The Good and Bad Side Effects of Weight Loss Drugs

4 min read

GLP-1 DRUGS came to fame for their ability to help users take care of health conditions like diabetes and shed significant weight while minimizing “food noise.” But, as with many meds, this class involves all kinds of side effects—good and not-so-good—that may or may not strike the average user. Reminder that there are many of these meds now. GLP-1s currently used for weight loss—although not all are expressly approved for this purpose—include Ozempic and Wegovy (semaglutide); Victoza and Saxenda (liraglutide); and Mounjaro and Zepbound (tirzepatide), with more on the horizon, including retatrutide. Here’s what to look out for.

Muscle Loss

IF YOU DROP 15 to 25 percent of your body weight, 10 to 20 percent of that could be lean mass (muscle, bone, anything but fat). Still, that’s true of any type of weight loss, not just via these medications. Strength training helps counter that. In one study of people on liraglutide (Saxenda), those who lifted four times a week held on to muscle mass better than those who only took meds or only exercised. Also, “make sure your new diet is rich in muscle-building protein,” says Paul Titchenell, PhD, at the University of Pennsylvania.

ED

While the threat of this side effect gets tossed around, Jyotsna Ghosh, M.D., an obesity medicine physician at Johns Hopkins Medicine, says there’s not a lot of good data to support it. If anything, she says, the improved blood flow and inflammation should help your cause here. Wajahat Mehal, M.D., director of Yale Weight Loss Program, adds that by losing weight and improving conditions like diabetes in general, ED may naturally diminish as a result.

Queasiness

GLP-1s affect cells in a tiny V-shaped structure in your brain stem. This zone is a chemoreceptor—a spot that makes you feel like hurling when it meets something it doesn’t like, says Kevin Williams, PhD, at the University of Texas Southwestern Medical Center. That’s why nausea is the top side effect of GLP-1s, especially semaglutide. Meal timing can help; ask your doc for strategies.

Fortunately, tirzepatide comes with less severe and less prevalent digestive side effects—which may also include constipation—since it works on two receptors. “Tirzepetide is predominantly an agonist for the GIP receptor, and that pathway induces less nausea,” Dr. Mehal says.

Gallstones

These meds can slow the movement of bile—stuff produced by your liver to help with digestion—through your system. And any rapid weight loss alters its composition, allowing sandy deposits to form, says Dan Azagury, MD, a bariatric and minimally invasive surgeon at Stanford. That means a higher risk of gallstones, gallbladder inflammation, and bile duct problems, according to a review in JAMA Internal Medicine. Gallstones come with sudden, intense, worsening pain in your upper right belly, usually about a half hour to a few hours after you eat. Your move: Seek medical attention right away.

Sagging Skin

“Ozempic face” may sound scary, but sagging cheeks, deep wrinkles, and a lax jawline can happen with any rapid weight loss, says Patricia Mars, MD, a plastic surgeon in Tucson. The fibers that keep skin tight don’t rebound well after being severely stretched. Ask a dermatologist or facial plastic surgeon about topical vitamin C and retinoids, injectables, laser treatments, or surgery, says Clinton Humphrey, MD, a facial plastic surgeon at the University of Kansas Medical Center.

Fatigue and Loss of Pleasure

Dr. Ghosh says fatigue is one of the more common side effects patients talk about as well as anhedonia, or a loss of pleasure. These two side effects can comingle in the worst of ways, decreasing motivation to keep up an exercise habit. (Think: You’re tired and you don’t get the same workout high that you did in the past…) If you notice these effects, talk to your doctor about potentially switching up your dose or the type of medication you’re taking.

A Healthier Heart

PEOPLE TAKING GLP-1S have a reduced risk of heart attacks, strokes, and death from cardiovascular disease, according to a review in the Journal of Endocrinology. Credit not just the weight loss but also the drugs’ ability to reduce contributors to those conditions, including blood sugar, blood pressure, cholesterol, and inflammation.

This has been tested most rigorously for semaglutide, says Dr. Mehal; research found a 20 percent reduction in cardiovascular events (stroke and heart attacks) over a three-year period in a high-risk group. That does not mean everyone has a 20 percent reduction, but as a group, they do. Some might have an 80 percent reduction; others have none.

Fewer Cravings

GLP-1s quiet the urge to overeat and might also help you tackle issues like overdoing alcohol, smoking or vaping, and opioid overuse. “There is an overlap of brain circuitry used by appetite and by addiction to other things,” says Stefan Trapp, PhD, a professor of autonomic neuroscience and metabolic disease at University College London. The drugs are impinging on that system.

Less Liver Trouble

Extra pounds mean accumulated fat in your liver, which silently inflames it and can lead to liver failure. About 44 percent of men already have Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), says The Global NASH Council). Weight loss helps. With more than a 10 percent drop in weight, you have a dramatic reduction in liver fat, says Titchenell. GLP-1s may be better than other diabetes drugs at helping with liver fat, according to a study published in 2023. In fact, Wegovy is now FDA approved for managing liver fibrosis in people who have the liver disease known as MASH.

Lower Blood Sugar Levels

GLP-1s (you may remember) were developed as diabetes meds. So they lower your blood sugar and the telltale marker of how that sugar is doing over time, called A1C. Bonus: “By lowering your A1C, you also have a reduced risk for the complications from diabetes,” says Layla Abushamat, MD, MPH, an endocrinologist at Baylor College of Medicine. That means less risk of kidney complications that can put you on dialysis and of nerve issues that can lead to amputations.

Related Stories

Julie Stewart is a writer and content strategist whose work has also appeared in Health, and Women’s Health, Everyday Health, Vice, and Shape.

Caitlin is a health and fitness journalist based in New York City. She writes for publications including The Wall Street Journal and Runner’s World. She’s completed 12 marathons, including the six World Marathon Majors, is semi-fluent in French, and volunteers as a greeter on The High Line. Follow her on Instagram or LinkedIn.