardiovascular and renal events, the position of sulfonylureas is being reevaluated., Areas Covered: In this article, the authors review relevant publications related to the use of sulfonylureas., Expert Opinion: Sulfonylureas are potent glucose lowering drugs. The risk of hypoglycemia varies with different drugs within the class and can be minimized by using the safer drugs, possibly in lower doses. Cardiovascular events do not appear to be increased with some of the newer generation drugs. The durability of glycemic control also appears comparable to other newer agents. Sulfonylureas are the preferred treatment for some types of monogenic diabetes and selection of T2D patients who may have greater benefit from sulfonylureas based on certain phenotypes and genotypes is likely to be refined further by precision medicine. Sulfonylureas are inexpensive and readily available everywhere and they are still the most frequently used second-line treatment for T2D in many parts of the world.

Aims: Type 2 diabetes mellitus (T2DM) is a strong risk factor for complications of coronavirus disease 2019 (COVID-19). The effect of T2DM medications on COVID-19 outcomes remains unclear. In a retrospective analysis of a cohort of 131 patients with T2DM hospitalized for COVID-19 in Wuhan, we have previously found that metformin use prior to hospitalization is associated with reduced mortality. The current study aims to investigate the effects of inpatient use of T2DM medications, including metformin, acarbose, insulin and sulfonylureas, on the mortality of COVID-19 patients with T2DM during hospitalization., Methods: We continue to carry out a retrospective analysis of a cohort of 131 patients with T2DM hospitalized for COVID-19 and treated with different combinations of diabetes medications., Results: We found that patients using metformin (p = .02) and acarbose (p = .04), alone or both together (p = .03), after admission were significantly more likely to survive than those who did not use either metformin or acarbose. 37 patients continued to take metformin after admission and 35 (94.6%) survived. Among the 57 patients who used acarbose after admission, 52 survived (91.2%). A total of 20 patients used both metformin and acarbose, while 57 used neither. Of the 20 dual-use patients, 19 (95.0%) survived., Conclusion: Our analyses suggest that inpatient use of metformin and acarbose together or alone during hospitalization should be studied in randomized trials., (© 2021 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Objective: Gestational Diabetes Mellitus (GDM) and Type 2 Diabetes Mellitus (DM2) are metabolic disorders characterized by increased insulin resistance. Although insulin is the treatment of choice in pregnant patients with DM, the prescription of oral hypoglycemic agents (OHA) has been increasing among practitioners. This study aimed to evaluate the maternal and neonatal outcomes when oral hypoglycemic agents were used in diabetic pregnant women., Methods: Medical records from the Maternal-Infant Care Unit Clinics SoM-UPR (n=149) were reviewed. Patients that were treated with metformin, sulfonylurea or insulin were included. Maternal and neonatal outcomes were compared between groups., Results: Patient's mean age was 28 ± 6 years. The majority had GDM (91%). The most common comorbidity was hypertension (9.9%). Lifestyle modification was used as treatment in 77% of patients during the second trimester, but its use decreased to 33% during the third trimester. Insulin was the treatment of choice. Among the OHA, sulfonylurea was preferred. Postprandial glucose levels were lower in patients who used insulin as compared to those without medications., Conclusion: No significant differences were found in maternal outcomes such as C-section, induction of labor, episiotomy or preterm labor, or neonatal outcomes such as macrosomia, neonatal hypoglycemia or congenital abnormalities among treatment groups. OHA can be considered as an alternative to insulin for the treatment of DM during pregnancy in selected cases.

Aim: To assess cardiovascular (CV) events and all-cause mortality in type 2 diabetes mellitus (T2DM) patients treated with first-line monotherapies of non-insulin antidiabetic drugs (NIADs)., Methods: Longitudinal retrospective cohort study in the Catalan database SIDIAP (Information System for the Development of Research in Primary Care). T2DM patients ≥18 years newly prescribed first-line monotherapies during 2010-2015 were followed since their first prescription until the composite of major adverse CV events, MACE (myocardium infarction [MI], stroke and all-cause death), its components, heart failure (HF) and peripheral artery disease (PAD) or censoring. Cox proportional hazard models were used to estimate hazard ratios 95% confidence interval (HR [95%CI])., Results: Compared with metformin, the use of sulfonylureas, dipeptidyl peptidase-4 inhibitors (DPP-4 i) and meglitinides were significantly associated with higher risk for MACE (1.55 [1.42-1.68]); 1.49 [1.22-1.84] and 2.01 [1.29-3.12]) and all-cause mortality (1.67 [1.52-1.84], 1.65 [1.30-2.] and 2.08 [1.26-3.42]). Sulfonylureas users had increased risk of MI (1.38 [1.03-1.85]) stroke (1.31 [1.11-1.54]), HF (1.49 [1.28-1.72]) and PAD (1.24 [1.02-1.51]). Meglitinides users were at increased risks of MI, HR 2.03 (1.10-3.74)., Conclusion: In first-line monotherapies, compared with metformin, sulfonylureas were associated with increased risks in all the outcomes; DPP-4 i and repaglinide showed increased risks of MACE and mortality. Residual confounding cannot be ruled out., (Copyright © 2020 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

There is a universal agreement that when lifestyle modifications are inadequate to control the hyperglycemia, metformin should be considered the first line of pharmacological therapy. However, when metformin monotherapy fails, there is no consensus as to which drug should be added. Many new classes of drugs that are currently available including DPP-4 inhibitors, GLP-1 agonists and SGLT-2 inhibitors have undergone cardiovascular outcome trials which had been made mandatory by the regulatory authority and thereby established their cardiovascular safety or at least neutrality. Though sulfonylureas are one of the widely prescribed drugs both in developed and developing countries and have proven their efficacy for glycemic control and prevention of microvascular complications, there is considerable uncertainty about its cardiovascular safety which has been going on for nearly five decades. In this review, we will critically analyze the efficacy and cardiovascular safety of sulphonylureas, based on the latest available literature to clarify their role in our day-to-day clinical practice., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aims: To compare the effectiveness and safety of gliclazide modified release (MR) to sitagliptin as type 2 diabetes mellitus (T2D) treatments in a real-world patient population., Materials and Methods: This retrospective cohort study used records from the UK Clinical Practice Research Datalink. The cohort consisted of adult patients with T2D newly treated with either gliclazide MR or sitagliptin as second-line treatment added to metformin and with a glycated haemoglobin (HbA1c) level of ≥7.0% (53 mmol/mol). Patients were 1:1 matched using high-dimensional propensity score matching and followed to determine the time taken to reach an HbA1c <7.0%. Secondary outcomes included time to HbA1c ≤6.5% (48 mmol/mol), time to ≥1% (11 mmol/mol) HbA1c reduction from baseline, treatment persistence and durability, and hypoglycaemic events., Results: Among the 1986 patients included, those on gliclazide MR more likely achieved an HbA1c <7.0% [hazard ratio (HR): 1.35; 95% confidence interval (CI): 1.15-1.57], HbA1c ≤6.5% (HR: 1.51; 95% CI: 1.19-1.92) or had an HbA1c reduction ≥1% from baseline (HR: 1.11; 95% CI: 1.00-1.24) compared with patients on sitagliptin. Durability (log-rank P = .135) and persistence (P = .119) were similar between the two groups. Hypoglycaemic events were uncommon (23 total severe and non-severe events; incidence rate, 3.7 per 1000 patient years), with 4.7 and 2.6 events per 1000 patient years with gliclazide MR and sitagliptin treatment, respectively., Conclusions: In this real-world study, second-line gliclazide MR was more effective than sitagliptin in reducing HbA1c, with similar durability and persistence and low rates of hypoglycaemic events, in individuals with T2D on metformin treatment and HbA1c above the target of 7.0%., (© 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Type 2 diabetes mellitus (T2D) is a chronic metabolic disease resulting from insulin resistance and progressively reduced insulin secretion, which leads to impaired glucose utilization, dyslipidemia and hyperinsulinemia and progressive pancreatic beta cell dysfunction. The incidence of type 2 diabetes mellitus is increasing worldwide and nowadays T2D already became a global epidemic. The well-known interindividual variability of T2D drug actions such as biguanides, sulfonylureas/meglitinides, DPP-4 inhibitors/GLP1R agonists and SGLT-2 inhibitors may be caused, among other things, by genetic factors. Pharmacogenetic findings may aid in identifying new drug targets and obtaining in-depth knowledge of the causes of disease and its physiological processes, thereby, providing an opportunity to elaborate an algorithm for tailor or precision treatment. The aim of this article is to summarize recent progress and discoveries for T2D pharmacogenetics and to discuss the factors which limit the furthering accumulation of genetic variability knowledge in patient response to therapy that will allow improvement the personalized treatment of T2D.

