An endoscopically placed duodenal-jejunal bypass liner (DJBL) may provide a safe adjunctive therapy for those with poorly controlled type 2 diabetes mellitus (T2DM) and obesity. Although some endoscopic therapies have been shown to improve glycemic indices secondary to weight loss, small bowel interventions may have direct metabolic effects. A meta-analysis of observational studies demonstrated reduction in HbA1c by 1.3% at 1 year after DJBL in patients with T2DM and obesity. This was a multicenter, double-blind, randomized, sham-controlled trial comparing DJBL to sham procedure with medical management and lifestyle modification. Primary endpoints included mean difference in changes in HbA1c at 12 months between arms, and device-related serious adverse events (SAEs). Secondary endpoints included percent total weight loss (%TWL) and subjects achieving HbA1c≤7% and TWL≥5% at 12 months. Three hundred twenty subjects were randomized to DJBL (n=212) and sham (n=108). Baseline HbA1c and BMI were 8.79±0.92% and 38.45±5.75kg/m 2 . On modified intent-to-treat analysis, change in HbA1c at 12 months was -1.10±1.45% and -0.28±1.54% for DJBL and sham groups, respectively ( P =0.0004). Rate of device-related SAEs was 9.4% including intolerance (3.7%), hemorrhage (2.8%), and hepatic abscess (2.3% stopping study early). At 12 months, DJBL group experienced greater weight loss compared with sham (7.7±9.6% TWL and 2.1±5.4% TWL, respectively; P <0.0001), with significantly more patients achieving HbA1c ≤ 7% (28.3% vs. 9.4%; P <0.0003) and TWL ≥ 5% (60.4% vs. 21.3%; P <0.0001). DJBL met primary glycemic control efficacy and primary safety endpoints, while providing clinically significant weight loss, and comorbidity improvement.

To evaluate the efficacy, safety and immunogenicity of semaglutide injection (synthetic) (Test group) compared with the Reference semaglutide injection [Ozempic, (Reference group)] in Indian patients with Type 2 diabetes mellitus (T2DM). This Phase III, randomised, open-label, multi-centre, parallel-group, active-controlled non-inferiority study was conducted across 35 centres in India. Adults aged 18-65 years with T2DM and baseline glycated haemoglobin (HbA1c) ≥ 7.0% to ≤ 10.5% despite stable metformin therapy and diet & exercise control were randomised (1:1) to receive subcutaneous injections of Test semaglutide or Reference semaglutide once weekly for 24 weeks, using an identical dose-escalation regimen (from 0.25 to 2.0 mg per week). The primary endpoint was change in HbA1c from baseline to Week 24. Secondary endpoints included changes in fasting and post-prandial blood glucose, bodyweight and HbA1c < 7.0% achievers, safety and immunogenicity. A total of 314 patients were randomised, and 290 patients completed the study. At Week 24, both treatments produced significant and comparable reductions in HbA1c (Test: -2.04%, Reference: -1.95%; p < 0.0001 within groups). The least-squares mean difference (Test-Reference) was -0.09% (95% CI: -0.26 to 0.09), meeting the pre-specified non-inferiority criterion. Improvements in fasting and post-prandial blood glucose, patients achieving HbA1c < 7.0% and bodyweight were similar between the two groups. The most common treatment-emergent adverse events were predominantly mild-to-moderate gastrointestinal events (Test vs. Reference: 43.3% vs. 46.5%). No anti-drug or neutralising antibodies were detected. The Test synthetic semaglutide injection demonstrated non-inferior glycaemic efficacy, comparable safety in comparison to Reference semaglutide, supporting its use as an effective therapeutic option for patients with T2DM. Prospectively registered on the Clinical Trials Registry-India, CTRI/2025/02/080592 [Registered on: 14/02/2025], URL: https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MTIwODUw&Enc=&userName=.

