Comparing the Effect of Early Versus Delayed Metformin Treatment on Glycaemic Parameters Among Australian Adults With Incident Diabetes: Evidence Using a National General Practice Database

Purpose To compare the effect of early vs delayed metformin treatment for glycaemic management among patients with incident diabetes. Methods Cohort study using electronic health records of regular patients (1+ visits per year in 3 consecutive years) aged 40+ years with ‘incident’ diabetes attending Australian general practices (MedicineInsight, 2011–2018). Patients with incident diabetes were defined as those who had a) 12+ months of medical data before the first recording of a diabetes diagnosis AND b) a diagnosis of ‘diabetes’ recorded at least twice in their electronic medical records or a diagnosis of ‘diabetes’ recorded only once combined with at least 1 abnormal glycaemic result (i.e., HbA1c ≥6.5%, fasting blood glucose [FBG] ≥7.0 mmol/L, or oral glucose tolerance test ≥11.1mmol/L) in the preceding 3 months. The effect of early (<3 months), timely (3–6 months), or delayed (6–12 months) initiation of metformin treatment vs no metformin treatment within 12 months of diagnosis on HbA1c and FBG levels 3 to 24 months after diagnosis was compared using linear regression and augmented inverse probability weighted models. Patients initially managed with other antidiabetic medications (alone or combined with metformin) were excluded. Findings Of 18,856 patients with incident diabetes, 38.8% were prescribed metformin within 3 months, 3.9% between 3 and 6 months, and 6.2% between 6 and 12 months after diagnosis. The untreated group had the lowest baseline parameters (mean HbA1c 6.4%; FBG 6.9mmol/L) and maintained steady levels throughout follow-up. Baseline glycaemic parameters for those on early treatment with metformin (<3 months since diagnosis) were the highest among all groups (mean HbA1c 7.6%; FBG 8.8mmol/L), reaching controlled levels at 3 to 6 months (mean HbA1c 6.5%; FBG 6.9mmol/L) with sustained improvement until the end of follow-up (mean HbA1c 6.4%; FBG 6.9mmol/L at 18–24 months). Patients with timely and delayed treatment also improved their glycaemic parameters after initiating treatment (timely treatment: mean HbA1c 7.3% and FBG 8.3mmol/L at 3–6 months; 6.6% and 6.9mmol/L at 6–12 months; delayed treatment: mean HbA1c 7.2% and FBG 8.4mmol/L at 6–12 months; 6.7% and 7.1mmol/L at 12–18 months). Compared to those not managed with metformin, the corresponding average treatment effect for HbA1c at 18–24 months was +0.04% (95%CI –0.05;0.10) for early, +0.24% (95%CI 0.11;0.37) for timely, and +0.29% (95%CI 0.20;0.39) for delayed treatment. Implications Early metformin therapy (<3 months) for patients recently diagnosed with diabetes consistently improved HbA1c and FBG levels in the first 24 months of diagnosis.