Background: According to the World Health Organization (WHO), diabetes mellitus is considered the 7th leading cause of death as of 2016, while almost half of all deaths related to high blood glucose occur before the age of 70. According to the 2019 American Diabetes Association's (ADA) guidelines, metformin is the firstline treatment for patients with Type 2 diabetes. Additional therapy is dependent on multiple patient-specific factors, including cardiovascular risks, risk of hypoglycemia, metabolic changes, and cost. The objective of this systematic review is to analyze variables of interest in Type 2 diabetes including fasting blood glucose (FBG), post-prandial blood glucose (PPBG), hemoglobin A1c (HbA1c), microvascular complications, and cardiovascular outcomes in order to determine the shift towards the newer class of medications for type 2 diabetes., Methods: A systematic review was conducted using ScienceDirect as the primary source of obtaining articles. This review used PRISMA for reporting and GRACE for quality assessment of ten articles. The inclusion criteria for the review consisted of patients who were on metformin therapy for a sufficient amount of time, as defined by the trial's protocol, and who were then initiated on either a sulfonylurea (glipizide or glimepiride) or a DPP-4 inhibitor (saxagliptin or linagliptin). The articles included in this review range from 2005-2019 that are written in English only. Exclusion criteria for this systematic review were articles in which patients were not initially started on metformin therapy, were diagnosed with Type 1 diabetes mellitus, and articles that were written in languages other than English., Results: After filtering 50 studies, 10 were selected for meeting the criteria of variables of interest. Findings suggested a significant reduction in fasting plasma glucose with 154 mg/dL + 4 mg/dL as baseline, decreasing to 132 mg/dL + 4 mg/dL with the use of glipizide & metformin combination. A similar pattern was presented with the use of saxagliptin and metformin in combination, but changes were less significant than glipizide. However, hypoglycemic events in patients who were taking glipizide with metformin versus saxagliptin with metformin; 13.4% of patients achieved HbA1c <7% without hypoglycemic events compared to 22.2% of the patients who achieved an HbA1c of <7% without hypoglycemic events., Conclusion: Despite the higher efficacious characteristics of sulfonylureas in lowering HbA1c, due to its reported hypoglycemic effects, DPP-4 inhibitors may be considered as a clinically stable choice for second-line therapy after completing maximally tolerated doses of metformin. Sulfonylureas are considered better than DPP-4 inhibitors for treatment in patients with cardiovascular disease history and hypoglycemia., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: Type 2 diabetes is a complex genetic disorder, and a large number of genetic polymorphisms may be involved in its pathogenesis. Pharmacologically, type 2 diabetes can be treated with 9 different approved classes of drugs, but metformin is suggested as the first line of therapy, followed by sulfonylureas., Methods: This was a case-control study consisting of 300 metformin responders and 300 metformin nonresponders in patients with type 2 diabetes and 300 healthy Pakistani subjects. Genotyping of the SLC22A3 G>A polymorphism was performed by allele-specific polymerase chain reaction (PCR) for microRNA 147 expression; real-time polymerase chain reaction was used, and expressional analysis of SLC22A3 was done by semiquantitative polymerase chain reaction., Results: GA and AA genotypes were highly significantly associated with the drug treatments when compared with controls. A statistically significant difference was observed in the distribution of the SLC22A3 A allele between healthy subjects and patients with type 2 diabetes. When odds ratios were adjusted for glycated hemoglobin levels and postprandial and fasting blood glucose levels, our findings showed that the overexpression of allele A of the rs3088442 G>A variant may act as a protective allele and is associated with the clinical response to metformin. microRNA 147 expression was found to be increased in patients who were metformin responders compared with the nonresponder group and controls. mRNA expression of SLC22A3 was significantly reduced in patients taking metformin as compared to other groups., Conclusions: These results suggested that the SLC22A3 rs3088442 at position 2282 A allele may confer metformin clinical responses in patients with type 2 diabetes in the Pakistani population. Overexpression of microRNA 147 is associated with a downward expression of the SLC22A3 gene in patients who have type 2 diabetes., (Copyright © 2018 Diabetes Canada. Published by Elsevier Inc. All rights reserved.)

Purpose: Several observational studies suggest that metformin reduces incidence cancer risk; however, many of these studies suffer from time-related biases and several cancer outcomes have not been investigated due to small sample sizes., Methods: We constructed a propensity score-matched retrospective cohort of 84,434 veterans newly prescribed metformin or a sulfonylurea as monotherapy. We used Cox proportional hazard regression to assess the association between metformin use compared to sulfonylurea use and incidence cancer risk for 10 solid tumors. We adjusted for clinical covariates including hemoglobin A1C, antihypertensive and lipid-lowering medications, and body mass index. Incidence cancers were defined by ICD-9-CM codes., Results: Among 42,217 new metformin users and 42,217 matched-new sulfonylurea users, we identified 2,575 incidence cancers. Metformin was inversely associated with liver cancer (adjusted hazard ratio [aHR] = 0.44, 95% CI 0.31, 0.64) compared to sulfonylurea. We found no association between metformin use and risk of incidence bladder, breast, colorectal, esophageal, gastric, lung, pancreatic, prostate, or renal cancer when compared to sulfonylurea use., Conclusions: In this large cohort study that accounted for time-related biases, we observed no association between the use of metformin and most cancers; however, we found a strong inverse association between metformin and liver cancer. Randomized trials of metformin for prevention of liver cancer would be useful to verify these observations.

