INTRODUCTION:Obesity is highly prevalent in India, creating an urgent need for effective management interventions. The study hypothesizes that synthetic semaglutide has comparable safety and efficacy to the innovator drug when used in obese adults for weight management. METHODS:A phase III multicenter randomized active-controlled non-inferiority trial enrolled adults with obesity across 19 centers in India. Subjects were randomized to the test arm receiving synthetic semaglutide (Alkem Laboratories Limited) or the reference arm administered with innovator semaglutide (Wegovy®, Novo Nordisk) over 24 weeks in a 2:1 ratio. The primary efficacy endpoint was the percentage change in body weight,24 weeks post-intervention. Synthetic semaglutide was established to be non-inferior if the lower bound of the one-sided 97.5% confidence interval for the between-group difference did not exceed 4.5%. RESULTS:Of the 249 randomized participants, 246 (98.8%) completed the study. Mean percentage weight loss after 24 weeks was -14.39 ± 4.17% in the test arm and -14.61 ± 4.36% in the reference arm. The least square-mean difference was 0.15% (-0.93 to 1.24), meeting the predefined non-inferiority criterion. Weight loss >10% was achieved by 86.67% (n=143) in the test arm and 83.95% (n=68) in the reference arm (p = 0.5666), while >15% weight loss occurred in 38.79% (n=64) and 40.74% (n=33), respectively (p = 0.7683). Mean body mass index decreased by -4.93 ± 1.43 kg/m² in the test arm and -5.00 ± 1.50 kg/m² in the reference arm (p = 0.7128). Treatment-emergent adverse events were reported in 55.42% (n=92) of test-arm participants and 54.22% (n=45) of reference-arm participants. CONCLUSIONS:Test semaglutide demonstrated non-inferior efficacy, comparable safety, and similar tolerability to the innovator product.

Abstract Background: Fixed-dose combination (FDC) therapy of dapagliflozin and pioglitazone provides a synergistic mechanism of action, potentially improving glycemic control. This study examined the efficacy, safety, and tolerability of a FDC of pioglitazone and dapagliflozin in individuals with type 2 Diabetes mellitus (T2DM) inadequately managed with metformin. Materials and Methods: This was a phase III, prospective, randomized, open-label, multicenter clinical study. The FDC of dapagliflozin 10 mg + pioglitazone 15 mg tablets (test group) or dapagliflozin 10 mg tablets and pioglitazone 15 mg tablets (reference group) were administered separately to 184 T2DM patients for a 12-week period in a 1:1 ratio. The primary endpoint was the mean change in glycosylated hemoglobin (HbA1c) from baseline to the end of 12 weeks, in both groups. The data were analyzed by using appropriate statistical methods. Results: For the test and reference groups, there was no difference in the mean change in HbA1c values from baseline to end of the study −0.86% versus −0.81%, the mean fasting plasma glucose level −33.44 mg/dl versus −33.78 mg/dl, and in the mean postprandial blood glucose level −50.17 mg/dl versus −53.41 mg/dl, respectively. A total of 35 adverse events were reported, which were mild in severity. Conclusion: The FDC of dapagliflozin 10 mg and pioglitazone 15 mg proved to have the efficacy, safety, and tolerability comparable to concomitant separate pill administration of 10 mg dapagliflozin and 15 mg pioglitazone in T2DM patients inadequately controlled on metformin monotherapy.

Obesity in India is rising rapidly, with higher body fat at lower BMI and younger age compared to Western populations, leading to earlier onset of type 2 diabetes and cardiovascular disease in a resource-constrained health system. Protocols for obesity care therefore need to address region-specific challenges and ensure culturally acceptable, feasible treatment options. The Obesity and Metabolic Surgery Society of India (OSSI) and the Endocrine Society of India (ESI) jointly developed India-specific obesity management protocols using a modified Delphi consensus. A protocol development team generated 73 statements based on literature review and expert experience. Seventy-eight experts (38 OSSI, 40 ESI) participated; 100

