Semaglutide drugs aid weight loss and heart health but does that come at the expense of gut health? Image credit: Douglas Cliff/Getty Images.

• Diabetes medications based on semaglutide deliver important cardiovascular benefits, according to a new meta-analysis.
• Untangling different health benefits resulting from semaglutide from those resulting from weight loss can be difficult. The authors used statistical tools to reach a clearer view of semaglutide’s cardiovascular benefits.
• The meta-analysis also investigated frequently reported gastrointestinal adverse effects accompanying the medication, as well as their connection to patients discontinuing treatment with semaglutide.

The diabetes medication semaglutide — sold under brand names including Ozempic, Wegovy, and Rybelsus — which has also gained popularity as a weight-loss tool, has another significant health benefit, a new meta-analysis suggests.

Only Wegovy has received Food and Drug Administration (FDA) approvalTrusted Source as a weight-management treatment in obesity so far, although the other two medications are widely used for this purpose off-label.

The meta-analysis found that use of semaglutide is associated with a significant reduction in cardiovascular risk.

Its authors found that use of semaglutide reduced:

• deaths from causes related to cardiovascular disease by 17%
• hospitalizations for heart failure by 76%
• non-fatal myocardial infarction (heart attack) by 24%
• the need for coronary revascularization by 24%
• strokes in people with diabetes by 35%
• deaths from any cause by 21%.

The meta-analysis appears in the International Journal of Obesity.

What semaglutide dosage is linked to side effects?

Since weight loss itself is also associated with a reduction in cardiovascular risk, it has been unclear how much of that benefit can be directly attributed to semaglutide itself and how much is a product of maintaining a healthier weight.

The recent meta-analysis encompassed 38 studies and included individuals with and without diabetes.

Its authors also investigated the effect of semaglutide dose sizes on adverse gastrointestinal effects for both subcutaneous injection and orally taken versions of the drug. These side effects include stomach pain, nausea, constipation, and/or diarrhea.

People receiving the 2.4 milligram (mg) dose of semaglutide reported the highest number of gastrointestinal adverse effects, and patients using subcutaneous semaglutide had a higher frequency in general of gastrointestinal side effects.

The researchers found no difference between subcutaneous and oral semaglutide for constipation. A 50 mg dose was associated with a higher occurrence of adverse effects apart from constipation compared to 3 mg, 7 mg, 14 mg, and 25 mg doses.

How do we know semaglutide offers heart benefits?

First author of the meta-analysis, André Saad, a medical student at the State University of Ponta Grossa in Paraná, Brazil, told Medical News Today that: “Weight loss is closely related to improved cardiovascular health, especially in patients who have developed heart failure. Therefore, a study like ours is not able to separate the effect of weight loss and medication on cardiovascular events.”

Jayne Morgan, MD, a cardiologist and the Executive Director of Health and Community Education at the Piedmont Healthcare Corporation in Atlanta, GA, who was not involved in the meta-analysis, also noted that “[the meta-analysis] does seem to address this with the random effects model which can be a powerful tool statistically, allowing the capture of the variability in weights across the studies.”

Certain effects of semaglutide are already known to affect heart health directly, said Saad, who further pointed out that the drug “stabilizes atherosclerotic plaques, preventing the development of an acute myocardial infarction,” and “improves systemic inflammation caused by obesity.”

“Semaglutides,” said Morgan, “act directly on blood vessels by improving blood flow to the heart and lowering blood pressure, on the kidneys by reducing the rate of GFR [glomerular filtration rate] decline, on the liver by reducing steatosis and improving cholesterol profile, and also on the central nervous system.”

If semaglutide provides direct cardiovascular benefits, does the meta-analysis imply the drug may have value for people at risk of cardiovascular disease who do not have diabetes, overweight, or obesity? “This study most certainly does imply that,” said Morgan.

“There appears to be great promise for this entire class of GLP1-RA [GLP-1 receptor agonist] drugs, and semaglutides in particular. They currently appear to be best in class for cardiovascular risk reduction and HFpEF [heart failure with preserved ejection fraction ] reduction in hospitalizations, [with a] 35% reduction in the risk of stroke in those with type 2 [diabetes].”

– Jayne Morgan, MD

Oral semaglutide linked to fewer all-cause deaths

The meta-analysis found that oral semaglutide was superior to the subcutaneous version at reducing all-cause mortality.

“I believe that better adherence and fewer adverse effects associated with the oral route contribute to better use of the medication and, consequently, led to this good result,” Saad hypothesized.

“However, caution must be taken when interpreting results from the oral route, as there is only one large study of this route that evaluated cardiovascular outcomes,” he emphasized.