Effects of Premeal Versus Postmeal Metformin Administration on Postmeal Glycemic Control in Individuals With Type 2 Diabetes Mellitus: A Randomized, 8-Week Crossover Study

Abstract

Aims: To evaluate the effects of premeal versus postmeal metformin administration on postmeal glycemic control in individuals with type 2 diabetes mellitus receiving metformin monotherapy. Methods: All participants were randomly assigned to receive immediate-release metformin either 30–60 min before or immediately after meal for 4 weeks, and crossed over to the alternate regimen for another 4 weeks. Standardized mixed-meal tests with glucose and insulin measurements were performed, and fructosamine was measured at baseline and at the end of each intervention. Continuous glucose monitoring (CGM) was applied to all during the last week of each intervention. Data were expressed as mean ± SD or estimated mean [95% CI] and were analysed using multilevel mixed-effects linear regression. The primary objective was to compare postmeal glucose responses to a standardized mixed-meal between groups. Secondary objectives were to assess CGM-derived postmeal glucose, fructosamine and insulin responses to a standardized mixed-meal. Results: Twenty-two women (age 49.5 (Formula presented.) 9.7 years, BMI 29.1 (Formula presented.) 5.0 kg/m², HbA1c 7.0% (Formula presented.) 0.3%) were enrolled and only 20 were analysed. Glucose incremental area under curve (iAUC, mg/dL.h) after a standardized mixed-meal was significantly lower in the premeal group at 0–1 h (31.4[23.8–38.9] vs. 38.3[30.8–45.9]; p = 0.034) and 0–2 h (79.1[57.9–100.3] vs. 96.3[75.1–117.5]; p = 0.035). CGM showed significantly lower glucose iAUC at 0–1 h (17.4[13.5–21.3] vs. 22.7[18.8–26.6]; p < 0.001), 0–2 h (54.5[46.1–63.0] VS 69.6[61.1–78.0]; p < 0.001), and 0–3 h (78.5[66.3–90.7] vs. 95.9[83.6–108.2]; p = 0.008) in the premeal group. Fructosamine and insulin levels did not differ between groups. Conclusions: Premeal immediate-release metformin reduces postmeal glycemic excursions more effectively than postmeal administration. This simple timing strategy may provide benefit for individuals who have predominant postmeal hyperglycemia. Trial Registration: Thai Clinical Trials Registry number: 20241127004.