Abstract Background This study evaluated the efficacy and safety of generic semaglutide compared with innovator Semaglutide in Indian adults with type 2 diabetes mellitus (T2DM). Methods This Phase 3, multicenter, randomized, active-controlled, non-inferiority trial enrolled 320 adults with T2DM inadequately controlled on metformin. Participants were randomized 1:1 to receive either generic semaglutide (Alkem laboratories Ltd.) or innovator Inj. semaglutide (Novo Nordisk) for 24 weeks in step-wise dose escalation from 0.25 mg/week to 2 mg/week. The primary endpoint was change in HbA1c from baseline to Week 24. Secondary endpoints included changes in fasting and post-prandial glucose, body weight, and proportion of patients achieving HbA1c < 7.0%. Safety assessments included adverse events, hypoglycemia, various laboratory parameters. Results Of 320 participants randomized, 313 completed the study. Baseline demographic and clinical characteristics were comparable between groups. At Week 24, both treatments achieved significant HbA1c reductions (mean − 2.20%), with generic semaglutide demonstrating non-inferiority to the reference. Reductions in body weight, fasting and post-prandial glucose were similar between arms. A total of 86.62% of participants achieved HbA1c < 7.0%. Safety profiles were comparable, with predominantly mild-to-moderate adverse events and no treatment-related serious adverse events. Conclusion Generic semaglutide demonstrated non-inferior efficacy and comparable safety to innovator Semaglutide in Indian adults with T2DM inadequately controlled on metformin, offering an effective and accessible therapeutic option in resource-limited settings.

Aims:To evaluate the efficacy and safety of dapagliflozin plus pioglitazone versus comparators on metabolic control and hepatic steatosis in adults with type 2 diabetes mellitus (T2DM), with or without metabolic dysfunction-associated steatotic liver disease (MASLD). Methods:We conducted a systematic review and meta-analysis of randomized and observational studies in PubMed, Embase, Cochrane Central, Scopus, Web of Science with a search updated through January 2026, following peer review. Eligible studies enrolled adults with T2DM with or without MASLD, receiving dapagliflozin plus pioglitazone in comparison with standard care or monotherapy, or as pooled-arm exploratory estimates. The primary outcome was glycemic control (HbA1c and fasting and postprandial glucose levels). Secondary outcomes included body weight, insulin resistance indices, related liver outcomes (liver fat content, NAFLD activity score [NAS], and steatohepatitis resolution), liver enzymes, non-invasive fibrosis indices, lipid parameters, and safety outcomes. Results:Thirteen studies (n = 1411) met the inclusion criteria. Dapagliflozin-pioglitazone significantly improved glycemic control, with a reduction in HbA1c (mean difference -0.49%; 95% CI -0.64 to -0.34), and Fasting Blood Glucose (-11.96 mg/dL; 95% CI -16.30 to -7.62) and Post-Prandial Glucose (-21.54 mg/dL; 95% CI -30.84 to -12.24). Hepatic outcomes also improved, with reductions in liver fat content (standardized mean difference -0.42; 95% CI -0.61 to -0.22) and NAS (standardized mean difference -0.39; 95% CI -0.56 to -0.22), and higher rates of steatohepatitis resolution (risk ratio 1.48; 95% CI 1.13-1.92). Certainty of evidence was moderate for glycemic and steatosis outcomes and low for histological endpoints. Conclusions:Dapagliflozin-pioglitazone combination therapy was associated with improvements in glycemic control and non-invasive markers of hepatic steatosis in adults with T2DM, with or without MASLD, while maintaining a favorable safety profile. Certainty of evidence was moderate for metabolic and steatosis outcomes and low for histological endpoints. Given the predominance of surrogate hepatic endpoints and limited biopsy-confirmed data, these findings should be interpreted with appropriate caution. Systematic review registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=1117019, identifier CRD420251117019.

Obesity is a global health crisis affecting developing nations, including India. The management of obesity continues to evolve with newer drugs, metabolic and bariatric surgery and endoscopic interventions, requiring family physicians and specialists to adapt their clinical practice accordingly. There is an urgent need for a standardized algorithm to diagnose, stage, and treat obesity. The Endocrine Society of India (ESI) and the Obesity Surgeons Society of India (OSSI) appointed a steering committee to develop an evidence-based algorithm for managing patients with obesity in India. This was put to vote by 80 specialists (38 from OSSI and 42 from ESI) in a physical meeting. A proposed stage-wise algorithm based on Edmonton Obesity Staging System, Asian definition of obesity, and resources in India, received 100

