metformin + sitagliptin (Januvia ER / Janumet ER / Janumet XR)

Real-world outcomes of sitagliptin and sitagliptin/metformin single-pill combination treatment in diverse type 2 diabetes populations (DIVERSITY study).

Janez Andrej A, Bojic Mirjana M, Bozek Tomislav T, Kamenov Zdravko Z et al.

Real-world evidence on dipeptidyl peptidase-4 (DPP-4) inhibitors is limited by selective populations in randomized trials. The international, prospective DIVERSITY study evaluated the effectiveness, safety, and treatment acceptability of sitagliptin and sitagliptin/metformin single-pill combination (SPC) in routine clinical practice across diverse type 2 diabetes (T2D) populations. This non-interventional, multicenter study enrolled adults with T2D eligible for sitagliptin or sitagliptin/metformin SPC and followed them for 6 months with three data captures (baseline, ~3 months, ~6 months). The analysis set comprised 2,603 patients (mean age 64.6y ± 10.6; 53.1% women) meeting all criteria and with ≥152 days between first and third captures. Primary outcomes were absolute changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and post-prandial glucose (PPG) from baseline to 6 months. Secondary outcomes included the proportion achieving HbA1c <7% at 3 and 6 months, changes in body mass index (BMI), and hypoglycemia incidence. Safety was assessed in all treated patients (safety analysis set [SAS], n=2,697). Glycemic control improved over the 6-month observation period. Among patients with paired data, mean HbA1c fell from 7.98% to 6.99% (Δ -0.99%, 95% CI -1.05 to -0.93). Reductions were observed with both regimens: sitagliptin monotherapy (Δ -0.93%, 95% CI -1.01 to -0.85) and sitagliptin/metformin SPC (Δ -1.03%, 95% CI -1.11 to -0.96). FPG decreased by -1.91 mmol/L (95% CI -2.03 to -1.79) and PPG by -2.39 mmol/L (95% CI -2.56 to -2.21). The share of patients with HbA1c <7% rose from 16.9% at baseline to 53.7% at 6 months. BMI changes were small and consistent with weight neutrality (mean -0.61 ± 1.33 kg/m²). Treatment-related symptoms of hypoglycemia were rare (3 cases [0.1%] of all treated patients) and treatment acceptability was high: ≥90% patients and investigators reported satisfaction at 6 months. In routine practice across heterogeneous T2D populations, sitagliptin and sitagliptin/metformin SPC were associated with clinically meaningful improvements in HbA1c, FPG, and PPG over 6 months, with effects consistent with a weight-neutral profile, a low reported incidence of hypoglycemia, and high treatment satisfaction. These findings are consistent with the use of sitagliptin-based regimens, whether used as monotherapy or as add-on therapy, as treatment options in routine real-world care, including in older and multimorbid patients.

Correction to "Evidence of a Protective Effect of Metformin on Abdominal Aortic Aneurysm Risk: Insights from an Observational Study and Mendelian Randomisation Analysis Using Putative Metformin Targets".

Postpartum GLP-1 receptor agonists and SGLT-2 therapies in women with prior gestational diabetes: current evidence and uncertainties.

Vanlaer Yana Y, Van de Cauter Ester E, Embo Nina N, Benhalima Katrien K

Gestational diabetes mellitus (GDM) affects approximately 14% of pregnancies and is associated with adverse pregnancy outcomes and a substantially increased risk of long-term cardiometabolic disease. Although glucose levels often normalise postpartum, women with prior GDM have a ten-fold increased risk of developing type 2 diabetes mellitus (T2DM), particularly when early postpartum prediabetes is present. Current prevention strategies, including lifestyle modification and metformin, have in general shown limited effectiveness in this high-risk population. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve glycaemic control, promote weight loss, and reduce cardiovascular risk in people with T2DM and/or obesity. Given the central role of insulin resistance and weight retention in progression from GDM to T2DM, these therapies represent a promising strategy for postpartum diabetes prevention. However, available evidence in women with prior GDM is limited and largely derived from small, short-term studies not adequately powered to assess sustained diabetes prevention or long-term outcomes. Whether GLP-1 RA therapy should be considered an early preventive strategy in this high risk population remains therefore uncertain. The evidence base is now evolving, with the first large multicentre randomised controlled trial (RCT) with a potent GLP-1 RA in women with early postpartum prediabetes following GDM currently underway. In parallel, sodium-glucose cotransporter 2 (SGLT-2) inhibitors have demonstrated robust cardiovascular and renal benefits in T2DM, independent of glycaemic status, and may offer additional preventive potential. Their insulin-independent mechanism and favourable cardiovascular profile are particularly attractive in women with prior GDM, who face elevated long-term cardiometabolic risk. However, uncertainties persist regarding safety in women of reproductive age, use during lactation, optimal timing, and patient selection, highlighting the gap between therapeutic promise and dedicated postpartum trial data. This Debate examines the emerging role of GLP-1 RA and SGLT-2 inhibitors in preventing T2DM after GDM. Despite their potential, important uncertainties remain regarding long-term efficacy and safety. While these therapies may provide a shift beyond lifestyle intervention and metformin, robust trial data and careful consideration of reproductive factors are required before routine implementation. We discuss how pharmacological prevention strategies could be integrated into postpartum care for this high-risk population.

Associations Between Antidiabetic Pharmacotherapy and Hearing Thresholds in Adult Hearing-Impaired Patients With Type 2 Diabetes.

Martines Francesco F, Salvago Pietro P, Vaccaro Francesca F, Vaccaro Davide D et al.

Type 2 diabetes mellitus (T2DM) has increasingly been identified as a risk factor for sensorineural hearing loss, whereas the association between different antidiabetic therapies and hearing thresholds remains poorly characterized. This retrospective observational study evaluated 240 patients with T2DM and 105 normoglycemic controls who underwent standardized pure-tone audiometry at the Audiology Section of the University of Palermo between February 2025 and January 2026. Hearing thresholds were measured using the pure tone average (PTA-mean) at 0.5, 1, 2, and 4 kHz, corresponding to speech-relevant frequencies. Multivariable analysis of covariance, adjusted for age, sex, body mass index, and smoking status, showed that subjects with T2DM had significantly higher PTA-mean values compared to controls (64.4 ± 17.1 dB vs. 56.4 ± 14.8 dB; p = 0.007), indicating worse hearing thresholds. Among specific antidiabetic treatments, GLP-1RAs, metformin, and pioglitazone were associated with lower PTA-mean values. Furthermore, pharmacological class analysis showed that GLP-1 receptor agonists and biguanides were associated with more favorable hearing thresholds. These findings suggest that antidiabetic pharmacotherapy may show class-specific associations with auditory function, supporting the need for prospective studies to evaluate whether hearing outcomes should be considered in the broader management of diabetes-related comorbidities.