Background: Metformin and the sulfonylureas are common initial antidiabetic agents; the former has demonstrated anti-TB action in in vitro and animal studies. The comparative effect of metformin vs the sulfonylureas on TB risk in patients with type 2 diabetes mellitus (T2DM) remains unclear., Methods: In this retrospective cohort study, patients without chronic kidney disease who received a T2DM diagnosis during 2003 to 2013 were identified from the Taiwan National Health Insurance Research Database. Participants with ≥ 2 years of follow-up were reviewed and observed for TB until December 2013. Patients receiving metformin ≥ 60 cumulative defined daily dose (cDDD) and sulfonylureas < 15 cDDD in the initial 2 years were defined as metformin majors; it was the inverse for sulfonylurea majors. The two groups were matched 1:1 by propensity score and compared for TB risk by multivariate Cox regression analysis., Results: Among 40,179 patients with T2DM, 263 acquired TB (0.65%) over a mean follow-up of 6.1 years. In multivariate analysis, the initial 2-year dosage of metformin, but not that of the sulfonylureas, was an independent predictor of TB (60-cDDD increase (adjusted hazard ratio [HR], 0.931; 95% CI, 0.877-0.990) after adjustment by cofactors, including adapted diabetes complication severity index. Metformin majors had a significantly lower TB risk than that of sulfonylurea majors before and after matching (HR, 0.477; 95% CI, 0.268-0.850 and HR, 0.337; 95% CI, 0.169-0.673; matched pairs, n = 3,161). Compared with the reference group (initial 2-year metformin < 60 cDDD), metformin treatment showed a dose-dependent association with TB risk (60-219 cDDD; HR, 0.860; 95% CI, 0.637-1.161; 220-479 cDDD, HR, 0.706; 95% CI, 0.485-1.028; ≥ 480 cDDD, HR, 0.319; 95% CI, 0.118-0.863)., Conclusions: Metformin use in the initial 2 years was associated with a decreased risk of TB, and metformin users had a reduced risk compared with their sulfonylurea comparators., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Patients with type 2 diabetes (T2D) typically use several drug treatments during their lifetime. There is a debate about the best second-line therapy after metformin monotherapy failure due to the increasing number of available antidiabetic drugs and the lack of comparative clinical trials of secondary treatment regimens. While prior research compared the cost-effectiveness of two alternative drugs, the literature assessing T2D treatment pathways is scarce. The purpose of this study was to evaluate the long-term cost-effectiveness of dipeptidyl peptidase-4 inhibitors (DPP-4i) compared to sulfonylureas (SU) as second-line therapy in combination with metformin in patients with T2D., Methods: A Markov model was developed with four health states, 1 year cycle, and a 25-year time horizon. Clinical and cost data were collected from previous studies and other readily available secondary data sources. The incremental cost-effectiveness ratio (ICER) was estimated from the US third party payer perspective. Both, costs and outcomes, were discounted at a 3% annual discount rate. One way and probabilistic sensitivity analyses were performed to evaluate the impact of uncertainty on the base-case results., Results: The discounted incremental cost of metformin+DPP-4i compared to metformin+SU was $11,849 and the incremental life-years gained were 0.61, resulting in an ICER of $19,420 per life-year gained for patients in the metformin+DPP-4i treatment pathway. The ICER estimated in the probabilistic sensitivity analysis was $19,980 per life-year gained. Sensitivity analyses showed that the results of the study were not sensitive to changes in the parameters used in base-case., Conclusions: The metformin+DPP-4i treatment pathway was cost-effective compared to metformin+SU as a long-term second-line therapy in the treatment of T2D from the US health care payer perspective. Study findings have the potential to provide clinicians and third party payers valuable evidence for the prescription and utilization of cost-effective second-line therapy after metformin monotherapy failure in the treatment of T2D.

Background: Data are limited regarding adherence to dipeptidyl peptidase-4 inhibitors., Methods: The present retrospective cohort study of a claims database involved adults with type 2 diabetes mellitus, continuous enrollment for 12 months before the first prescription of add-on sitagliptin (SITA) or a sulfonylurea (SU) to metformin (MET) monotherapy (index date), and ≥45 days of MET coverage ≤90 days before the index date. The SITA and SU users were matched on duration of follow-up and propensity score (PS). Logistic regression analysis incorporated age, gender, comorbidities, and concomitant medications as independent variables., Results: Approximately 99 % of SITA patients were PS matched, resulting in 14 807 well-balanced PS-matched SITA/SU pairs. Mean proportion of days covered (PDC) was significantly higher for SITA (vs SU) + MET after 1 year (P < 0.001). Adherence (PDC ≥80 %) to SITA (vs SU) + MET was 59.1 % (vs 55.9 %; P < 0.001) at 1 year and 52.6 % (vs 49.9 %; P = 0.007) at 2 years. Using logistic regression models including out-of-pocket expense (OPE) as a covariate, we found improved mean PDC and adherence for SITA (vs SU) + MET. Numbers of patients who continued to use SITA (vs SU) + MET were significantly higher after Years 1, 2, and 3 (all P < 0.05)., Conclusions: Users of SITA + MET had significantly higher mean PDC, adherence, and persistence than those on SU + MET. These trends were robust to model alterations and were more marked when accommodating OPEs., (© 2016 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, N.J., U.S.A. Journal of Diabetes published by John Wiley & Sons Australia, Ltd and Ruijin Hospital, Shanghai Jiaotong University School of Medicine.)

The article provides an overview of sulfonylureas and meglitinides as second-line agents for treating type 2 diabetes mellitus (T2DM). Implications for occupational health clinicians who work with these individuals when they take either of these medications to achieve target glycemic indices are emphasized., (© 2016 The Author(s).)

Purpose: Growing evidence suggests that certain commonly used diabetes medications have the potential to differentially alter breast cancer risk. We evaluated the influence of metformin, insulin, and sulfonylureas on risk of incident invasive breast cancer., Methods: We conducted a retrospective cohort study of women ≥40 years of age enrolled in a health plan between 1996 and 2011. Ever, current (≤12 months), and duration (<1, 1-2.9, ≥3 years) of diabetes medication use were obtained from pharmacy databases and modeled as time varying. Multivariable Cox proportional hazards models adjusting for potential confounders including screening mammography and body mass index were used to estimate hazard ratios (HRs) and 95% Confidence Intervals (CIs)., Results: Among 10,050 women with diabetes, 57 % used metformin, 43 % used sulfonylureas, 32 % used insulin, and 301 were diagnosed with breast cancer over median follow-up of 6.7 years. Results suggested no significant decreased risk of breast cancer among metformin users (HR 0.86; 95% CI 0.65-1.12). We found no association between increased breast cancer risk and long-acting insulin (HR 0.95; 95% CI 0.51-1.77), but reduced risk with short-/rapid-acting insulin (HR 0.69; 95% CI 0.50-0.94), and suggestion of a dose-response with increasing duration of short-/rapid-acting insulin use (HR 0.87; 95% CI 0.76-1.00). Estimates for sulfonylurea users suggested increased risk with ever use (HR 1.18; 95% CI 0.90-1.53) and with longer durations of use (≥3 years: HR 1.23; 95% CI 0.88-1.73), but confidence intervals included 1.0., Conclusions: Our results provide little support for the previously hypothesized decreased risk of breast cancer with metformin use or for an increased risk with insulin use. Implications for possible residual confounding by screening mammography and comorbidity should be considered in breast cancer pharmacoepidemiology studies.

