By Yasmine S. Ali, MD, MSCI 

 Medically reviewed by David Snyder, PharmD

While several older medications for weight loss (those that have been on the market for at least a decade, and those that have been pulled from the market) have known serious side effects, it hasn’t been until 2016 that the specific cardiovascular effects of the newer weight loss medications have been acknowledged, reviewed, and summarized by cardiovascular experts.

The anti-obesity medications that have been approved by the U.S. Food and Drug Administration (FDA) since 2010 have been of great interest to and a topic of ongoing debate in the cardiology community. Obesity is a known risk factor for cardiovascular disease, and lifestyle changes have long been the mainstay as the first line of therapy.

However, in people in whom lifestyle changes are not enough to induce a sufficient amount of weight loss to make a healthful impact, or in those who have been unable to implement recommended lifestyle changes like a healthy diet and exercise, anti-obesity medications may have a role. These medications may come with cardiovascular risks, though, and until Dr. Vorsanger and colleagues published a review and summary of the cardiovascular effects of these agents in an August 2016 issue of the Journal of the American College of Cardiology, these cardiovascular side effects were not well described.

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Effects of Saxenda (Liraglutide)

Saxenda (liraglutide) was approved by the FDA on December 23, 2014, as a treatment option for chronic weight management. In the United States, Saxenda is marketed by Novo Nordisk, Inc. This drug belongs to a larger class of drugs, known biochemically as glucagon-like peptide-1 (GLP-1) receptor agonists, originally brought to market for the treatment of type 2 diabetes.

The version of Saxenda (liraglutide) that is used for the treatment of diabetes is actually a lower dose of liraglutide that is marketed under the brand name Victoza. Victoza/Saxenda increases the sensitivity of cells in the pancreas to glucose, allowing the pancreas to function more effectively in helping to clear glucose (sugar) from the bloodstream.

Saxenda also delays gastric emptying which may aid in weight loss. Some of the side effects of Saxenda include nausea, which secondarily may decrease appetite and produce weight loss.

But what effects does Saxenda have on the heart? In clinical trials, Saxenda was found to result in a small drop in systolic blood pressure (the top number) of approximately 2.8 millimeters of mercury. However, treatment with Saxenda was also shown to be associated with an increase in heart rate of 3 beats per minute. Older weight-loss drugs that increased heart rate were eventually found to be associated with more serious cardiac side effects, so this is an area of concern and an important area to watch for further research.

It should be noted that, for now, clinical trials such as the SCALE Maintenance trial, which was reported in the International Journal of Obesity by Wadden and colleagues in 2013, have found serious cardiac events (like heart attack and cardiac death) to be rare with Victoza/Saxenda; in fact, such serious events were actually lower in the Victoza/Saxenda group than in the placebo group (those not taking Victoza/Saxenda).

In the SCALE Maintenance trial itself, there was only one death due to heart failure, and that death occurred in the placebo group; the study participants who were taking Victoza/Saxenda had no serious cardiac events at all.

Perhaps most impressive, in the LEADER trial, the cardiovascular results of which were reported online in the New England Journal of Medicine in June 2016, approximately 9,300 patients with diabetes who were at high risk for cardiovascular disease were examined, and after five years, those who were taking Victoza had a lower rate of death due to cardiovascular disease, as well as lower rates of heart attack and stroke.

From such results, many experts are considering more seriously the likelihood that Victoza may actually help prevent cardiovascular disease in patients with diabetes. However, it is very important to note that this conclusion cannot yet be extrapolated to patients without diabetes who are taking Saxenda only for weight loss. The studies needed to evaluate such cardiovascular effects of Saxenda at the 3-milligram dose used for the treatment of obesity have simply not been done.

The Effects of Wegovy (Semaglutide)

Wegovy (semaglutide) was approved by the FDA on June 4, 2021 for chronic weight management in those with at least one weight-related condition (such as high blood pressure, type 2 diabetes, or high cholesterol).1 It is marketed by Novo Nordisk, Inc. Semaglutide was first marketed at lower doses—under the brand name Ozempic—for the treatment of type 2 diabetes.

Wegovy, like Saxenda, is a (GLP-1) receptor agonist.

In clinical trials, Wegovy was shown to be associated with an increased heart rate at rest.2This may be of concern, especially for those at risk of developing certain arrhythmias.

Because Wegovy also causes a delay in gastric emptying, it may have the potential to affect the absorption of other oral medications, including those used to treat heart conditions.

Additional studies are needed to further evaluate the cardiovascular effects of Wegovy.

The Effects of Contrave (Naltrexone/Bupropion)

Contrave (naltrexone/bupropion) was approved by the FDA on September 10, 2014, for the treatment of obesity. It is marketed by Orexigen Therapeutics, Inc., and contains two medications within one pill: naltrexone and bupropion.

