GLP-1 RAs reduce deaths, MACE in at-risk individuals

Treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) results in a decrease in deaths and major adverse cardiovascular events (MACE) in high-risk patients, reports as study.

A team of investigators performed a meta-analysis on relevant trials comparing GLP-1 RAs with controls or placebo. They also conducted analyses in prespecified subgroups based on the GLP-1 RA used and subgroups according to diabetes mellitus, kidney function, obesity, or heart failure.

Twenty-one trials, including a total of 99,599 patients, met the eligibility criteria. Eight different GLP-1 RAs were used, namely lixisenatide, liraglutide, exenatide, semaglutide, efpeglenatide, dulaglutide, albiglutide, and tirzepatide. Each of these drugs was administered at therapeutic doses and compared with placebo or controls.

Over a mean follow-up of 2.4 years, GLP-1 RAs reduced all-cause mortality (incidence rate ratio [IRR], 0.88, 95 percent confidence interval [CI], 0.84–0.92; number needed to treat [NNT]=121), cardiovascular death (IRR, 0.87, 95 percent CI, 0.81–0.92; NNT=170), and MACE (IRR, 0.87, 95 percent CI, 0.83–0.91; NNT=66) relative to controls.

Moreover, the use of GLP-1 RAs helped reduce serious adverse events (–9 percent), myocardial infarction (–15 percent), acute kidney failure (–9 percent), heart failure (–15 percent), and infections (–10 percent) but led to more gastrointestinal (63 percent) and gallbladder disorders (26 percent).

No significant between-group differences were noted in stroke, pancreatitis, or neoplasm, and results were consistent across subgroups. Furthermore, analysis by GLP-1 RA type revealed potential variations in efficacy and safety profiles.

“GLP-1 RAs reduce mortality and MACE in high-risk populations, highlighting benefits beyond glycaemic control. These come at increased gastrointestinal and gallbladder risks,” the investigators said. 

“Variation in efficacy and tolerability supports tailoring GLP-1 RA therapy to individual patient characteristics and treatment goals,” they added.