Effect of glucagon-like peptide-1 receptor agonists in subjects with type 2 diabetes mellitus: A meta-analysis

What is known and objective We performed a meta-analysis to evaluate the effects of glucagon-like peptide-1 receptor agonists compared to placebo on cardiovascular, kidney-related, and eye-related disease outcomes or on mortality in subjects with type 2 diabetes mellitus. Methods A systematic literature search up to April 2021 was performed, and 8 studies included 61,661 subjects with type 2 diabetes mellitus at the start of the study, 29,034 of them were using glucagon-like peptide-1 receptor agonists and 32,627 were given a placebo. They reported on relationships between the effects of glucagon-like peptide-1 receptor agonists compared to placebo on mortality rates, cardiovascular, renal and ophthalmic outcomes in subjects with type 2 diabetes mellitus. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) to assess the effects of glucagon-like peptide-1 receptor agonists compared to placebo on the listed outcomes on subjects with type 2 diabetes mellitus, using the dichotomous method with a random or fixed-effect model. Results The use of glucagon-like peptide-1 receptor agonists was associated with significantly lowered all-cause mortality (OR, 0.76; 95% CI, 0.65-0.89, p < 0.001), cardiovascular deaths (OR, 0.87; 95% CI, 0.81-0.94, p < 0.001), myocardial infarctions (OR, 0.92; 95% CI, 0.85-0.98, p = 0.01), strokes (OR, 0.81; 95% CI, 0.74--0.90, p < 0.001), hospital admissions owing to heart failure (OR, 0.91; 95% CI, 0.83-1.00, p = 0.04) and renal events (OR, 0.83; 95% CI, 0.77-0.89, p < 0.001) compared to placebo in subjects with type 2 diabetes mellitus. However, glucagon-like peptide-1 receptor agonists had significantly higher ophthalmic events (OR, 1.15; 95% CI, 1.04-1.29, p = 0.009) compared to placebo in subjects with type 2 diabetes mellitus. What is new and conclusion Glucagon-like peptide-1 receptor agonists may have a lower risk of all-cause mortality, cardiovascular death, myocardial infarction, stroke, hospital admission owing to heart failure and renal events compared to placebo in subjects with type 2 diabetes mellitus. However, they have significantly higher ophthalmic events compared to placebo in subjects with type 2 diabetes mellitus. Further studies are required to validate these findings.