To compare the efficacy and safety of the fixed-ratio combination of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) with premixed insulin degludec plus insulin aspart (IDegAsp) according to the injection time of IDegAsp. The 24-week, multicentre, randomised, open-label Soli-D study enrolled Chinese adults with type 2 diabetes (T2D) suboptimally controlled with oral antidiabetic drugs (OADs). This exploratory analysis evaluated glycaemic efficacy, body weight, basal insulin daily dose and hypoglycaemia outcomes with once-daily iGlarLixi (injected before breakfast) versus IDegAsp (injected before breakfast, lunch or dinner). Of 582 participants, 291 received iGlarLixi, with injections self-administered before breakfast, and 291 received IDegAsp, with injections self-administered before breakfast (n = 139), lunch (n = 54) or dinner (n = 98). Glycated haemoglobin (HbA1c) reductions from baseline to Week 24 were greater with iGlarLixi than IDegAsp injected before lunch (least squares mean difference -0.24% [-2.3 mmol/mol]) or dinner (-0.29% [-3.2 mmol/mol]), and slightly greater than IDegAsp injected before breakfast (-0.12% [-1.3 mmol/mol]). Average 2-h postprandial glucose (2-h PPG) reductions were also greater with iGlarLixi than IDegAsp, regardless of injection time. iGlarLixi provided additional benefits, including reduced body weight, lower total insulin doses and less hypoglycaemia risk compared with IDegAsp in all injection-time subgroups. Once-daily iGlarLixi, injected before breakfast, was associated with improved HbA1c control and greater average 2-h PPG reductions compared with IDegAsp, regardless of injection time, in Chinese adults with T2D suboptimally controlled with OADs.

Efficacy and safety of novel formulation of semaglutide injection: A multicentre, randomized, comparative, active controlled, phase 3 study in comparison with reference biologic in Indian patients with type 2 diabetes mellitus

Background: Algorithm-based insulin dosing systems are increasingly used in hospitals and have shown the potential to efficiently and safely enable glycemic control. The goal of this study was to evaluate glycemic control using the ultralong-acting basal insulin degludec (IDeg) in combination with insulin aspart (IAsp) within an algorithm-driven electronic clinical decision support system (cDSS) in inpatients with type 2 diabetes (T2D). Methods: In this non-controlled single-arm pilot study, an electronic, algorithm-based cDSS was applied for the management of insulin treatment in an internal general ward. Thirty hospitalized patients with T2D (18 female, age 74.1 ± 10.9 years, HbA1c 72.4 ± 22.3 mmol/mol, BMI 28.6 ± 5.6 kg/m2, diabetes duration 13.2 ± 11.6 years, creatinine 1.5 ± 1.2 mg/dL, length of hospital stay 9.1 ± 4.0 days) were included in the study. Capillary blood glucose (BG) was evaluated four times daily using a point-of-care device integrated into the hospital information system. In addition, all participants received a blinded continuous glucose monitoring (CGM; Abbott Freestyle Libre Pro) system. The primary endpoint was defined as the percentage of BG measurements within the target range of 3.9–7.8 mmol/L. Results: Overall, 722 BG values and 17,242 CGM data points were available. Of those, 52.2% and 55.0% were in the specified target area (3.9–7.8 mmol/L), respectively. Mean BG prior to study start was 11.9 ± 4.4 mmol/L and improved to 7.5 ± 1.9 mmol/L and 7.4 ± 1.4 mmol/L after 6 and 10 days of treatment. BG < 3.9, <3.0 and <2.2 mmol/L was 1.25%, 0.28% and 0%, respectively. Adherence to the total daily insulin dose suggested by the cDSS was 94.2%, and 99.5% of all basal and 85.3% of all bolus insulin suggestions were accepted by the nurses in charge. Basal-bolus therapy using the cDSS covered 85% of the participants’ total hospital stay. Conclusions: Glycemic control using IDeg within an algorithm-driven cDSS could effectively and safely be achieved in the hospital and was highly accepted.

Design of potent, proteolytically stable stapled lipopeptide analogues of BimBH3 as PTP1B inhibitors for diabetes therapy.

