Blood glucose and body weight reduction for the prevention of clinical events and mortality in patients with type 2 diabetes: A meta‐analysis and meta‐regression of 44 randomized controlled trials
Alhassane Diallo, Orianne Villard, Miguel Carlos‐Bolumbu, Philippe Duc, Florence Galtier
Abstract
Abstract Aims The improvement of body weight and glycaemic control on the relative risk of mortality remains unclear. We aimed to investigate the impact of the reduction of body weight or HbA1c on the relative risk of all‐cause mortality with the use of meta‐analysis and meta‐regressions. Materials and methods We searched MEDLINE, CENTRAL and EMBASE databases through March 31, 2025; large‐scale glucose‐lowering therapies with more than 1000 patient‐years of follow‐up in each randomized group were completed. Hazard ratio (HR) and event rate data were extracted for mortality (primary outcome), kidney and cardiovascular outcome (PROSPERO; CRD42022355479). Treatment effects per difference in body weight or HbA1c were estimated using random‐effects meta‐regression. Results Forty‐four trials involving 274 800 patients with type 2 diabetes were meta‐regressed. Compared with placebo or active control, glucose‐lowering therapies reduced the risk of all‐cause mortality (HR 0.93, 95% confidence interval [CI] 0.89–0.96; p < 0.0001), with significant heterogeneity across drug classes (p Interaction = 0.0006). In univariate meta‐regression, 1‐kg difference in body weight between treatment groups was associated with a 3.1% (1.4% – 4.9%) difference in the HR of all‐cause mortality ( p = 0.0003). After adjustment on the reduction in HbA1c, each 1‐kg reduction in body weight remained associated with a 3.4% (1.8% – 5.1%; p < 0.0001) reduction in the risk of all‐cause mortality. In addition, irrespective of the reduction in body weight, each 1% reduction in HbA1c was associated with an 7.6% (0.9% – 14.8%; p = 0.0246) reduction in the risk of all‐cause mortality. Conclusion Reductions in body weight and HbA1c may play a significant role in preventing the risk of major adverse cardiovascular event (MACE) events and mortality.