Metabolic efects of antihyperglycemic agents and mortality : meta-analysis of randomized controlled trials

The efects of antihyperglycemic medications on cardiovascular events and mortality are heterogeneous and their efects on intermediate factors might explain these diferences. This systematic review explores the relationship between metabolic factors, mechanism of action, and mortality efects of antihyperglycemic medications in type 2 diabetes. Randomized trials assessing the efects of antihyperglycemic medications on all-cause or cardiovascular mortality in type 2 diabetes were included. Myocardial infarction, stroke, and heart failure were secondary outcomes. The efects of medications on HbA1c, severe hypoglycemia (SH), body weight, systolic blood pressure (SBP), and mechanism of action were evaluated. Meta-analyses and meta-regressions were performed grouping studies according to the above-cited factors. All-cause mortality was lower for medications that reduced HbA1c, SH, body weight, and SBP. Decreased cardiovascular mortality was associated with lower HbA1c, SH, SBP. Myocardial infarction and stroke were also associated with favorable metabolic profle. These fndings were not confrmed in meta-regression models. Medications associated with lower SH, body weight and SBP had a lower risk of heart failure. In conclusion, medications with better metabolic profle were associated with reduced all-cause and cardiovascular mortality. These fndings are based on indirect comparisons and must be applied cautiously