Background: Tirzepatide, a dual GIP/GLP-1 receptor agonist, demonstrates substantial glycemic and weight benefits versus GLP-1 receptor agonists in indirect comparisons, but direct comparative safety evidence versus dulaglutide remains limited. We evaluated comparative safety (primary outcome: overall adverse events) and efficacy. Methods: Following PRISMA 2020 (prospectively registered: PROSPERO CRD420251276594), we searched MEDLINE, Embase, Scopus, and CENTRAL (inception-31 December 2025) for randomized controlled trials (≥26 weeks) comparing once-weekly tirzepatide with dulaglutide in adults with type 2 diabetes. Three trials (N = 13,590 participants) were included. Dichotomous outcomes were pooled using random-effects models (risk ratios [RRs], 95% confidence intervals [CIs]). GRADE assessed certainty of evidence. Results: Overall adverse event incidence did not differ significantly (RR 1.04 [0.98-1.10]; I2 = 36%; moderate-certainty evidence). Discontinuation due to adverse events was consistently higher with tirzepatide (RR 1.32 [1.20-1.45]; I2 = 0%; high-certainty evidence), representing a 32% increased risk across all populations. Categorical HbA1c target achievement was analyzed in two trials; the third trial reported HbA1c as a continuous outcome only. At the primary threshold (HbA1c < 7.0%), tirzepatide was consistently superior with no heterogeneity (RR 1.48 [1.33-1.64]; I2 = 0%; p < 0.00001). Across all thresholds combined, heterogeneity was extreme (I2 = 92%), limiting confidence in any pooled summary estimate; the greatest instability occurred at the strictest threshold (HbA1c < 5.7%; I2 = 98%; p = 0.40). Tirzepatide showed greater HbA1c target attainment in treatment-naive patients receiving dulaglutide 0.75 mg, whereas the glycemic advantage was smaller in patients with established cardiovascular disease receiving dulaglutide 1.5 mg. Categorical weight-loss outcomes were analyzed in two trials; tirzepatide was associated with greater weight-loss threshold achievement (RR 8.80 [4.04-19.17]; very low-certainty evidence), although interpretation is limited by substantial heterogeneity and restricted generalizability. Serious adverse events were not significantly different (RR 0.82 [0.47-1.43]; I2 = 42%). Conclusions: Overall adverse events were similar between treatments, but tirzepatide consistently increased discontinuation risk, indicating a clinically important tolerability-persistence trade-off. Glycemic efficacy was highly population-dependent: benefits were consistent at the primary HbA1c target (<7.0%; I2 = 0%) in early-stage disease, whereas the advantage was smaller in long-standing disease with established cardiovascular disease. Tirzepatide may be favored when glycemic or weight efficacy is prioritized in earlier-stage disease, provided tolerability is proactively managed. Dulaglutide remains appropriate when persistence is threatened by tolerability concerns or cardiovascular risk reduction is the primary goal.

Background:Type 2 diabetes mellitus (T2DM) is associated with microvascular and macrovascular complications, contributing substantially to the global disease burden. This study aimed to evaluate the real-world safety, efficacy,and prescribing patterns of dapagliflozin in T2DM managementto support tailored diabetes care. Methods: This questionnaire-based study included a 12-item questionnaire that evaluated physicians' perspectives and prescribing patterns related to dapagliflozin, with a specific focus on their last 10 patients with T2DM. Results: A total of 251 physicians from southern India participated. Nearly half (44.22%) reported initiating dapagliflozin in 3-5 of their last 10 elderly patients (≥65 years). Dapagliflozin was most commonly preferred for patients with CKD (28.69%), followed by those with poor glycemic control or cardiovascular disease (27.49%). Adherence was high with 62.55% noting that 9-10 patients continued therapy for at least six months, cost was the main reason for discontinuation (41.43%). Most physicians (37.45%) reported no major concerns in elderly patients. Among female patients, 0-2 out of 10 experienced urinary tract infections (52.99%). Nearly half (47.01%) felt their patients were very satisfied with dapagliflozin. Cardiovascular protection (33.07%) and glycemic control (29.08%) were the main reasons for prescribing, and metformin was the most common add-on therapy (59.36%). Physicians also reported glycemic efficacy comparable to other sodium-glucose co transporter 2 (SGLT2) inhibitors (42.23%) and cardiovascular benefits comparable to glucagon-like peptide-1(GLP-1) receptor agonists (49.40%). Most (55.38%) expressed a high likelihood of prescribing it in the future. Conclusion: Physicians prefer dapagliflozin as an effective agent for both monotherapy and combination therapy in T2DM management.

Diabetes mellitus is a chronic disease requiring multifunctional natural agents. Arctium lappa is traditionally used in Eastern and European medicine to address metabolic disorders. This comprehensive narrative review, conducted between 2000 and 2025 using international databases (Scopus, PubMed, Web of Science Core Collection, and Google Scholar), evaluates the species through its ethnomedicine, phytochemistry, preclinical evidence, and safety. The available evidence suggests that A. lappa exerts antidiabetic effects via multi-layered mechanisms, including AMPK activation, insulin signaling modulation, and increased GLUT4 translocation. Key bioactives (arctigenin, arctiin, and inulin) collectively improve insulin sensitivity and lipid metabolism. However, preclinical studies confirm these effects in animal models, while limited clinical data in non-diabetic cohorts focus on systemic inflammation. This highlights a significant gap in randomized controlled trials targeting glycemic control in diabetic populations. In this context, while A. lappa shows promise as a potential metabolic regulator; this evidence is currently derived primarily from in vitro and animal models. Systematic clinical trials are urgently required to establish glycemic efficacy in humans, validate its therapeutic potential, and determine the optimal dosage and safety profile. This review evaluates the multi-targeted biological potential of A. lappa to guide future research and evidence-based application.