Naltrexone, used alone, was originally approved by the FDA as a treatment for opioid addiction and alcohol dependence. Bupropion used alone, has been approved and used for the treatment of depression, seasonal affective disorder (SAD), and smoking cessation.

Together in the extended-release tablet of Contrave, however, the two medications combine to cause weight loss.

Both of these medications have previously been found to have side effects that involve the heart and cardiovascular system. In particular, the effects of Contrave on heart rate and blood pressure appear to be unfavorable. In clinical trials, Contrave was found to increase both blood pressure and heart rate.

On the other hand, the effects of Contrave on the cholesterol profile have been found to be rather favorable, with increases seen in HDL cholesterol (commonly called the “good” cholesterol) and decreases in both LDL cholesterol (the “bad” cholesterol) and triglycerides (fatty acids in the blood).

The Effects of Qsymia (Phentermine/Topiramate)

Qsymia (phentermine/topiramate) was approved by the FDA in 2012 and is marketed by VIVUS. Like Contrave, it also contains two medications within one pill: phentermine and topiramate.

Phentermine by itself can suppress appetite and increase bodily energy expenditure, thereby resulting in weight loss. In fact, phentermine is not a new drug for this purpose, as it was approved in 1959 by the FDA for the short-term treatment of obesity. It has traditionally been limited by certain side effects, however, given that its mechanism of action involves increasing norepinephrine (adrenaline) levels in the body.

Topiramate, on the other hand, has a somewhat unclear mechanism of causing weight loss, with several pathways being postulated, including separate reductions in appetite and adipose (fat) tissue. Topiramate alone, used at a higher dose than the dose that appears in Qsymia, can cause weight loss of 2.2 percent to 5.3 percent of initial body weight.

Qsymia combines both phentermine and topiramate in a single pill and at lower doses than either drug used alone. Qsymia was tested in four clinical trials, and in the end, due to its cardiac side effects, the FDA mandated that information appears on its label stating that its use is not recommended in patients with recent or unstable heart disease.

The cardiac side effects that have been of concern with this medication combination include higher heart rates, with a specific concern for the development of tachycardia (rapid heart rhythm) in certain patients.

Why Is There a Need for Anti-Obesity Medications?

With the American Medical Association (AMA) officially designating obesity as a disease in 2013, over a third (35%) of U.S. adults became the bearers of the latest chronic disease to be associated with increased risk for cardiovascular disease.

Although therapeutic lifestyle changes, through healthy dietary changes and more physical activity, are still the preferred first-line strategy for losing weight, many people with obesity have found it difficult, for various reasons, to achieve adequate weight loss through lifestyle changes alone. Enter the anti-obesity drugs, which address the need for additional medical options for treating obesity.

What Should You Do If You're Taking One of These Drugs?

Always discuss with your healthcare provider any potential side effects of a new medication, and make sure your practitioner knows your full medical history—especially if you have any history of cardiovascular disease, including high blood pressure, heart disease, or stroke.

If you are taking one of the above medications and you experience any of the cardiac side effects listed, or if you begin to experience adverse effects that are not listed but you believe may be due to your medication, be sure to bring this to the attention of your medical provider immediately.

Monitor your blood pressure and heart rate (pulse) while taking these medications, and let your healthcare provider know if you note any significant changes.

Also, keep monitoring your weight. The best way to do this is to weigh yourself at the same time every day. If you are not seeing weight being lost while you are taking one of these medications, then the drug may not be working for you, or other factors may be at play. In either case, talk to your healthcare provider so you can determine whether or not to keep taking the medication.

Sources

Food and Drug Administration. FDA approves new drug treatment for chronic weight management, first since 2014. Published June 4, 2021.

Food and Drug Administration. WEGOVY (semaglutide) injection. Updated June 2021.

Additional Reading

Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311–22. doi:10.1056/NEJMoa1603827

On behalf of the NN8022-1923 Investigators, Wadden TA, Hollander P, et al. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: The SCALE Maintenance randomized study. Int J Obes. 2013;37(11):1443–51. doi:10.1038/ijo.2013.120

Secher A, Jelsing J, Baquero AF, et al. The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss. J Clin Invest. 2014;124(10):4473–88. doi:10.1172/JCI75276

Vorsanger MH, Subramanyam P, Weintraub HS, et al. Cardiovascular effects of the new weight loss agents. J Am Coll Cardiol. 2016;68:849–59. doi:10.1016/j.jacc.2016.06.007

By Yasmine S. Ali, MD, MSCI
Yasmine Ali, MD, is board-certified in cardiology. She is an assistant clinical professor of medicine at Vanderbilt University School of Medicine and an award-winning physician writer.