For patients with type 2 diabetes mellitus (T2DM) who continue to experience postmeal hyperglycemia while receiving metformin monotherapy, adjusting medication timing may improve glycemic control without increasing treatment intensity. In a randomized crossover study published in Diabetes, Obesity and Metabolism, immediate-release metformin taken before meals lowered postmeal glucose excursions more effectively than administration immediately after meals.
The trial evaluated adults receiving metformin monotherapy and enrolled 22 women, of whom 20 were analyzed. Mean age was 49.5 ± 9.7 years, mean body mass index (BMI) was 29.1 ± 5.0 kg/m², and mean glycated hemoglobin (HbA1c) was 7.0% ± 0.3%. Participants were randomly assigned to take immediate-release metformin either 30 to 60 minutes before meals or immediately after meals for 4 weeks, then crossed over to the alternate regimen for an additional 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 treatment phase. Continuous glucose monitoring (CGM) was applied to all participants during the last week of each intervention period. Data were analyzed using multilevel mixed-effects linear regression and reported as mean ± standard deviation or estimated mean with 95% confidence intervals.
The primary endpoint was postmeal glucose response during the standardized mixed meal. Premeal dosing significantly reduced glucose incremental area under the curve (iAUC) at 0 to 1 hour versus postmeal dosing (31.4 [95% CI, 23.8-38.9] vs 38.3 [30.8-45.9] mg/dL·h; P=0.034). Glucose iAUC at 0 to 2 hours was also lower with premeal administration (79.1 [57.9-100.3] vs 96.3 [75.1-117.5] mg/dL·h; P=0.035).
CGM findings were consistent with meal-test results. Premeal dosing lowered glucose iAUC at 0 to 1 hour (17.4 [13.5-21.3] vs 22.7 [18.8-26.6]; P<0.001), 0 to 2 hours (54.5 [46.1-63.0] vs 69.6 [61.1-78.0]; P<0.001), and 0 to 3 hours (78.5 [66.3-90.7] vs 95.9 [83.6-108.2]; P=0.008).
Secondary analyses showed no between-group differences in fructosamine or insulin levels. The findings suggest that taking immediate-release metformin before meals may be a practical strategy for individuals with predominant postmeal hyperglycemia.