Background: Despite metformin being the established first-line pharmacotherapy for type 2 diabetes mellitus, many patients require additional antidiabetic agents to achieve glycemic targets. The comparative effectiveness of second-line oral antidiabetic drug classes in real-world clinical settings requires further evaluation. Methods: A prospective observational study was conducted involving 180 patients with inadequately controlled type 2 diabetes on metformin monotherapy, who were prescribed either sulfonylurea (n=60), DPP-4 inhibitor (n=60), or SGLT-2 inhibitor (n=60) as add-on therapy. Glycemic parameters, body weight, and adverse events were assessed at baseline and after 24 weeks of treatment. Results: All three drug classes significantly reduced HbA1c from baseline. The SGLT-2 inhibitor group demonstrated the greatest HbA1c reduction (-1.18 ± 0.42%), followed by sulfonylurea (-1.08 ± 0.48%) and DPP-4 inhibitor (-0.86 ± 0.38%) groups (p=0.001). Significant weight reduction occurred with SGLT-2 inhibitors (-2.84 ± 1.42 kg; p&lt;0.001), while weight gain was observed with sulfonylureas (+1.62 ± 1.18 kg; p&lt;0.001). Hypoglycemia incidence was highest with sulfonylureas (18.3% vs. 3.3% DPP-4 inhibitors vs. 5.0% SGLT-2 inhibitors; p=0.006). Conclusion: SGLT-2 inhibitors and sulfonylureas provide superior glycemic efficacy compared to DPP-4 inhibitors when added to metformin, with SGLT-2 inhibitors offering additional weight reduction benefits and lower hypoglycemia risk.

Current automated insulin delivery (AID) systems recommend manual insulin delivery prior to meals (hybrid closed-loop [HCL]). Data are needed on the efficacy of an AID system without meal announcement. In this randomized, open-label, parallel-arm trial, we established participants with type 1 diabetes aged 18-70 years on an open-source AID system, with meal announcement, during a 12-week run-in phase, followed by a 12-week trial phase with assignment in a 1:1 ratio to AID without meal announcement or HCL (continued meal announcement). The primary outcome was the percentage of time in the target glucose range of 70-180 mg/dL (3.9-10.0 mmol/L) in the final 14 days of the trial phase, adjusted for the same metric in the final 14 days of the run-in phase. In total, 73 participants underwent randomization (36 to AID without meal announcement and 37 to HCL). Mean (±standard deviation) time in the target range at the end of the run-in and trial phases was 69 ± 11% and 66 ± 8% in the AID without meal announcement and 70 ± 9% and 69 ± 13% in the HCL group (adjusted difference, -2.2 percentage points; 95% confidence interval: -6.2 to 1.7). In adults with type 1 diabetes, use of an open-source AID system without meal announcement demonstrated glycemic efficacy and achieved a similar time in the target glucose range to use of the same system as HCL.

Type 2 Diabetes Mellitus is a principal driver of global morbidity, requiring pharmacological interventions that transcend simple glycemic control. While both Sodium-Glucose Cotransporter-2 (SGLT-2) inhibitors and Dipeptidyl Peptidase-4 (DPP-4) inhibitors serve as important components of the modern antihyperglycemic armamentarium, their clinical impacts diverge significantly. SGLT-2 inhibitors facilitate glucose excretion through insulin-independent pathways in the renal proximal tubule, concurrently promoting natriuresis and caloric loss. These physiological changes translate into robust reductions in hospitalization for heart failure, attenuation of chronic kidney disease progression, and decreased cardiovascular mortality. Conversely, DPP-4 inhibitors augment the incretin effect by prolonging the half-life of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, leading to glucose-dependent insulin secretion and suppressed glucagon release. These agents exhibit a high degree of tolerability and weight neutrality but lack the transformative cardio-protective and renoprotective benefits observed with SGLT-2 inhibition. Systematic evaluation of randomized controlled trials and large-scale outcome data confirms that SGLT-2 inhibitors represent the preferred therapeutic choice for patients with established or high-risk cardiovascular and renal complications. DPP-4 inhibitors maintain clinical relevance as safe, second-line options for individuals requiring simplified glycemic management without the need for significant hemodynamic modification. The integration of these two classes in combination therapy offers additive glycemic efficacy without increasing hypoglycemia risk, though the long-term survival advantages remain largely driven by the SGLT-2 inhibitory component. Strategic selection between these classes allows for a personalized approach that addresses both metabolic targets and the overarching risk of organ damage

