New weight-loss drugs yield cardiovascular benefits—along with adverse effects

By Yasmine S. Ali, MD, MSCI, FACC, FACP | Fact-checked by Barbara Bekiesz
Published February 19, 2024

Key Takeaways

  • Weight-loss drugs like semaglutide and liraglutide—originally approved for type 2 diabetes—have shown cardiovascular benefits in recent clinical trials, but GI side effects are becoming more apparent as more patients take them.

  • Tirzepatide is a novel GLP-1 agonist and glucose-dependent insulinotropic polypeptide that improved cardiometabolic measures in a large clinical trial, but also caused gastrointestinal side effects.

  • While new pharmacologic options for weight loss represent progress, lifestyle interventions encouraging healthy diet and exercise should not be abandoned.

Overweight and obesity affect the world population in epidemic proportions, with more than 70% of US adults and more than 50% of the global population included in these diagnoses.[] Until recently, however, few pharmacologic agents were available for the safe and effective treatment of excess body weight.

Various weight-loss drugs have seen a significant uptick in approvals, uses, and new indications recently, largely due to favorable clinical data.

In particular, cardiovascular benefits have been demonstrated for certain agents, some of which may be prescribed for a BMI as low as 27 kg/m2 when a weight-associated comorbidity is present.

Obesity has been associated with several forms of cardiovascular disease (CVD), including hypertension, heart failure, atherosclerotic CVD, and atrial fibrillation, as well as CVD risk factors like dyslipidemia, type 2 diabetes mellitus, and obstructive sleep apnea.[]

Until recently, however, few pharmacologic agents were available for the safe and effective treatment of excess body weight.

Some of the most promising new agents are those that were originally developed for the treatment of type 2 diabetes.


Semaglutide, which has the distinction of being the first oral glucagon-like peptide 1 (GLP-1) agonist, was initially approved for treatment of type 2 diabetes. It is also one of the agents that has recently shown favorable results in clinical trials examining CVD outcomes.

In the SELECT trial, semaglutide was found to be superior to placebo in reducing the incidence of death from CVD, nonfatal myocardial infarction (MI), or nonfatal stroke at a mean follow-up of 39.8 months in patients with pre-existing CVD and overweight or obesity who did not have diabetes.[]

At the current pricing for GLP-1 receptor agonists, however, this treatment remains inaccessible to many patients—and there are serious adverse effects that must be acknowledged.

In June 2023, for example, the American Society of Anesthesiologists released new recommendations for patients to stop taking GLP-1 agonists before elective surgery due to the potential for vomiting while under anesthesia.[]

"When treating millions of people with medications like semaglutide, even relatively rare side effects will occur in a large number of people."

Susan Yanovski, MD

In October 2023, researchers reported dangerous gastrointestinal complications, such as pancreatitis and bowel obstruction, as well as gastroparesis, in patients with obesity who were taking GLP-1 agonists.[] As Susan Yanovski, MD, senior scientific advisor for clinical obesity research and co-director of the Office of Obesity Research at the National Institute of Diabetes and Digestive and Kidney Diseases, told JAMA, “When treating millions of people with medications like semaglutide, even relatively rare side effects will occur in a large number of people.”[]


Another GLP-1 agonist originally approved for type 2 diabetes, liraglutide, has been found to have cardiovascular benefits as well. In the LEADER trial, patients randomized to liraglutide had a significant reduction in major adverse cardiovascular events after a median follow-up of 3.8 years. 

Despite a known side effect of an increased heart rate, a subsequent analysis found that there was no increased risk of heart failure hospitalization with liraglutide.[]


In the SURMOUNT-1 trial, treatment with tirzepatide, a novel GLP-1 agonist and glucose-dependent insulinotropic polypeptide, resulted in improvements in all prespecified cardiometabolic measures. However, as with other GLP-1 agonists, the most common adverse events were gastrointestinal and occurred primarily during dose escalation.[]

Longer-term, real-world safety data needed

Given how recently these drugs have been introduced to the broader, real-world market, post-market surveillance and adverse event reporting will be followed closely to determine how safe they really are in the general patient population for whom they are intended. Obesity and lifestyle medicine experts also continue to remind the public and our colleagues that we must not abandon efforts to encourage healthy lifestyle changes and systemic obesity-prevention measures.

What this means for you

These new pharmacologic options for weight management provide additional tools to consider when treating patients with overweight and obesity, especially those with CVD risk factors like diabetes. However, they come with concerning GI and other side effects that warrant close patient monitoring and realistic conversations about expected outcomes. 

Lifestyle modifications remain essential, so be prepared to counsel patients on diet, physical activity, and behavioral changes as well. Ultimately, more data is needed to determine the risk/benefit ratio of chronic use of these agents in broad, real-world populations.

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