Plasma metformin concentration as a determinant of metabolic response in adults with type 1 diabetes: a 1-year prospective observational study

Background: Metformin is commonly used as adjunctive therapy in adults with type 1 diabetes (T1DM), although evidence regarding its long-term metabolic effects remains inconsistent. To assess the metabolic effects of adjunctive metformin therapy in adults with type 1 diabetes (T1DM) over a 12-month period, using advanced markers of metabolic control, including time in range (TIR), estimated glucose disposal rate (eGDR), and monitoring of metformin plasma concentrations. Methods: This single-center, observational study included 26 adults with T1DM treated with extended-release metformin (500-2000 mg/day). Metformin plasma concentrations were measured at baseline and at 5 time points up to 12 months using a validated UPLC-MS/MS method. Glycemic control (TIR), insulin dose, anthropometric parameters, lipid profile, visceral adiposity index (VAI), and eGDR were assessed. Participants were grouped by median metformin concentration. Results: Interindividual variability in metformin plasma concentrations was significant. Adjunctive metformin therapy was associated with significant reductions in LDL cholesterol, non-HDL cholesterol, and VAI. A significant transient improvement in eGDR was observed after 6 months of therapy, followed by partial attenuation at 12 months. A significant interaction between metformin concentration subgroup and time was observed for TIR (p = 0.0151), with descriptively greater improvement in participants with higher metformin concentrations. No statistically significant differences in metabolic response were identified between subgroups with lower and higher mean metformin concentrations. Conclusion: Adjunctive metformin therapy in adults with T1DM was associated with favorable changes in insulin sensitivity markers and cardiometabolic risk parameters during follow-up. Monitoring metformin plasma concentrations and eGDR may provide complementary information for metabolic assessment during adjunctive metformin therapy in adults with T1DM.