Insulin has been around for a century since its discovery and has seen multiple innovations to improve its pharmacokinetic profile, thus impacting its efficacy, safety, and patient compliance. Despite its powerful glycemic efficacy, the use of insulin has remained sub-optimal owing mainly to the invasive route of administration and associated barriers. Non-invasive insulin development has been one of the highly researched fields in diabetes management. Amongst the various non-invasive routes investigated for insulin delivery, the pulmonary route has been among the most evaluated ones - a route that has yielded the only existing non-invasive option, inhaled insulin. Technosphere® insulin (Afrezza®; Mannkind Corporation, Danbury, CT, USA) is the only available inhaled insulin that has regulatory approval for the treatment of adult individuals with diabetes mellitus and has been available for more than a decade. This review article provides an overview of the pulmonary route of administration and charts the developmental journey of inhaled insulins, with a focus on Technosphere® insulin.

This review briefly summarizes imeglimin’s discovery, development, properties, mechanisms, and core findings on efficacy and safety from major studies. Imeglimin is a first-in-class, orally available tetrahydro-triazine that was designed from the metformin scaffold to address the pathophysiological defects of β-cell dysfunction and insulin resistance in type 2 diabetes mellitus (T2DM). Pre-clinical work shows that imeglimin partially inhibits mitochondrial complex I, corrects complex III deficiency, lowers reactive oxygen species, and boosts NAD+-dependent ATP generation. This enhances glucose-stimulated insulin secretion and preserves β-cell mass. Additionally, the compound augments endogenous glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) release and improves hepatic and skeletal-muscle insulin signaling, resulting in combined insulinotropic and insulin-sensitizing actions. Pharmacokinetic studies reveal rapid absorption, an elimination half-life of approximately 9–12 h, high oral bioavailability, and predominantly renal excretion with no clinically meaningful interactions with metformin or sitagliptin. In phase 2 and 3 trials, the optimized regimen of 1,000 mg twice daily consistently lowers glycated hemoglobin (HbA1c) by approximately 0.8–0.9% as monotherapy and provides additional reductions of 0.4–0.6% when combined with metformin or insulin. It maintains placebo-like tolerability and a minimal risk of hypoglycemia. Long-term data confirm durable glycemic efficacy, a neutral cardiovascular profile with no QT/QTc prolongation, and predominantly mild gastrointestinal adverse events. Real-world evidence supports sustained HbA1c lowering, modest weight loss, and lipid improvements over 12 months, independent of age, sex, body mass index, or renal function. Multivariate and cluster analyses suggest that older age, therapy-naive status, and lower baseline HbA1c predict a more pronounced response, highlighting the importance of patient stratification. Research on imeglimin for T2DM is constrained by small sample sizes, mainly Japanese data, lack of cardiovascular outcome trials, limited comparisons with other antidiabetic drugs, and insufficient long-term safety information. More studies are needed to clarify its efficacy and safety profiles.

