Abstract
OBJECTIVE: This study aimed to estimate population-level effects on weight change of initiating/adhering to additional glucose-lowering medications in adults with type 2 diabetes prescribed metformin. METHODS: We conducted a target trial using electronic health record data from 22,601 patients (age 20 to < 80 years) prescribed metformin to determine initiation/adherence to dipeptidyl peptidase IV (DPP4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium-glucose cotransporter 2 (SGLT-2) inhibitors, long-acting insulin, or sulfonylureas. Inverse probability weighting of marginal structural models with standardization by baseline covariates was used to estimate population-level effects of initiating/adhering to different medications on average 24-month weight change. RESULTS: At 24 months, a mean -5.15 kg (95% CI -10.6, -1.36) and -6.71 kg (95% CI -8.38, -4.34) weight loss would be observed for initiation/adherence to GLP-1RAs and SGLT-2s respectively. At 6 months, weight loss for DPP4s would be observed (-0.89 kg, 95% CI -1.41, -0.32) though not at 12 or 24 months. Glimepiride would be associated with weight gain at 6 and 12 months (0.88 kg, 95% CI 0.44, 1.22; 1.01 kg, 95% CI 0.32, 1.51) but not at 24 months. CONCLUSIONS: Initiation/adherence to GLP-1RAs and SGLT-2s over 24 months could result in average weight losses of 5.15 kg and 6.71 kg, respectively.