Background: The aim of the present study was to assess the risk of overall mortality, coronary artery disease (CAD), and congestive heart failure (CHF) in patients with type 2 diabetes mellitus (T2DM) treated with metformin (MF) and an additional antidiabetic agent., Methods: A retrospective cohort study was conducted using an academic health center enterprise-wide electronic health record (EHR) system to identify 13,185 adult patients (>18 years) with T2DM from January 2008 to June 2013 and received a prescription for MF in combination with a sulfonylurea (SU; n = 9419), thiazolidinedione (TZD; n = 1846), dipeptidyl peptidase-4 inhibitor (DPP-4i; n = 1487), or a glucagon-like peptide-1 receptor agonist (GLP-1a; n = 433). Multivariate Cox models with propensity analysis were used to compare cohorts, with MF+SU serving as the comparator group., Results: The mean (±SD) age was 60.6 ± 12.6 years, with 54.6% male and 75.8% Caucasians. The median follow-up was 4 years. There were 1077 deaths, 1733 CAD events, and 528 CHF events in 55,100 person-years of follow-up. A higher risk of CHF was observed with MF+DPP-4i use (hazard ratio [HR] 1.104; 95% confidence interval [CI] 1.04-1.17; P = 0.001). A trend towards improved overall survival for users of MF+TZD (HR 0.86; 95% CI 0.74-1.0; P = 0.05) and MF+GLP-1a (HR 0.569; 95% CI 0.30-1.07; P = 0.08) was observed. No significant differences in the risk of CAD were identified., Conclusions: Consistent with recent studies, our results raise concern for an increased risk of CHF with use of DPP-4i., (© 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

It is unclear whether prior antidiabetic treatment affects stroke severity and outcome. To evaluate this association, we prospectively studied all patients who were admitted in our Department with acute ischaemic stroke (n = 378, mean age = 78.8 ± 6.5 years). The severity of stroke was assessed at admission with the National Institutes of Health Stroke Scale. The outcome was assessed with the modified Rankin Scale at discharge and with in-hospital mortality. A total of 123 patients had type 2 diabetes mellitus. At admission, there was a trend for lower National Institutes of Health Stroke Scale in patients treated with dipeptidyl peptidase 4 inhibitors compared with patients treated with other antidiabetic agents (6.1 ± 7.5 vs 10.0 ± 9.2, respectively; p = 0.079). At discharge, patients treated with dipeptidyl peptidase 4 inhibitors had lower modified Rankin Scale than patients treated with other antidiabetic agents (2.1 ± 1.9 vs 3.2 ± 2.1, respectively; p < 0.05). Patients treated with dipeptidyl peptidase 4 inhibitors also had lower in-hospital mortality than patients treated with other antidiabetic agents (0.0% vs 15.1%, respectively; p < 0.05). In conclusion, prior treatment with dipeptidyl peptidase 4 inhibitors in patients with acute ischaemic stroke appears to be associated with better functional outcome and lower mortality risk., (© The Author(s) 2015.)

Table 3 provides an overview of the oral antihyperglycemic drugs reviewed in this article. A 2011 meta-analysis by Bennett and colleagues found low or insufficient quality of evidence favoring an initial choice of metformin, SUs, glinides, TZDs, or (table see text) DPP-4 inhibitors (alpha-glucosidase inhibitors, bromocriptine mesylate, and SGLT2 inhibitors were not included in this meta-analysis) with regard to the outcomes measures of all-cause mortality, cardiovascular events and mortality, and incidence of microvascular disease (retinopathy, nephropathy, and neuropathy) in previously healthy individuals with newly diagnosed T2DM. Likewise, the Bennett and colleagues meta-analysis judged these drugs to be of roughly equal efficacy with regard to reduction of HbA1c (1%–1.6%) from the pretreatment baseline. The ADOPT clinical trial of 3 different and, at the time, popular, oral monotherapies for T2DM provides support for the consensus recommendation of metformin as first-line therapy. The ADOPT trial showed slightly superior HbA1c reduction for rosiglitazone compared with metformin, which was in turn superior to glyburide. However, significant adverse events, including edema, weight gain, and fractures, were more common in the rosiglitazone-treated patients. The implication of this trial is that the combination of low cost, low risk, minimal adverse effects, and efficacy of metformin justifies use of this agent as the cornerstone of oral drug treatment of T2DM. Judicious use of metformin in groups formerly thought to be at high risk for lactic acidosis (ie, those with CHF, chronic kidney disease [eGFR >30 mL/min/1.73 m2], and the elderly) may be associated with mortality benefit rather than increased risk. Secondary and tertiary add-on drug therapy should be individualized based on cost, personal preferences, and overall treatment goals, taking into account the wishes and priorities of the patient., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background and Aim: Chronic kidney disease (CKD) is frequent in type 2 diabetes mellitus (T2DM), and therapeutic management of diabetes is more challenging in patients with renal impairment (RI). The place of metformin is of particular interest since most scientific societies now recommend using half the dosage in moderate RI and abstaining from use in severe RI, while the classic contraindication with RI has not been removed from the label. This study aimed to assess the therapeutic management, in particular the use of metformin, of T2DM patients with CKD in real life., Methods: This was a French cross-sectional observational study: 3,704 patients with T2DM diagnosed for over 1 year and pharmacologically treated were recruited in two cohorts (two-thirds were considered to have renal disease [CKD patients] and one-third were not [non-CKD patients]) by 968 physicians (81% general practitioners) in 2012., Results: CKD versus non-CKD patients were significantly older with longer diabetes history, more diabetic complications, and less strict glycemic control (mean glycated hemoglobin [HbA(1c)] 7.5% versus 7.1%; 25% of CKD patients had HbA1c ≥8% versus 15% of non-CKD patients). Fifteen percent of CKD patients had severe RI, and 66% moderate RI. Therapeutic management of T2DM was clearly distinct in CKD, with less use of metformin (62% versus 86%) but at similar mean daily doses (~2 g/d). Of patients with severe RI, 33% were still treated with metformin, at similar doses. For other oral anti-diabetics, a distinct pattern of use was seen across renal function (RF): use of sulfonylureas (32%, 31%, and 20% in normal RF, moderate RI, and severe RI, respectively) and DPP4-i (dipeptidyl peptidase-4 inhibitors) (41%, 36%, and 25%, respectively) decreased with RF, while that of glinides increased (8%, 14%, and 18%, respectively). CKD patients were more frequently treated with insulin (40% versus 16% of non-CKD patients), and use of insulin increased with deterioration of RF (19%, 39%, and 61% of patients with normal RF, moderate RI, and severe RI, respectively). Treatment was modified at the end of the study-visit in 34% of CKD patients, primarily to stop or reduce metformin. However, metformin was stopped in only 40% of the severe RI patients., Conclusion: Despite a fairly good detection of CKD in patients with T2DM, RI was insufficiently taken into account for adjusting anti-diabetic treatment.

