- 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.
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:
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.
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
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.
It is not uncommon for adverse effects to cause a semaglutide patient to discontinue their medication, says the meta-analysis.
For people taking between 0.5 mg and 2.4 mg of subcutaneous semaglutide, nausea increased from 23% of those taking 0.5 mg to 68% of those taking 2.4 mg, and vomiting increased from 9% to 45%.
Of subcutaneous semaglutide users, 9% to 11% decided to stop treatment due to adverse effects.
With oral semaglutide, the number of people discontinuing treatment due to adverse effects rose steadily according to dose from 3 mg to 25 mg, and then began decreasing at 50 mg.
While adverse effects can be difficult to manage, Saad underscored the importance of viewing the continuation of obesity treatment as being as important as any other chronic condition’s ongoing treatment would be.
He asked: “What would happen if a person with diabetes stopped taking their medication? It would worsen your blood sugar levels. What if a person with high blood pressure did not take their antihypertensive medication? Your blood pressure would increase.”
“The reasoning is the same for obesity,” Saad asserted, “since, like diabetes mellitus and hypertension, it is a chronic disease, and must be treated accordingly.”
“It is clear,” he said, “that treatment must be individualized, and that some patients can gradually reduce medication, but this does not happen with the majority, and early cessation of treatment can lead to weight regain.”
Mir Ali, MD, a board-certified general surgeon, bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA, who was not involved in the meta-analysis, suggested several ways to help avoid adverse gastrointestinal effects, the first of which is limiting dose sizes as much as possible.
“We start the patient on the lowest dose,” said Ali, “and adjust it every 4 weeks. It typically gives patients time to adapt to these side effects. We do have patients who are seeing results on lower doses.”
People taking semaglutide, he emphasized, “really have to eat slow because [semaglutide] does affect the emptying of the stomach.”
“Sometimes, people are taking these medications and eating like they did before. They get over-full, and that causes more nausea because the stomach is not emptying like it did before,” explained Ali.
He added that he and his colleagues “advise […] patients to reduce carbohydrate intake and stick to protein and vegetables that are going to facilitate weight loss. [These types of foods] also help to minimize some of the symptoms.”
In extreme cases, doctors can prescribe anti-nausea medication.
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