Tirzepatide, a novel dual GIP/GLP-1 receptor agonist, has demonstrated superior glycemic efficacy in randomized clinical trials. However, real-world data in Indian populations remain limited. The primary objective of this multicenter retrospective study was to evaluate the change in glycated hemoglobin (HbA1c) at 12 weeks (three months) following initiation of tirzepatide in Indian adults with type 2 diabetes mellitus treated in routine clinical practice. Secondary objectives included assessment of changes in body weight, blood pressure, lipid parameters, hepatic fibrosis index (FIB-4), and evaluation of tolerability and treatment persistence during follow-up. This retrospective multicenter study included 71 adults with type 2 diabetes who completed three months of tirzepatide therapy across seven centers in Lucknow, Uttar Pradesh. The primary outcome was the change in HbA1c. Secondary outcomes included body weight, blood pressure, lipid parameters, liver enzymes, FIB-4 index, and evaluation of tolerability and treatment persistence. Mean HbA1c decreased significantly from 8.7 ± 1.4% to 6.9 ± 1.0% (mean change -1.8 ± 1.2%, p<0.001), with 59.2% achieving HbA1c <7% at three months. Mean body weight declined by 4.7 ± 3.2 kg (5.7%, p<0.001). Significant improvements were observed in systolic blood pressure (-5.6 mmHg), total cholesterol (-16.6 mg/dL), LDL-cholesterol (-12.2 mg/dL), HDL-cholesterol (+2.6 mg/dL), triglycerides (-46.4 mg/dL), and liver enzymes (all p<0.001). FIB-4 index decreased from 1.24 ± 0.68 to 1.08 ± 0.54 (p=0.004). Gastrointestinal adverse events occurred in 59.2% of patients, predominantly mild to moderate. The treatment discontinuation rate was 22.2%, mainly due to gastrointestinal intolerance (36%) and financial constraints (32%). In routine clinical practice, tirzepatide was associated with substantial glycemic improvement and meaningful weight loss at 12 weeks, along with favorable changes in cardiometabolic risk factors (blood pressure, lipids, hepatic indices). While the safety profile was consistent with global clinical trial data, real-world treatment persistence was significantly influenced by tolerability and affordability, highlighting important context-specific barriers in the Indian healthcare setting.Cost remains a key barrier to long-term use.

Once-weekly insulin efsitora is a novel basal insulin designed to maintain glycaemic control with fewer injections, potentially improving adherence. Data on its efficacy and safety remain scarce. This systematic review and meta-analysis analysed randomized controlled trials (RCTs) comparing the efficacy and safety of once-weekly efsitora versus once-daily basal insulin in adults with type 2 diabetes mellitus (T2D). PubMed, Embase, and Scopus databases were searched up to July 6, 2025 to identify RCTs comparing once-weekly efsitora with once-daily basal insulin for T2D. Primary outcomes included changes in glycated haemoglobin (HbA1c), changes in fasting plasma glucose, change in total weekly insulin dose, and HbA1c target achievement. Statistical analyses were performed using Review Manager (RevMan) version 5.4, employing a random-effects model to pool mean differences (MDs) and 95% confidence intervals (CIs), with heterogeneity assessed using the I2 statistic. Seven RCTs involving 4170 participants were analysed (2347 on efsitora and 1877 on once-daily insulin). At 26 weeks, HbA1c reduction was similar between groups (mean difference (MD) -0.02%; (-0.11 to 0.08; p = 0.74)). At 52 weeks, efsitora achieved statistically significant greater reduction in HbA1c (MD -0.12%; -0.20 to -0.03; p = 0.009) and was associated with a lower change in total weekly insulin dose (MD -30.55, (-46.48 to -14.52; p = 0.0002)). Time in the target glucose range showed a non-significant numerical increase (MD: 1.72 (95% CI: -0.10 to 3.53; p = 0.06)), while time above range decreased (MD: -2.13 (95% CI: -4.01 to -0.25; p = 0.03)). Hypoglycaemia, serious adverse events, injection-site reactions, and hypersensitivity events were comparable across groups, although a numerically, non-significant increase in major adverse events with efsitora was noted, with an odds ratio of 1.22 (95% CI: 0.97-1.53; p = 0.09). Once-weekly insulin efsitora demonstrated comparable glycaemic efficacy and superiority in reduction of HbA1c and change in total weekly insulin dose at 52 weeks, while maintaining an acceptable safety profile. Longer-term studies and real-world data are warranted to further confirm sustained efficacy, safety, and cost-effectiveness.

Only a few studies have investigated the prevalence and safety of oral quadruple regimens for treating type 2 diabetes (T2D), and evidence regarding combinations that include glucagon-like peptide-1 receptor (GLP-1R) agonists remains limited. A descriptive, retrospective, cross-sectional study was conducted to collect information on the use of four non-insulin drug combinations in patients with T2D over a 12-month period. A total of 1,463 patients with T2D were evaluated during the study period, of whom 13.7% met the inclusion criteria and were enrolled. The mean duration of quadruple therapy was 37.0 ± 23.3 months. Sodium-glucose co-transporter-2 (SGLT2) inhibitors were the most common add-on therapy to a prior triple-drug regimen (32.3%), followed by pioglitazone (30.4%), sulfonylureas (21.9%), and GLP-1R agonists (12.9%). The mean reduction in glycated hemoglobin A1c (A1C) during quadruple therapy was 0.98 ± 0.88% compared to baseline values (p < 0.001), with no significant adverse effects or safety concerns reported. Notably, the addition of GLP-1R agonists as the fourth drug resulted in greater weight loss than any other oral antidiabetic medication. Despite the limitations inherent to a retrospective design, this study demonstrates that quadruple regimens can achieve significant reductions in A1C levels while maintaining a favorable safety profile. In this study, 13.7% of patients with T2D received quadruple non-insulin drug combinations. Larger randomized controlled trials are needed to further evaluate their safety, efficacy, limitations, and potential role in T2D management.