Context Low-dose sulfonylureas (SUs) have been found to augment the classical incretin effect, increase glucose sensitivity and late phase incretin potentiation. Objective To evaluate potential synergy between low-dose SU plus a dipeptidyl peptidase 4 (DPP4) inhibitor. Methods Unblinded randomized crossover study at the Clinical Research Centre, University of Dundee. Thirty participants with T2DM (HbA1c < 64 mmol/mol) were treated with diet or metformin. Participants completed 4, 14-day blocks in a random order: control, gliclazide 20 mg (SU), sitagliptin 100 mg (DPP4 inhibitor [DPP4i]), or combination (SUDPP4i). A mixed meal test was conducted after each intervention. The primary outcome was the effect of treatment on beta-cell glucose sensitivity. Secondary outcomes included frequency of glucose <3 mmol/L on continuous glucose monitoring, subanalyses by genotype (KNCJ11 E23K), gender, and body mass index. Results SU combination with DPP4i showed additive effect on glucose lowering: mean glucose area under the curve (mean 95% CI) (mmol/L) was control 11.5 (10.7-12.3), DPP4i 10.2 (9.4-11.1), SU 9.7 (8.9-10.5), SUDPP4i 8.7 (7.9-9.5) (P <.001). Glucose sensitivity mirrored the additive effect (pmol min−1 m−2 mM−1): control 71.5 (51.1-91.9), DPP4i 75.9 (55.7-96.0), SU 86.3 (66.1-106.4), SUDPP4i 94.1 (73.9-114.3) (P =.04). The additive effect was seen in men but not women. Glucose time in range <3 mmol/L on continuous glucose monitoring (%) was unaffected: control 1 (2-4), DPP4i 2 (3-6), SU 1 (0-4), SUDPP4i 3 (2-7) (P =.65). Conclusion Low-dose sulfonylurea plus DPP4i has a potent glucose-lowering effect through augmentation of beta-cell function. A double-blind randomized controlled trial would formalize efficacy and safety of this combination, which may avoid negative aspects of SU. [ABSTRACT FROM AUTHOR]

Distributed network studies and multisite studies assess drug safety and effectiveness in diverse populations by pooling information. Targeting groups of clinical or policy interest (including specific sites or site combinations) and applying weights based on effect measure modifiers (EMMs) prior to pooling estimates within multisite studies may increase interpretability and improve precision. We simulated a 4-site study, standardized each site using inverse odds weights (IOWs) to resemble the 3 smallest sites or the smallest site, estimated IOW-weighted risk differences (RDs), and combined estimates with inverse variance weights (IVWs). We also created an artificial distributed network in the Clinical Practice Research Datalink (CPRD) Aurum consisting of 1 site for each geographic region. We compared metformin and sulfonylurea initiators with respect to mortality, targeting the smallest region. In the simulation, IOWs reduced differences between estimates and increased precision when targeting the 3 smallest sites or the smallest site. In the CPRD Aurum study, the IOW + IVW estimate was also more precise (smallest region: RD = 5.41% [95% CI, 1.03-9.79]; IOW + IVW estimate: RD = 3.25% [95% CI, 3.07-3.43]). When performing pharmacoepidemiologic research in distributed networks or multisite studies in the presence of EMMs, designation of target populations has the potential to improve estimate precision and interpretability. This article is part of a Special Collection on Pharmacoepidemiology. [ABSTRACT FROM AUTHOR]

Background: Due to increasing life expectancy, almost half of people with type 2 diabetes are aged 65 years or over worldwide. When metformin alone does not control blood sugar, the choice of which second-line therapy to prescribe next is not clear from currently available evidence. The existence of frailty and comorbidities in older adults further increases the complexity of medical decision-making. As only a relatively small proportion of trials report results separately for older adults, the relative efficacy and safety of second-line therapies in older adults with type 2 diabetes mellitus are unknown and require further investigation. This individual participant data (IPD) network meta-analysis evaluates the relative efficacy and safety of second-line therapies on their own or in combination in older adults with type 2 diabetes mellitus. Methods: All relevant published and unpublished trials will be identified. Studies published prior to 2015 will be identified from two previous comprehensive aggregate data network meta-analyses. Searches will be conducted in CENTRAL, MEDLINE, and EMBASE from 1st January 2015 onwards, and in clinicaltrials.gov from inception. Randomised controlled trials with at least 100 estimated older adults (≥ 65 years) receiving at least 24 weeks of intervention that assess the effects of glucose-lowering drugs on mortality, glycemia, vascular and other comorbidities outcomes, and quality of life will be eligible. The screening and data extraction process will be conducted independently by two researchers. The quality of studies will be assessed using the Cochrane risk of bias tool 2. Anonymised IPD of all eligible trials will be requested via clinical trial portals or by contacting the principal investigators or sponsors. Received data will be reanalysed where necessary to standardise outcome metrics. Network meta-analyses will be performed to determine the relative effectiveness of therapies. Discussion: With the increasing number of older adults with type 2 diabetes worldwide, an IPD network meta-analysis using data from all eligible trials will provide new insights into the optimal choices of second-line antidiabetic drugs to improve patient management and reduce unnecessary adverse events and the subsequent risk of comorbidities in older adults. Systematic review registration: PROSPERO CRD42021272686. [ABSTRACT FROM AUTHOR]

Purpose: The current umbrella review aimed to evaluate the effect of metformin on all-cause mortality (ACM), cardiovascular mortality, and cardiovascular disease (CVD) incidence in DM patients. Methods: PubMed, Scopus, Cochrane, Google Scholar, and Web of Science databases were searched with special keywords. Related studies were included after screening by two independent investigators based on title and full texts. The AMSTAR2 checklist was used to assess the quality of studies, and Cochran tests were used to assess the heterogeneity between studies. Overall, seventeen systematic reviews and meta-analysis studies were included. The results revealed that the risk of ACM in patients who received metformin was lower than in patients who did not receive metformin. (OR: 0.80, 95% CI:0.744,0.855); also, the risk of CVD mortality in metformin patients was lower than in the other two groups (placebo and other anti-diabetic drugs) (OR: 0.771, 95% CI:0.688,0.853, P:0.001). The risk of CVD in metformin users was also lower than in the other two groups (OR: 0.828, 95% CI:0.781,0.785). Summary: This comprehensive review showed that the risk of ACM, death due to CVD, and incidents of CVD in DM who use metformin was lower than the patients who received a placebo only or other diabetic drugs, which can guide clinicians in medical decision-making. [ABSTRACT FROM AUTHOR]

