Florence Galtier

Aims To investigate the impact of glucose‐lowering therapy‐induced glycated haemoglobin (HbA1c) reduction on the risk of major clinical events according to body weight change and, as a secondary objective, to evaluate the impact of concomitant reductions in HbA1c and body weight on major clinical events. Materials and Methods We searched the MEDLINE and EMBASE databases up to June 30, 2022, for large‐scale studies on glucose‐lowering therapies in which more than 1000 patient‐years of follow‐up in each randomized group were completed. The primary outcome was all‐cause mortality. The study was registered in PROSPERO (CRD42022355479). Results Thirty‐four trials involving 227 220 patients with type 2 diabetes were meta‐analysed using a random‐effects model. Each 1% reduction in HbA1c was associated with a different risk of mortality depending on the ability of glucose‐lowering therapies to induce body weight loss or gain. When glucose‐lowering therapies were associated with weight gain, the risk of mortality increased by 8% (hazard ratio [HR] 1.08, 95% confidence interval [CI] 1.00‐1.16) for each 1% reduction in HbA1c. When glucose‐lowering therapies were associated with weight loss, the risk of mortality was reduced by 22% (HR 0.78, 95% CI 0.72‐0.85) for each 1% reduction in HbA1c. In addition, concomitant reductions in HbA1c and body weight were associated with a significantly lower risk of mortality and vascular events. Conclusions In patients with type 2 diabetes, concomitant reductions in HbA1c and body weight might be more effective in preventing the risk of vascular events and mortality.