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

Mingyue Zheng; Mumtaz Begum; Carla De Oliveira Bernardo; Nigel Stocks; David Gonzalez-Chica

doi:10.1016/j.clinthera.2024.03.001

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

Clin Ther. 2024 Apr 1:S0149-2918(24)00067-5. doi: 10.1016/j.clinthera.2024.03.001. Online ahead of print.

Authors

Mingyue Zheng¹, Mumtaz Begum¹, Carla De Oliveira Bernardo¹, Nigel Stocks¹, David Gonzalez-Chica²

Affiliations

¹ Discipline of General Practice, Adelaide Medical School, University of Adelaide, Adelaide, Australia.
² Discipline of General Practice, Adelaide Medical School, University of Adelaide, Adelaide, Australia; Adelaide Rural Clinical School, University of Adelaide, Adelaide, Australia. Electronic address: david.gonzalez@adelaide.edu.au.

PMID: 38565499
DOI: 10.1016/j.clinthera.2024.03.001

Abstract

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.

Keywords: Drug Prescriptions; Electronic Health Records; Epidemiologic Methods; Evidence–Based Practice; General Practice; Hypoglycaemic Agents; Population Health Management.