AIM:To evaluate the association of dapagliflozin therapy with changes in hepatic steatosis and non-invasive fibrosis surrogate markers in patients with type 2 diabetes mellitus (T2DM) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) over 12 months. METHODS:This is a pre-specified single-arm analysis from a randomised, open-label, parallel-group trial. Of 54 participants randomised to dapagliflozin 10 mg daily, 50 (92.6%) completed the 12-month follow-up and were included in the per-protocol analysis. Assessments at baseline, 3, 6, and 12 months included transient elastography (CAP and LSM), ultrasonography, and biochemical tests. Primary endpoints were changes in hepatic steatosis (CAP) and non-invasive fibrosis surrogates (LSM). RESULTS:Significant reductions were observed in hepatic steatosis (CAP: 316.7 to 245.7 dB/m; mean change - 71.02 dB/m, 95% CI: -63.4 to - 78.6; p < 0.001) and in liver stiffness as a non-invasive fibrosis surrogate (LSM: 8.59 to 7.28 kPa; mean change - 1.31 kPa, 95% CI: -0.92 to - 1.70; p < 0.001). Improvements were also observed in glycaemic control, body weight, lipid profile, liver enzymes, ultrasonographic steatosis grading, and serum fibrosis markers. Genitourinary infections were the most frequently reported adverse events (32%); no serious adverse events were recorded. CONCLUSIONS:Dapagliflozin was associated with significant improvements in hepatic steatosis, non-invasive fibrosis surrogate markers, metabolic parameters, and liver function in T2DM patients with MASLD over 12 months. These findings provide region-specific evidence for an Indian population and support further controlled investigation. However, these findings should be interpreted in light of the pre-specified single-arm design of this analysis, the open-label methodology, relatively small sample size, and the absence of liver biopsy confirmation.

Background:Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder with a rapidly rising global burden. Present study established the non-inferiority and evaluated the safety of Intas semaglutide (test) compared to Innovator semaglutide (reference) in patients with T2DM inadequately controlled on metformin. Methods:This prospective, randomized, open-label, multicenter phase 3 trial, conducted between July-2025 and February-2026, enrolled adult patients (18-65 years) with T2DM and HbA1c level ≥7%-<10.5% at baseline, who had been on diet, exercise and metformin (≥1500 mg/day). Randomized (1:1) patients received either test or reference product, once weekly from 1 to 24 weeks. Primary endpoint was the change in HbA1c level. Secondary endpoints were the change in fasting blood glucose (FBG) level, post-prandial blood glucose (PPBG) level, bodyweight, body mass index (BMI), and lipid parameters. Safety assessment included monitoring of treatment emerged adverse events (TEAEs). Results:Study analyzed 223 (safety set) and 217 (ITT set) patients. Baseline characteristics were comparable between treatment groups. In the ITT (LOCF) set, at week-24, LSM change in HbA1c was -1.50 vs. -1.65 in test vs. reference group, respectively; LSM difference was 0.16 (95% CI: -0.16 to 0.47, P = 0.3266), confirming non-inferiority of the test product. Other efficacy parameters (FBG and PPBG levels, bodyweight and BMI) were also similarly reduced in the test group. The incidence, severity, and pattern of TEAEs were similar, without new safety signals identified. Conclusion:Intas semaglutide showed non-inferiority to reference semaglutide with comparable efficacy, immunogenicity, and safety which may provide a cost-effective alternative treatment option to Indian patients with T2DM. Clinical trial registration number:CTRI/2025/06/089290.

Endocrine disrupting chemicals (EDCs) are exogenous substances that interfere with hormonal pathways, leading to a broad spectrum of adverse health outcomes across the life course. This white paper by the Endocrine Society of India consolidates global and Indian evidence on EDC exposure, health effects, and regulatory challenges. Major classes of EDCs, including pesticides, industrial pollutants, plastic additives, and heavy metals, affect neurodevelopmental, reproductive, metabolic, musculoskeletal, thyroid and other outcomes, with implications extending to future generations through epigenetic and transgenerational effects. Indian data reveal widespread exposure through food, water, packaging material, and industrial waste, with studies linking EDCs to infertility, polycystic ovary syndrome, obesity and diabetes. Despite growing awareness, India lacks a comprehensive regulatory and surveillance framework for EDCs. This white paper outlines key gaps and provides actionable recommendations: strengthening systematic monitoring, harmonizing regulations, promoting research on emerging chemicals, fostering cross-sector and international collaboration, and empowering healthcare professionals and the public. Adoption of structured regulatory mechanisms modeled on global frameworks, combined with public education and institutional accountability, is essential to mitigate risk. Coordinated national efforts that bridge science, policy and community action are urgently needed to safeguard health and environment for future generations.

