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PubMed15 Apr 2026·Diabetes, obesity & metabolism● 5/10i

GLP-1, GIP, and Glucagon Excursions During a Mixed Meal Tolerance Test in Young and Lean South Asians Versus Europids.

Hoekx CA, Brinkman LBD, van Eenige R, Kooijman S, Muskiet M et al.

South Asian adults showed biphasic glucose response to meals versus monophasic response in European adults, with sex-specific differences in GLP-1, GIP, and glucagon patterns despite similar BMI. Mixed meal tolerance test in 49 young, lean adults (24 South Asian, 25 European) over 240 minutes. This represents first detailed comparison of incretin hormone responses between these populations, revealing distinct metabolic phenotypes that could affect GLP-1 therapy responses. The findings suggest South Asians may need different dosing strategies or combination approaches for optimal glycemic control.

Strategic signal

The biphasic glucose response and altered incretin patterns in South Asians could require population-specific clinical development for GLP-1 therapies. Regulatory agencies may demand ethnicity-specific efficacy data, particularly as South Asian populations represent large markets in the US, UK, and globally. This mirrors earlier concerns about differential SGLT2 responses across ethnic groups that led to label modifications. Companies developing oral GLP-1s like Eli Lilly's orforglipron may need additional studies to demonstrate comparable efficacy across populations.

GLP-1Type 2 diabetesMechanismsEli Lilly

Original Abstract

AIMS: South Asians exhibit an unfavourable metabolic phenotype characterized by visceral obesity, insulin resistance and dyslipidemia. While various hormones play a critical role in regulating postprandial energy metabolism, it remains unclear whether they respond differently to food intake. We aimed to compare the meal-induced excursion of incretin hormones (GLP-1 and GIP) and glucagon between South Asians and Europids. MATERIALS AND METHODS: Forty nine young, lean South Asian (n = 24), and Europid (n = 25) males and females underwent an extended (up to 240 min) mixed meal tolerance test (MMTT). At seven time points circulating incretins (active and total GLP-1 and GIP), glucagon, and parameters related to glucose (i.e., glucose, insulin) and lipid metabolism were measured. RESULTS: In response to the MMTT, Europids generally exhibited a single peak in glucose levels at t = 30 min, while South Asians tended to display a biphasic glucose response, with peaks at t = 30 and t = 90 min. Among South Asian males, this was accompanied by an increased insulin response, characterized by elevated levels at the corresponding glucose peaks. South Asian females, however, demonstrated a marked drop in circulating glucagon at t = 90 min, and biphasic excursions of total and active GLP-1 and GIP (t = 30 and t = 120 min). Postprandial lipid excursions did not differ between ethnicities. CONCLUSIONS: In contrast to a monophasic glucose response to the MMTT of Europids, South Asians tended to exhibit a biphasic glucose response, with sex-specific hormonal patterns, suggesting altered incretin and insulin dynamics despite similar postprandial lipid excursions. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05829018; registration date: 25-04-2023).

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