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

Dimitris Varvaki Rados,Lana Catani Pinto,Jorge Luiz Gross,Cristiane Bauermann Leitão,Camila Viecceli,Fernando Gerchman

doi:10.1038/s41598-020-69738-w

Dimitris Varvaki Rados, Lana Catani Pinto + Show 4 more

Open Access

https://doi.org/10.1038/s41598-020-69738-w

Copy DOI

Abstract

The effects of antihyperglycemic medications on cardiovascular events and mortality are heterogeneous and their effects on intermediate factors might explain these differences. This systematic review explores the relationship between metabolic factors, mechanism of action, and mortality effects of antihyperglycemic medications in type 2 diabetes. Randomized trials assessing the effects 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 effects 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 profile. These findings were not confirmed 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 profile were associated with reduced all-cause and cardiovascular mortality. These findings are based on indirect comparisons and must be applied cautiously.

Highlights

The effects of antihyperglycemic medications on cardiovascular events and mortality are heterogeneous and their effects on intermediate factors might explain these differences
Joint guideline from the European Association for the Study of Diabetes and American Diabetes Association recommend a patient-centered approach[15]. This is based on the selection of medications in type 2 diabetes based on patient factors and considering the heterogeneity of treatment options, such as weight effects, hypoglycemia
We evaluated all-cause mortality and cardiovascular mortality as primary outcomes and the incidence of cardiovascular events as secondary outcomes

Summary

Introduction

The effects of antihyperglycemic medications on cardiovascular events and mortality are heterogeneous and their effects on intermediate factors might explain these differences. Cardiovascular safety trials showed that some sodium-glucoselinked cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are capable of reducing cardiovascular events and all-cause mortality in high-risk p opulations[8,9,10,11]. These medications have different mechanisms of action and effects on glucose values, they share similar favorable metabolic effects, such as weight loss, and reduced risk of hypoglycemia[12]. This is based on the selection of medications in type 2 diabetes based on patient factors and considering the heterogeneity of treatment options, such as weight effects, hypoglycemia

Objectives

Methods

Results

Conclusion