Semaglutide Meta-Analysis Finds Lower Mortality and Kidney Events

Key Takeaways

• Semaglutide was linked with lower mortality in the pooled analysis and with fewer major adverse cardiovascular events than placebo.
• Lower rates were also reported for nonfatal myocardial infarction, worsening heart failure, and kidney outcomes.
• No significant effect was observed for nonfatal stroke, while the overall findings favored semaglutide across the cardio-kidney-metabolic continuum.

In a pooled meta-analysis of randomized semaglutide trials, semaglutide was associated with lower all-cause mortality than placebo, with a hazard ratio of 0.84, 95% CI 0.77-0.92, and p = 0.0001. The pooled evidence covered eight randomized placebo-controlled trials involving 39,204 patients across a broad cardio-kidney-metabolic population. Investigators also reported lower rates of cardiovascular death and major cardiovascular and kidney outcomes with semaglutide than placebo. Across the included trial populations, the main reported outcomes generally favored semaglutide.

The analysis pooled randomized controlled trials comparing semaglutide with placebo. Primary outcomes were all-cause mortality and cardiovascular mortality. Secondary outcomes included major cardiovascular and kidney events, and major adverse limb events were exploratory. A random-effects model pooled hazard ratios with 95% confidence intervals across populations spanning the cardio-kidney-metabolic continuum.

In the pooled results, cardiovascular mortality was lower with semaglutide, with HR 0.83, 95% CI 0.72-0.95, and p = 0.0078. Major adverse cardiovascular events were also reduced, with HR 0.82, 95% CI 0.77-0.87, and p < 0.0001. Nonfatal myocardial infarction followed the same pattern, with HR 0.75, 95% CI 0.68-0.84, and p < 0.0001. Together with the lower all-cause mortality reported in the lead finding, these results showed a consistent cardiovascular pattern in the pooled analysis.

Additional outcomes also favored semaglutide in the cardio-kidney-metabolic continuum analysis. Worsening heart failure was lower with semaglutide, with HR 0.84, 95% CI 0.73-0.98, and p = 0.0245, while kidney outcomes were lower with HR 0.83, 95% CI 0.73-0.95, and p = 0.0080. No significant effect was observed for nonfatal stroke. The investigators concluded that semaglutide, versus placebo, was associated with lower all-cause and cardiovascular mortality and with lower major cardiovascular and kidney event rates across the cardio-kidney-metabolic syndrome continuum.