Simple Summary: Diabetes affects patients with breast cancer. Women with diabetes and the comorbidities related to diabetes tend to receive less aggressive breast cancer treatments primarily because of the potential side effects of the treatment. Managing proper antidiabetic treatment should affect the patient's breast cancer prognosis in patients with both conditions. This review explores the link between diabetes and an elevated risk of breast cancer, highlighting the global prevalence of these conditions. It delves into the impact of antihyperglycemic therapy, including insulin, metformin, and novel groups: incretins and SGLT-2 inhibitors, on the prognosis of breast cancer in diabetic patients. The review also underscores the increased incidence and mortality rates of breast cancer in individuals with diabetes, along with the role of obesity and its connection to the metastasis process in those undergoing antidiabetic treatment. The role of obesity as a confounding variable is confirmed, highlighting the importance of considering obesity during hypoglycemic therapy selection in breast cancer patients. Diabetes is one of the leading chronic conditions worldwide, and breast cancer is the most prevalent cancer in women worldwide. The linkage between diabetes and its ability to increase the risk of breast cancer should always be analyzed in patients. This review focuses on the impact of antihyperglycemic therapy in breast cancer patients. Patients with diabetes have a higher risk of developing cancer than the general population. Moreover, diabetes patients have a higher incidence and mortality of breast cancer. In this review, we describe the influence of antidiabetic drugs from insulin and metformin to the current and emerging therapies, incretins and SGLT-2 inhibitors, on breast cancer prognosis. We also emphasize the role of obesity and the metastasis process in breast cancer patients who are treated with antidiabetic drugs. [ABSTRACT FROM AUTHOR]

Background: Assessing a patient with Type 2 Diabetes (T2DM) involves a comprehensive evaluation of their medical history, current symptoms, physical examination, and laboratory tests. Here's a structured approach to assessing a patient with T2DM. Evaluate the patient's current diabetes management plan, including diet, exercise, medication adherence, self-monitoring of blood glucose, and insulin administration if applicable. Assess barriers to effective diabetes management, such as socioeconomic factors, access to healthcare, health literacy, and psychosocial support. Collaborate with the patient to set individualized goals for glycemic control, blood pressure, lipid levels, weight management, and prevention of diabetes-related complications. Materials and methods: A six-month longitudinal study was conducted at a tertiary care facility. Those with type 2 diabetes who were receiving insulin and oral hypoglycemics were included in the trial. Laboratory investigations and a sociodemographic profile were gathered using a pretested, structured questionnaire. EPI Info, Open EPI, and SPSS 22 version software were used for the statistical analysis. The statistical tests were the Students t-test and the Chi-square test. Result: There were ninety-nine diabetic individuals in the oral group. Oral hypoglycemics were 46.8±7.6 years old on average. Our research indicates that type II diabetes can be treated with both monotherapy and combination medications. According to the results of this study, the majority of doctors first prescribed monotherapy (25%) consisting of Metformin, Glipizide, Glimepiride, and Gliclazide to control hyperglycemia. Then came triple treatment (40%) including Metformin + Glimepiride + Pioglitazone and dual therapy (35%) comprising FDC of Metformin + Pioglitazone, Metformin + Glipizide, Metformin + Glimepiride, Metformin + Saxagliptin, and Metformin + Voglibose. Conclusion: The most often given medications in our research were biguanide, metformin, and sulfonylureas, such as glimepiride, glibenclamide, glipizide, and gliclazide. [ABSTRACT FROM AUTHOR]

Objective: Using non-geriatric type 2 diabetic patients with and without diabetic foot ulcers (DFUs), this study investigated the frequency of poor handgrip strength and examined the association between handgrip strength and diabetic foot disorder. Methods: The study comprised a total of 525 patients with type 2 diabetes who visited the endocrinology outpatient clinic between August 2020 and June 2022; 242 of them had DFUs. Patients were selected according to inclusion and exclusion criteria. Data on medications used, as well as demographic and clinical information, were taken from hospital archives. The severity of ulcers was assessed using the Wagner score. Using a portable digital dynamometer, a test of handgrip strength was conducted. Low handgrip strength was defined as less than 16 kg for females and 27 kg for males. Results: Patients with DFUs exhibited lower handgrip strength, older age, a longer duration of diabetes diagnosis, a lower body mass index, and higher fasting plasma glucose and hemoglobin A1c levels. Comorbidities such as peripheral artery disease and ischemic heart disease were more frequent in patients with DFUs and low handgrip strength. Diabetic foot ulcer frequency was 3.149 times higher among those with poor hand grip strength than those with good strength (odds ratio = 3.149; 95% CI, 2.118-4.672; P < .001). Conclusion: Non-geriatric type 2 diabetes patients with DFUs had a higher frequency of low handgrip strength. Low handgrip strength was independently associated with the presence of DFUs. This study emphasizes the importance of addressing low handgrip strength as a potential risk factor in managing diabetic foot disease in non-geriatric type 2 diabetic patients. [ABSTRACT FROM AUTHOR]

Ramadan fasting, a religious practice observed by Muslims worldwide, involves abstaining from eating, drinking, smoking, and using oral medications from dawn to dusk during the ninth lunar month. Studies have demonstrated that fasting during Ramadan has been shown to increase HDL cholesterol, leptin, adiponectin, and insulin sensitivity, as well as lower several hemostatic risk factors for cardiovascular diseases. Additionally, it may result in a drop in blood sugar levels, especially in diabetics who are also on blood sugar-lowering medicine. Hypoglycemia, characterized by low blood sugar levels, could also result from fasting during Ramadan. The GLP-1 (glucagon-like peptide-1) hormone plays a significant role in regulating glucose metabolism and insulin secretion, and Ramadan fasting can affect its production and release in the gut. Research contributes to our understanding of the utilization of GL-1 medications during Ramadan among patients, broadening therapy alternatives and offering insightful information for well-informed decision-making. Therefore, this narrative review aims to explore the current evidence that studies the safety and efficacy of GLP-1 agonists during Ramadan for nondiabetic and diabetic patients to ensure healthy fasting during Ramadan. [ABSTRACT FROM AUTHOR]

Sulfonylureas (SU) continue to be a vital therapeutic category of oral hypoglycemic agents (OHAs) for the management of type 2 diabetes mellitus (T2DM). Physicians consider modern SU (gliclazide and glimepiride) as "safe and smart" choices for T2DM management. The presence of multiple international guidelines and scarcity of a national guideline may contribute to the challenges faced by few physicians in choosing the right therapeutic strategy. The role of SU in diabetes management is explicit, and the present consensus aims to emphasize the benefits and reposition SU in India. This pragmatic, practical approach aims to define expert recommendations for the physicians to improve caregivers' knowledge of the management of T2DM, leading to superior patient outcomes. [ABSTRACT FROM AUTHOR]

