Association Between the Magnitude of Glycemic Control and Body Weight Loss With GLP-1 Receptor Agonists and Risk of Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-analyses of Randomized Diabetes Cardiovascular Outcomes Trials.

Abstract

Reduction of major atherosclerotic cardiovascular events (MACE) has not been consistent among different glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to assess the association between the magnitude of glycemic control, body weight loss, and reductions in systolic blood pressure (SBP)and low-density lipoprotein cholesterol (LDL-C) achieved through GLP-1 RA therapy and MACE. Electronic databases (MEDLINE, CENTRAL, SCOPUS) were searched through March 2023. Studies were eligible if they were cardiovascular outcome trials (CVOTs) comparing GLP-1 RAs versus placebo in T2DM patients. The outcome of interest was 3-point MACE - cardiovascular death, myocardial infarction, or stroke. Random-effects meta-regression analyses evaluated the associations between reductions of HbA1c, body weight, SBP and LDL-C and reduction of MACE. Overall, 8 CVOTs were included (60079 patients, 30693 with GLP-1 RAs). Reductions of HbA1C were associated with the reduction of 3P-MACE (Log RR -0.290 [95% CI -0.515;-0.064], p = 0.012), with an estimated RR reduction of 25% for each 1% absolute reduction in HbA1C levels. Body weight loss was associated with the reduction of 3P-MACE (Log RR -0.068 [95% CI -0.135;-0.001], p = 0.047), with an estimated RR reduction of 7% for each 1kg reduction in body weight. Reductions of SBP (Log RR -0.058 [95% CI -0.192;0.076], p = 0.396) and LDL-C (Log RR -0.602 [95% CI -4.157;2.953], p = 0.740) were not associated with the reduction of 3P-MACE. In T2DM patients, more potent GLP-1 RAs in reducing HbA1c and body weight were associated with greater reductions of MACE.