You’ve likely encountered the stories: while many men successfully cut carbohydrates from their diet and shed 10 pounds, women often find themselves losing just 2 pounds under similar circumstances. This perplexing trend is supported by research, indicating that diet and exercise generally yield better weight loss results for men than women. However, recent clinical trials have brought a refreshing twist to this narrative, revealing that injected GLP-1 weight loss medications demonstrate greater effectiveness for women than for men. Understanding the reasons behind this phenomenon is crucial for optimizing these powerful medications for all patients.
The latest study highlighting this effect was unveiled at the annual meeting of the European Congress on Obesity and published in the New England Journal of Medicine. This research represents the first head-to-head comparison of two injectable GLP-1 medications: semaglutide (marketed as Wegovy) and tirzepatide (known as Zepbound). Approximately 750 individuals suffering from obesity were randomly divided into two groups, with one receiving the maximum tolerable dose of Wegovy and the other receiving the maximum dose of Zepbound. Notably, Zepbound is a newer medication that targets two gut hormones influencing appetite and blood sugar, while Wegovy primarily affects just one.
Many healthcare professionals believe that Zepbound is a more potent medication than Wegovy. This trial, sponsored by Eli Lilly, the manufacturer of Zepbound, found that participants using Zepbound experienced an average weight loss approximately 50% greater than those taking Wegovy, solidifying its position as the superior option for weight loss.
Interestingly, the study revealed that participants lost less weight overall compared to previous trials involving the same medications. This trend was particularly evident among men, who lost about 6% less weight than women. In this study, men represented about 35% of the participants, contrasting with the 20% to 25% male participation seen in earlier trials. Dr. Louis Aronne, who led the study and directs the Comprehensive Weight Control Center at Weill Cornell Medicine, expressed his curiosity about why these medications seem to work better for women, stating, “It has been seen again and again.”
For instance, in a long-term follow-up study comparing semaglutide to a placebo, women lost an average of 11% of their starting weight over two years, while men lost only 8%. Similarly, in trials assessing tirzepatide against a placebo, women lost up to 28% of their initial weight, whereas men lost up to 19%.
Dr. Melanie Jay, an obesity expert and professor at New York University’s Grossman School of Medicine, suggests several factors could explain these observed differences. One potential reason relates to drug dosing; women generally weigh less than men but often receive the same medication doses. Consequently, they might be receiving a comparatively higher dose relative to their body size.
Another possibility revolves around how women store fat. Women typically have more cutaneous fat—the fat located just under the skin—compared to visceral fat, which is stored around internal organs. This difference might influence the effectiveness of GLP-1 medications on various types of fat. Additionally, societal pressures for women to maintain a slimmer figure could drive greater motivation to adhere to medication regimens, even when faced with challenging side effects like nausea and constipation. Dr. Jay has observed that women often find ways to cope with these side effects, demonstrating a higher tolerance than their male counterparts.
Another intriguing factor could be the hormone estrogen, which is present in higher levels in women than in men. Dr. Karolina Skibicka, a professor of molecular medicine at the University of Gothenberg, explores how estrogen interacts with GLP-1 and other gut hormones affecting metabolism. Her research indicates that when estrogen is present, GLP-1's effects are amplified, enhancing its influence on feeding behavior and motivation.
Studies involving rats have shown that administering GLP-1 and estrogen together leads to a significant increase in the effectiveness of these hormones. Conversely, blocking estrogen reduces GLP-1's efficacy, suggesting that estrogen plays a crucial role in enhancing the medication's impact on weight loss.
Despite these insights, much remains unknown about the specific interactions between sex and GLP-1 medications. Both Dr. Jay and Dr. Skibicka emphasize the importance of further research to explore the overlooked sex differences in drug efficacy. While some studies suggest women may lose 50% to 90% more weight than men, they also report higher instances of gastrointestinal side effects. Conversely, men seem to gain more cardiovascular benefits from these medications.
Understanding these differences is vital for developing effective treatment strategies tailored to individual needs. Insights into how estrogen affects medication efficacy could lead to improved treatment options for women, particularly those undergoing hormone-blocking therapies or experiencing menopause. Dr. Jay points out that recognizing and addressing these biological differences could enhance adherence to medications and overall treatment outcomes.
In conclusion, the growing body of research surrounding GLP-1 weight loss medications highlights significant gender disparities in efficacy. As scientists continue to unravel the complexities of these differences, there is hope for more personalized and effective approaches to weight loss treatment for both men and women.