Background and purpose: Multidrug and toxin extrusion transporter 1 (MATE1), encoded by the SLC47A1 gene and single nucleotide polymorphisms of organic cation transport 1, may impact metformin's responsiveness and side effects. Inward-rectifier potassium channel 6.2 (Kir 6.2) subunits encoded by KCNJ11 may affect the response to sulfonylurea. This study aimed to evaluate the association between SLC22A1 rs72552763 and rs628031, SLC47A1 rs2289669 and KCNJ11 rs5219 genetic variations with sulfonylurea and metformin combination therapy efficacy and safety in Egyptian type 2 diabetes mellitus patients. Experimental approach: This study was conducted on 100 cases taking at least one year of sulfonylurea and metformin combination therapy. Patients were genotyped via the polymerase chain reaction-restriction fragment length polymorphism technique. Then, according to their glycated hemoglobin level, cases were subdivided into non-responders or responders. Depending on metformin-induced gastrointestinal tract side effects incidence, patients are classified as tolerant or intolerant. Findings/Results: KCNJ11 rs5219 heterozygous and homozygous mutant genotypes, SLC47A1 rs2289669 heterozygous and homozygous mutant genotypes (AA and AG), and mutant alleles of both polymorphisms were significantly related with increased response to combined therapy. Individuals with the SLC22A1 (rs72552763) GAT/del genotype and the SLC22A1 (rs628031) AG and AA genotypes were at a higher risk for metformin-induced gastrointestinal tract adverse effects. Conclusion and implications: The results implied a role for SLC47A1 rs2289669 and KCNJ11 rs5219 in the responsiveness to combined therapy. SLC22A1 (rs628031) and (rs72552763) polymorphisms may be associated with increased metformin adverse effects in type 2 diabetes mellitus patients. [ABSTRACT FROM AUTHOR]

Background and aims: The present study aimed to compare the levels of the inflammatory biomarkers of fibrinogen and highsensitivity C-reactive protein (hs-CRP) among type 2 diabetic patients treated with empagliflozin and other hypoglycemic drugs. Methods: This cross-sectional study was performed on 90 patients with type 2 diabetes (≥30 years) receiving empagliflozin, metformin, and sulfonylurea who were referred to the diabetes clinics affiliated with Arak University of Medical Sciences. After obtaining consent to participate in the study, the patients were categorized into the treatment groups of metformin, metformin+empagliflozin, or metformin+sulfonylurea, and their characteristics and hypoglycemic drugs were recorded in the information checklist. The data were analyzed in SPSS 16 statistical software. Results: The fibrinogen level was minimized in the metformin+empagliflozin group, although the three groups were not significantly different in this regard (P=0.382). Based on the results, the parameter was higher in the individuals with ischemic heart disease, while a lower level was found among those treated with a lipid-lowering agent. In terms of hs-CRP level, no statistically significant difference was observed among the three groups, although the metformin group had a lower level (P=0.522). Conclusion: The minimum fibrinogen and hs-CRP levels were related to the metformin+empagliflozin and metformin groups, respectively. Further, several factors such as comorbidities and other consumed drugs could affect the concentration of inflammatory factors. Thus, it is suggested that clinical trials should be conducted in this respect. [ABSTRACT FROM AUTHOR]

AimsType 2 diabetes mellitus (T2DM) is a strong risk factor for complications of coronavirus disease 2019 (COVID-19). The effect of T2DM medications on COVID-19 outcomes remains unclear. In a retrospective analysis of a cohort of 131 patients with T2DM hospitalized for COVID-19 in Wuhan, we have previously found that metformin use prior to hospitalization is associated with reduced mortality. The current study aims to investigate the effects of inpatient use of T2DM medications, including metformin, acarbose, insulin and sulfonylureas, on the mortality of COVID-19 patients with T2DM during hospitalization.MethodsWe continue to carry out a retrospective analysis of a cohort of 131 patients with T2DM hospitalized for COVID-19 and treated with different combinations of diabetes medications.ResultsWe found that patients using metformin (p = .02) and acarbose (p = .04), alone or both together (p = .03), after admission were significantly more likely to survive than those who did not use either metformin or acarbose. 37 patients continued to take metformin after admission and 35 (94.6%) survived. Among the 57 patients who used acarbose after admission, 52 survived (91.2%). A total of 20 patients used both metformin and acarbose, while 57 used neither. Of the 20 dual-use patients, 19 (95.0%) survived.ConclusionOur analyses suggest that inpatient use of metformin and acarbose together or alone during hospitalization should be studied in randomized trials.

To investigate the effect of an academic detailing intervention on the utilisation of type 2 diabetes medication among general practitioners. We developed an academic detailing campaign based on the revised national treatment guideline for diabetes and the best available evidence. General practitioners were offered a 20-minute one-to-one visit by a trained academic detailer. A total of 371 general practitioners received a visit and represented the intervention group. The control group consisted of 1282 general practitioners not receiving a visit. Changes in prescribing from 12 months before to 12 months after the intervention. The primary endpoint was a change in metformin. Secondary endpoints were changes in other groups of Type 2 diabetes medication and of these drugs in total. Prescribing of metformin increased by 7.4% in the intervention group and 5.2% in the control group (p =.043). Sodium-glucose cotransporter-2 inhibitors increased by 27.6% in the intervention group and 33.8% in the control group (p =.019). For sulfonylureas there was a decrease of 3.6% in the intervention group vs. 8.9% in the control group (p =.026). The total amount of prescribed medications for type 2 diabetes increased by 9.1% in the intervention group and 7.3% in the control group (p =.08). Academic detailing initiated a small but statistically significant increase in the prescription of metformin. For a complex subject like type 2 diabetes, we recommend reserving more time in the visit than the 20 min our campaign aimed for. Academic detailing is a validated method for facilitating changes in prescribing, via interactive one-to-one meetings with a trained academic detailer. General practitioners who received a 20-minute visit on the treatment of type 2 diabetes prescribed more metformin, compared to the control group. For a complex interventions like the present, we recommend setting aside more than 20 minutes, to ensure sufficient time for discussion and reflection. Academic detailing can impact prescribing, even for a complex subject like the treatment of Type 2 Diabetes. [ABSTRACT FROM AUTHOR]

Aims: The aim of our meta‐analyses was to compare the effects of glucose‐lowering drugs on mortality, cardiovascular and renal endpoints for a range of type 2 diabetes (T2D) subgroups defined by their specific cardiovascular risk profile. Methods: Meta‐analyses comparing drugs within the classes of GLP‐1RAs and SGLT‐2 inhibitors were performed and compared to sulphonylureas and DPP‐4 inhibitors with available cardiovascular outcome trials. The comparison between the different classes of glucose‐lowering drugs included analyses of T2D populations with low risk and high risk for cardiovascular disease including populations with established cardiovascular disease and/or kidney disease. Outcomes included mortality, major cardiovascular adverse events (MACE), hospitalisation for heart failure (HHF) and a composite renal endpoint as applied in the underlying clinical trials. Results: SGLT‐2 inhibitors and GLP‐1RAs showed beneficial effects on mortality and MACE compared to the classes of DPP‐4 inhibitors and sulphonylureas. SGLT‐2 inhibitors were shown to be the most effective treatment in terms of HHF and kidney disease. Metformin was used as background therapy for the vast majority of participants in all included studies. Overall, the absolute effects of SGLT‐2 inhibitors and GLP‐1RAs on these important outcomes were evident for patients with established or at high risk for cardiovascular disease but limited for the low‐risk subgroup. Conclusions: The findings from our analyses substantiate the relevance of treatment with SGLT‐2 inhibitors or GLP‐1RAs as an add‐on to metformin in patients with T2D and a high risk for cardiovascular disease, and furthermore, support the recommendation for SGLT‐2 inhibitor treatment in patients with T2D and heart failure or established kidney disease. [ABSTRACT FROM AUTHOR]

