Do patients with prediabetes managed with metformin achieve better glycaemic control? A national study using primary care medical records

Aims: To estimate the effectiveness of metformin on glycaemic parameters among participants with incident prediabetes attending Australian general practices.Methods: This retrospective cohort study used electronic health records of regular participants (3+ visits in two consecutive years) attending 383 Australian general practices (MedicineInsight). Participants with 'incident' prediabetes (newly recorded diagnosis between 2012 and 2017) and their glycaemic parameters (haemoglobin A1c [HbA1c] or fasting blood glucose [FBG]) at 6-, 12-, and 18-24 months post diagnosis (unexposed) or post-management with metformin (treatment) were identified from the database. We estimated the average treatment effect (ATE) of metformin management on glycaemic parameters using both linear regression and augmented inverse probability weighting.Results: Of the 4770 investigated participants with 'incident' prediabetes, 10.2% were managed with metformin. Participants on metformin had higher HbA1c levels at the baseline than those unexposed (mean 45 mmol/mol [6.2%] and 41 mmol/mol [5.9%], respectively), but no differences were observed at 6-12 months (mmol/mol ATE 0.0, 95% CI -0.4; 0.7) or 12-18 months (ATE -0.3, 95% CI -1.2; 0.3). However, participants on metformin had lower mean HbA1c mmol/mol at 18-24 months (ATE -1.1, 95% CI -2.0; 0.1) than those unexposed. Consistent results were observed for FBG (ATE at 6-12 months -0.14 [95% CI -0.25; -0.04], 12-18 months 0.02 [95% CI -0.08; 0.13] and 18-24 months -0.07 [95% CI -0.25; 0.12]).Conclusion: The higher HbA1c and FBG baseline levels among participants with 'incident' prediabetes managed with metformin improved after 6-12 months of starting pharmacological management, and the effect persisted for up to 24 months. Management with metformin could prevent further deterioration of glycaemic levels.