BackgroundTo assess the efficacy and safety of a fixed-dose combination (FDC) of dapagliflozin and pioglitazone versus a loose combination (LC) in Patients with Type 2 Diabetes Mellitus inadequately controlled on earlier metformin containing mono therapy.Materials and methodsThis 12-week PRO-1 study was a randomized, open-label, multicenter phase 3 trial that enrolled 180 Indian adults with T2DM, Glycated Hemoglobin (HbA1c) > 7.5% to 10% inadequately controlled with metformin. The participants received once-daily FDC (dapagliflozin 10 mg/pioglitazone 15 mg) or equivalent LC therapy (1:1 randomization). The primary endpoint was the HbA1c change (non-inferiority margin, 0.3). The secondary endpoints included fasting plasma glucose (FPG), postprandial glucose (PPG), and HbA1c < 7.5%.ResultsAt week 12, the least-squares mean HbA1c reduction was − 1.20% (FDC) versus − 1.02% (LC). A between-group difference of − 0.18% (95% CI: −0.56 to 0.20) demonstrated non-inferiority. FPG decreased by − 8.6 mg/dL (FDC) and − 12.0 mg/dL (LC); PPG decreased by − 28.2 mg/dL and − 29.5 mg/dL, respectively. Target HbA1c < 7.5% was achieved in 52.9% (FDC) versus 54.8% (LC) of patients. (mITT population; p = 0.877). Both regimens were generally well tolerated; adverse events were more frequent with the fixed-dose combination than with the loose combination (8.9% versus 1.1%, p = 0.034), but were mild and self-limiting, with no serious events, hypoglycemia, or treatment discontinuation in either group.ConclusionsThe fixed-dose combination of dapagliflozin and pioglitazone was non inferior to separate administration with respect to glycemic efficacy in Indian adults with inadequately controlled type 2 diabetes mellitus receiving metformin, with a favorable and comparable safety profile.Trial registrationCTRI/2024/09/073221.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13098-026-02086-3.

Dipeptidyl peptidase-4 inhibitors and diabetic retinopathy in type 2 diabetes: A network meta-analysis of randomized clinical trials.

ObjectiveTo evaluate the real-world glycemic efficacy of Insulin Icodec in type 2 diabetes mellitus (T2DM) patients and identify independent risk factors for hypoglycemia.MethodsA retrospective cohort study enrolled 139 T2DM patients treated with Insulin Icodec (May 2024–December 2025). Glycemic efficacy was assessed by changes in HbA1c, fasting blood glucose (FBG), and target attainment rate (HbA1c <7.0%). Univariate analysis and Firth penalized logistic regression (correcting for rare-event bias) were used to identify hypoglycemia risk factors.ResultsAfter 12-week treatment, median HbA1c decreased from 8.6% (IQR:7.5%–9.8%) to 6.9% (IQR:6.2%–7.8%) (Z=-10.246, P<0.001); target attainment rate was 58.3% (95%CI:49.7%– 66.5%). Hypoglycemia occurred in 4 cases (incidence:2.9%). All 4 events were non-severe (Level 1 or 2). Firth penalized logistic regression identified age ≥65 years (OR = 5.83, 95%CI:1.09–31.02, P = 0.040) and combined use of ≥2 oral antidiabetic drugs (OADs) (OR = 6.72, 95%CI:1.21–37.25, P = 0.029) as independent risk factors. No significant changes in liver/kidney function were observed (all P>0.05).ConclusionInsulin Icodec exerts robust glycemic-lowering effects with good short-term safety in T2DM patients. Age ≥65 years and combined use of multiple OADs were identified as potential risk factors for hypoglycemia, although these findings are exploratory given the small number of events.