Background and aims: Hypoglycemic agents are the primary therapeutic approach for the treatment of diabetes and have been postulated to impact pancreatic cancer (PC) incidence in diabetic patients. We conducted a metaanalysis to further evaluate and establish the associations between four common types of hypoglycemic agents [metformin, sulfonylureas, thiazolidinediones (TZDs), and insulin] and PC incidence in individuals with diabetes mellitus (DM). Methods: A comprehensive literature search of PubMed, Web of Science, Embase, and the Cochrane Library identified studies that analyzed the relationship between hypoglycemic agents and PC published between January 2012 and September 2022. Randomized control trials (RCTs), cohorts, and case-control studies were included if there was clear and evaluated defined exposure to the involved hypoglycemic agents and reported PC outcomes in patients with DM. Furthermore, reported relative risks or odds ratios (ORs) or other provided data were required for the calculation of odds ratios. Summary odds ratio estimates with a 95% confidence interval (CI) were estimated using the random-effects model. Additionally, subgroup analysis was performed to figure out the source of heterogeneity. Sensitivity analysis and publication bias detection were also performed. Results: A total of 11 studies were identified that evaluated one or more of the hypoglycemic agents, including three case-control studies and eight cohort studies. Among these, nine focused on metformin, six on sulfonylureas, seven on TZDs, and seven on insulin. Meta-analysis of the 11 observational studies reported no significant association between metformin (OR = 1.04, 95% CI 0.73-1.46) or TZDs (OR = 1.13, 95% CI 0.73-1.75) and PC incidence, while the risk of PC increased by 79% and 185% with sulfonylureas (OR = 1.79, 95% CI 1.29-2.49) and insulin (OR = 2.85, 95% CI 1.75-4.64), respectively. Considerable heterogeneity was observed among the studies and could not be fully accounted for by study design, region, or adjustment for other hypoglycemic agents. Conclusion: Sulfonylureas and insulin may increase the incidence of pancreatic cancer in diabetic patients, with varying effects observed among different ethnicities (Asian and Western). Due to significant heterogeneity across studies, further interpretation of the relationship between hypoglycemic agents and pancreatic cancer incidence in diabetic patients requires well-adjusted data and better-organized clinical trials. [ABSTRACT FROM AUTHOR]

Due to its prevalence and socio-economic burden on health systems, diabetes mellitus (DM) is considered a major health emergency. This retrospective, observational study aimed to describe a population of DM-naïve patients of the Local Health Authority (LHA) ASL TO4 Regione Piemonte and the prescriptive behavior of LHA general practitioners. Drug dispensing data collected between January 2018 and December 2021 was analyzed. Adult patients were included if they received their first prescription for an antidiabetic drug (AD) in 2019 and had ≥2 prescriptions/year of ADs during the follow-up. Patients who started antidiabetic therapy with metformin were selected to investigate comorbidities, medication adherence, and first treatment intensification. Comorbidities were identified through a modified version of the Rx-Risk Index; adherence was measured as the continuous measure of medication availability (CMA). Among 1927 DM-naïve patients, 1361 started therapy with metformin. Most of them received drugs related to cardiovascular diseases, hypertension, and infectious diseases during the study period. Median CMA was 58.8%, with the majority of patients being partially adherent to ADs (40 ≤ CMA < 80). Initial antidiabetic therapy was mostly modified (switch, add-on) with SGLT-2 inhibitors and sulfonylureas. These findings help to identify areas of intervention to improve the use of ADs in the LHA. [ABSTRACT FROM AUTHOR]

Background: Hip fracture is a major health problem that occurs more often in the elderly, especially in diabetic patients. Some studies have been conducted regarding the effect of anti- diabetic drugs on fractures. But so far, no meta-analysis study has been conducted to investigate the effect of diabetic drugs on hip fractures. Therefore, this study investigated the relationship between anti-diabetic drugs (Metformin, Sulfonylurea, and insulin) with hip fractures. Methods: In this systematic review and meta analysis study, PubMed, Scopus, Google Scholar, and Web of Science databases were searched with specific keywords to find relevant studies. Two researchers included related studies after screening based on the title and full text. Cochran's Q and I2 tests were used to assess heterogeneity between studies. Publication bias between studies was evaluated for each drug using Egger's test. A 95% confidence interval was used for effect size significance. Overall, 49 studies, including 6,631,297 participants, were reviewed. Results: The results showed that metformin significantly reduced the risk of hip fracture (HR: 0.833, 95% CI: 0.759, 0.914, P:0.001). Consumption of sulfonylurea compounds was significantly associated with an increased risk of hip fracture. (HR: 1.175, 95% CI:1.068,1.293, P:0.001), The risk of hip fracture in patients receiving insulin was significantly higher than in diabetic patients who did not receive insulin. (HR:1.366, 95% CI:1.226,1.522, P:0.001). Conclusion: The results of this study showed that taking metformin reduces the risk of hip fracture, and insulin and Sulfonylurea increase the risk of hip fracture. [ABSTRACT FROM AUTHOR]

Adults with obesity may develop asthma that is ineffectively controlled by inhaled corticosteroids and long-acting beta-adrenoceptor agonists. Mechanistic and translational studies suggest that metabolic dysregulation that occurs with obesity, particularly hyperglycemia and insulin resistance, contributes to altered immune cell function and low-grade systemic inflammation. Importantly, in these cases, the same proinflammatory cytokines believed to contribute to insulin resistance may also be responsible for airway remodeling and hyperresponsiveness. In the past decade, new research has emerged assessing whether hypoglycemic therapies impact comorbid asthma as reflected by the incidence of asthma, asthma-related emergency department visits, asthma-related hospitalizations, and asthma-related exacerbations. The purpose of this review article is to discuss the mechanism of action, preclinical data, and existing clinical studies regarding the efficacy and safety of hypoglycemic therapies for adults with obesity and comorbid asthma. [ABSTRACT FROM AUTHOR]

Young maturity-onset diabetes of the young type3(MODY3) as a special type of diabetes, the probability of diagnosis is low. This article reports on a case and reviews the relevant knowledge of the disease. We report an 11-year-and-11-month-old girl whose grandmother died from diabetic complications while the rest of the families were non-diabetes. The proband was initially treated with insulin and metformin but the threatment proved inefficient. After an exome-targeted capture sequencing test, she was diagnosed with mature-onset diabetes of young type 3 (MODY3), and sulfonylureas make sense. The key to mody treatment is a correct and timely diagnosis, which contributes to helping patients overcome the problems of MODY3, especially for blood sugar control. [ABSTRACT FROM AUTHOR]