GLP-1 drugs have gained significant attention for their dual ability to manage diabetes and promote substantial weight loss while reducing “food noise.” However, like many medications, they come with a spectrum of side effects, both beneficial and adverse, that users may experience. These medications, including Ozempic and Wegovy (semaglutide), Victoza and Saxenda (liraglutide), and Mounjaro and Zepbound (tirzepatide), are currently used for weight loss, although not all are specifically approved for this purpose. As more options like retatrutide emerge, understanding their effects becomes crucial.
The Not-So-Good News
Muscle Loss
When individuals lose 15 to 25 percent of their body weight, 10 to 20 percent of that loss can be lean mass, including muscle and bone. This is a common outcome of any weight loss, not just when using these medications. Strength training can mitigate this effect. A study on liraglutide (Saxenda) revealed that participants who engaged in strength training four times a week maintained muscle mass better than those who only took the medication or only exercised. Paul Titchenell, PhD, from the University of Pennsylvania, advises ensuring a diet rich in muscle-building protein.
Potential for ED
While erectile dysfunction (ED) is often mentioned as a potential side effect, Jyotsna Ghosh, M.D., an obesity medicine physician at Johns Hopkins Medicine, notes the lack of substantial data supporting this claim. In fact, improved blood flow and reduced inflammation from weight loss might alleviate ED. Wajahat Mehal, M.D., director of the Yale Weight Loss Program, adds that weight loss and improved diabetes management may naturally reduce ED incidence.
Queasiness and Digestive Issues
GLP-1s can affect a chemoreceptor in the brain stem, leading to nausea, particularly with semaglutide. Kevin Williams, PhD, from the University of Texas Southwestern Medical Center, explains that this is the most common side effect. Tirzepatide, however, is associated with less severe digestive side effects, including constipation, due to its action on two receptors. Dr. Mehal notes that tirzepatide predominantly targets the GIP receptor, which induces less nausea.
Gallstones
These medications can slow bile movement, increasing the risk of gallstones, gallbladder inflammation, and bile duct issues. Dan Azagury, MD, a bariatric surgeon at Stanford, explains that rapid weight loss alters bile composition, leading to sandy deposits. Gallstones can cause sudden, intense pain in the upper right abdomen after eating. Immediate medical attention is advised if symptoms occur.
Sagging Skin
Rapid weight loss can lead to “Ozempic face,” characterized by sagging cheeks and deep wrinkles. Patricia Mars, MD, a plastic surgeon in Tucson, explains that skin fibers do not rebound well after being stretched. Clinton Humphrey, MD, a facial plastic surgeon at the University of Kansas Medical Center, suggests consulting a dermatologist for treatments like topical vitamin C, retinoids, injectables, or surgery.
Fatigue and Loss of Pleasure
Fatigue and anhedonia, or loss of pleasure, are common side effects that can decrease motivation for exercise. Dr. Ghosh advises discussing these symptoms with a doctor to adjust the medication dose or type if necessary.
The Good News
A Healthier Heart
GLP-1s significantly reduce the risk of heart attacks, strokes, and cardiovascular disease-related deaths. A review in the Journal of Endocrinology credits not only weight loss but also the drugs’ ability to lower blood sugar, blood pressure, cholesterol, and inflammation. Dr. Mehal highlights that semaglutide research shows a 20 percent reduction in cardiovascular events over three years in high-risk groups.
Fewer Cravings
GLP-1s help reduce overeating and may also aid in addressing addictions like alcohol, smoking, and opioid use. Stefan Trapp, PhD, from University College London, explains that these drugs impact brain circuits involved in appetite and addiction.
Less Liver Trouble
Excess weight often leads to liver fat accumulation, causing silent inflammation and potential liver failure. Weight loss, particularly more than 10 percent, significantly reduces liver fat. Titchenell notes that GLP-1s may outperform other diabetes drugs in managing liver fat. Wegovy is now FDA-approved for managing liver fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD).
Lower Blood Sugar Levels
Originally developed as diabetes medications, GLP-1s effectively lower blood sugar and A1C levels, reducing the risk of diabetes complications. Layla Abushamat, MD, MPH, from Baylor College of Medicine, emphasizes the reduced risk of kidney complications and nerve issues associated with lower A1C levels.
As GLP-1 drugs continue to evolve, understanding their comprehensive effects is essential for users and healthcare providers alike. While they offer significant benefits, being aware of potential side effects ensures informed decision-making and optimal health outcomes.
