Obesity drugs under review: Semaglutide, tirzepatide, naltrexone/bupropion all boost heart health
Obesity management medications (OMMs) have exploded in popularity in recent years, a trend highlighted by the success of GLP-1 drugs such as semaglutide and tirzepatide. To learn more about OMMs, and help identify the various advantages associated with each treatment option, a team of researchers has evaluated the safety and effectiveness of six popular OMMS. The group shared its findings in Nature Medicine.[1]
“Obesity is an adiposity-based chronic disease driven by biological mechanisms, resulting in dysregulation and/or excess accumulation of adipose tissue,” wrote first authors Barbara McGowan, PhD, a consultant with Guyʼs & St. Thomasʼ NHS Foundation Trust, and Andreea Ciudin, PhD, coordinator of the Comprehensive Obesity Treatment Unit at Vall d’Hebron University Hospital, and colleagues. “The biology of obesity includes genetic predisposition, neurohormonal signaling disruptions (particularly in the hypothalamus) and alterations in appetite-regulating hormones. Furthermore, the body defends against fat loss through mechanisms including reduced resting energy expenditure and increased hunger, making long-term weight maintenance challenging. As a result, lifestyle interventions alone, such as diet and exercise, are often insufficient, and effective management typically requires a combination of strategies to address the underlying biology of obesity.”
The group explored data from more than 60,000 patients who originally participated in one of 56 randomized controlled trials (RCTs). All but two of the RCTs included a placebo.
Cardiovascular outcomes played a critical role in this research. While 33 RCTs tracked major adverse cardiovascular events (MACEs), 37 RCTs tracked cardiovascular mortality and another seven tracked heart failure hospitalizations.
Obesity management medications in this meta-analysis include:
- Semaglutide is a GLP-1 receptor agonist sold by Novo Nordisk under the brand names Wegovy and Ozempic.
- Tirzepatide is a popular dual GIP/GLP-receptor agonist sold by Eli Lilly and Company under the brand names Zepbound and Mounjaro.
- Liraglutide is a GLP-1 receptor agonist sold by Novo Nordisk under the brand names Victoza and Saxenda.
- Naltrexone/bupropion is a combination medication sold by Currax Pharmaceuticals under the brand name Contrave.
- Phentermine/topiramate is a combination medication sold by Vivus under the brand name Qsymia.
- Orlistat is a popular weight loss medication sold by multiple pharmaceutical companies under a number of brand names.
Cardiovascular outcomes and other key takeaways
Overall, the authors found that all six OMMs were associated with significant improvements in weight loss compared to a placebo. The greatest difference was seen with semaglutide and tirzepatide.
In addition, both semaglutide and tirzepatide were linked to evidence of normoglycemia restoration, a remission of type 2 diabetes and a reduction in heart failure hospitalizations.
Semaglutide was the only medication that significantly lowered a patient’s MACE risk. The only treatments associated with a lower risk of cardiovascular mortality, on the other hand, were semaglutide and naltrexone/bupropion.
The group also noted that “all OMMs demonstrated a generally favorable safety profile.” The only one linked to any sort of increase in the risk of a serious adverse event was naltrexone/bupropion.
“The long-term safety of these medications, including their potential associations with cancer risk and other uncommon events, warrants further investigation,” the authors added.
Finally, the researchers noted that choosing the optimal OMM for any specific patient population is “beyond the scope” of their analysis. However, they did say such decisions should be based on multidisciplinary discussions that take the patient’s full medical history into account.
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Michael has more than 19 years of experience as a professional writer and editor. He has written at length about cardiology, radiology, artificial intelligence and other key healthcare topics.