McCune- Albright syndrome (MAS) is a rare disorder characterized by postzygotic somatic activation mutation of GNAS, leading to constitutively active Gsα and ligand-independent signaling of the Gs-coupled protein receptor. Polyostotic fibrous dysplasia, café-au-lait macules, and endocrine hyperfunction, commonly gonadotropin-independent precocious puberty (GIPP), are the three clinical hallmarks of this condition. Mosaicism results in a wide range of clinical presentations. In this case series, we present three cases of MAS with varied presentations. Case 1 describes a 9-year-old boy with recurrent fractures and craniofacial fibrous dysplasia. Case 2 is an 8-year-old girl with early menarche and GIPP. Case 3 details a 7-year-old girl with unilateral early breast development progressing from GIPP to gonadotropin-dependent precocious puberty (GDPP). As it is a heterogeneous disorder, it requires individualized management. Prompt recognition of clinical features can aid early diagnosis and intervention to mitigate disease progression.

Introduction: Insulin resistance plays the central role in the pathophysiology of polycystic ovary syndrome (PCOS). While metformin is widely used, its metabolic and androgen-lowering benefits are modest and often limited by tolerability, highlighting the need to evaluate newer therapeutic agents targeting insulin resistance in PCOS. Dapagliflozin complements metformin’s effects through an insulin-independent mechanism of action and may be beneficial in improving metabolic outcomes in PCOS. Methods: Women diagnosed with PCOS based on Rotterdam criteria were randomly allocated to receive either dapagliflozin (10 mg daily) plus metformin (2000 mg/day) or metformin (2000 mg/day) alone, over a 12-week period. Results: At 12 weeks, there were no statistically significant differences between the dapagliflozin plus metformin group and the metformin alone group in improving insulin resistance or biochemical hyperandrogenism. While within-group changes were statistically significant, the differences between the two arms did not achieve statistical significance. Mild adverse effects, including urinary tract infections and vaginal irritation, were reported more in the dapagliflozin plus metformin group than the metformin alone group. Conclusion: In overweight and obese women with PCOS, the addition of dapagliflozin to metformin did not result in significant improvement in insulin resistance or hyperandrogenaemia over metformin alone and was associated with a higher rate of adverse effects. Larger and longer-term trials are needed to fully clarify their role in routine clinical care.

Obesity and type 2 diabetes mellitus (T2DM) are global challenges, with obesity increasing risk of T2DM. Body mass index (BMI), the conventional measure of obesity, may not accurately predict metabolic risk, especially in Asian individuals. Evaluation of alternative anthropometric indices may offer additional approaches for risk assessment. The multicenter, cross-sectional study examined whether anthropometric indices—such as waist, hip, neck, calf, and wrist circumferences, as well as waist–hip, neck–height, and waist–calf ratios—are associated with T2DM in adults with obesity. The study included 750 adults (BMI ≥ 25 kg/m2) recruited from four endocrinology centers across India. Anthropometric and clinical data were recorded using a standardized electronic form. T2DM was present in 73

Background and objectives Liver fibrosis is a key stage in chronic liver disease progression, marked by excessive extracellular matrix (ECM) deposition that disrupts liver architecture. Non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome, is a growing global health concern. This is especially true for individuals with type 2 diabetes mellitus (T2DM). Chronic hyperglycemia in T2DM may accelerate hepatic fibrogenesis. This happens through oxidative stress, inflammation, and impaired lipid metabolism. We aimed to determine the prevalence of NAFLD, hypertension, and microvascular complications among individuals with T2DM. We assessed their clinical parameters, such as glycemic, lipid, renal, and hepatic values. We also computed and compared the following metabolic indices among patients with and without NAFLD: NAFLD fibrosis score (NFS), fibrosis-4 (FIB4) index, fatty liver index (FLI), and metabolic score for insulin resistance (METS-IR). We further assessed correlations among various clinical parameters and metabolic indices. In addition, we calculated sensitivity, specificity, diagnostic accuracy, and the area under the curve (AUC) for these metabolic indices through a receiver operating characteristic (ROC) curve. Methods This cross-sectional study took place at Kalinga Institute of Medical Sciences (KIMS), Bhubaneswar, India, from March 2023 to February 2025. We reviewed adult diabetic patients of both sexes attending our medicine and endocrinology outpatient departments (OPDs) during the study period. We assessed patients referred for ultrasonography to rule out NAFLD. We evaluated clinical parameters and metabolic indices in patients with and without NAFLD. Associations were measured with Spearman's correlation. We calculated the sensitivity, specificity, AUC, and diagnostic accuracy for these indices. R software (version 4.5.3; R Foundation for Statistical Computing, Vienna, Austria) was used for data analysis. Results Among 401 patients with diabetes (median age 68.0 years), 166 (41.4%) were male. NAFLD was present in 115 (28.7%), and hypertension in 183 (45.6%). Neuropathy, nephropathy, and retinopathy affected 147 (36.7%), 142 (35.4%), and 102 (25.4%) of patients, respectively; these rates were higher in those with NAFLD. Patients with NAFLD had higher median glycated hemoglobin (9.11% vs. 8.61%, p < 0.001), METS-IR (48.22 vs. 47.21, p = 0.024), FLI (66.20 vs. 54.55, p < 0.001), FIB4 (1.02 vs. 0.85, p = 0.010), and NFS (1.39 vs. 1.06, p = 0.002) compared to those without NAFLD. Strong positive correlations were observed between FLI and METS-IR (r = 0.88) and NFS and FIB4 (r = 0.87). FLI and METS-IR showed higher specificity (0.8252 and 0.7630) and accuracy (0.7481 and 0.6434), while FIB4 and NFS had moderate sensitivity and diagnostic accuracy. All indices had similar AUC values (range: 0.5723-0.6222). Conclusion The study found that chronic hyperglycemia is closely associated with increased liver fibrosis, as reflected in higher metabolic index values among patients with NAFLD. Metabolic indices such as FLI, METS-IR, FIB4, and NFS showed moderate utility as non-invasive markers for glycemic control and fibrosis risk. Incorporating fibrosis assessment into routine diabetes management could enable earlier detection and intervention. The findings underscore the importance of further longitudinal studies to clarify whether improved glycemic control can reverse liver fibrosis.

This opinion piece reviews the history of malnutrition related, or malnutrition modulated diabetes mellitus (MMDM). It reviews various terms used to describe this condition, and analyzes current efforts at renaming it as type 5 diabetes. It provides a simple, yet effective diagnostic checklist, based upon Ahuja's diagnostic criteria, for MMDM. While research is certainly required to define and describe this entity, renaming it will create confusion and chaos, rather than comprehension or clarity.

This communication presents a pragmatic approachto describe the phenotypes which match with preferential usage of dual phase insulin or basal insulin+ glucagon-like peptide 1 receptor agonist (GLP1RA)coformulations. A comprehensive evaluation,including severity and style of glycaemia, clinical presentation, comorbidities, complications, and culinary preference, allows efficient choice of insulin formulation. This framework helps in initiation,intensification and interchange of injectable therapy,in an apt, and ept, manner. Keywords: BIAsp, GLP1RA, glargine, insulin, Biphasic insulin, IGlarLixi, lixisenatide, IDegAsp, LisproMix,IDegLira, person centred care, premixed insulin.

The burden of type 2 diabetes mellitus (T2DM) is increasing in India, with increasing mortality and morbidity. In India, T2DM management is complicated by the presence of distinct clinical characteristics as well as certain socioeconomic factors of the patient population. These factors affect glycemic control and lead to poorer outcomes, necessitating the use of add-on treatments with safer medications, which can be used over the long term with minimal follow-up. Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that inhibits the activity of DPP-4, a peptidase that degrades glucagon-like peptide 1 (GLP-1), a glucoregulatory hormone. Sitagliptin enhances glucoregulation in people with T2DM as monotherapy, as well as in combination with other antihyperglycemic drugs, and has a low risk of adverse side effects. This review focuses on assessing the efficacy and safety of sitagliptin as an add-on therapy to other antidiabetic agents and insulin.

PURPOSE OF REVIEW:Given the global rise of MASLD, which impacts approximately one-third of the population, there is a need for earlier diagnosis and effective treatment strategies to avoid long-term hepatic cardiovascular and renal complications. This review summarizes the recent advances in noninvasive diagnosis and new pharmacological agents approved for MASLD. RECENT FINDINGS:The main step forward in diagnostics is a step away from invasive biopsy and emphasis on noninvasive methods including serum biomarkers (e.g. CK-18 and FGF21), imaging (e.g. MRI-PDFF and US-FLI), combination of the two and use of artificial intelligence and machine learning models, for early detection and risk stratification of MASLD and MASH. Multiomics approaches, such as metabolomics and lipidomics, reveal disease-specific signatures, and may help with phenotypic classification of MASLD. Personalized management for MASLD include gut microbiota modulation and point-of-care devices for rapid diagnosis. Novel therapies include THR β agonists, GLP-1/dual GLP-1/GIP agonists, FXR agonists and FGF analogues, which show promise in reducing hepatic fat and fibrosis. SUMMARY:These findings enable earlier MASLD diagnosis and tailored interventions, improving clinical outcomes in primary care and resource-limited settings. Future research should focus on validating cost-effective tools, and developing combination therapies to address the multifaceted nature of MASLD.