Zepbound vs. compounded semaglutide for weight loss
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Found’s own Dr. Rekha Kumar explains the power of GLP-1s for weight loss, and how lifestyle changes are key to sustainability.
Even when you eat healthier and exercise more, losing weight—and keeping it off—can be challenging. Weight care can be much more complex than the simple calories in versus calories out equation. And according to the Obesity Action Coalition, obesity is not always a result of a poor diet and physical inactivity: Genetics, medications, and even certain diseases can cause obesity.
Some people struggling to get results or keep weight off are turning to prescription medications, including the GLP-1s (short for glucagon-like peptide-1 receptor agonists) that are flooding the news right now. And naturally, some are wondering whether they can forgo the lifestyle changes if they’ve got the drugs.
Rekha Kumar, MD, chief medical officer at Found and the former medical director of the American Board of Obesity Medicine, says behavior changes are important—not only for weight loss but also for long-term weight maintenance—for those taking GLP-1s. “Because of the excellent efficacy of GLP-1* medicines, some people might think behavior change is not as important,” she says. “But as time goes on—even on these new medicines—the body will fight back with increased hunger and metabolic slowing.”
Researchers explain this phenomenon with the set point weight theory, the idea that our bodies have a set point they want to maintain that prompts us to hold onto weight within a range when we start dropping pounds—intentionally or not. It’s thought of as the body’s natural survival mechanism to protect against starvation. This is why, Dr. Kumar says, “People will see better effects of the medication for longer if they can follow a diet and exercise plan.”
Researchers are still attempting to pinpoint precisely how GLP-1 medications work for weight loss. But what we do know from the literature is that these medications mimic a naturally occurring incretin hormone that’s released in your body after you eat. The hormone, GLP-1, slows gastric emptying to help you feel fuller, targets an area of your brain that can help reduce appetite and cravings, and helps to stabilize blood sugar—all of which may help with weight loss.
In one double-blind trial (meaning neither the participants nor the researchers knew which treatment participants were receiving), those given semaglutide, a GLP-1 medication commonly sold under the brand name Wegovy®, lost more weight. When combined with lifestyle changes (calorie restriction and exercise), those who received the GLP-1 medication lost an average of 15% of their body weight after 68 weeks. The other group, who made the same lifestyle changes and received a placebo, lost 2.4% of their body weight on average during that time.
Clinical trials studying the effectiveness of GLP-1 medications on weight loss encourage participants to make some lifestyle changes, dietary changes, or a combination of dietary and activity changes. So, we still don’t know whether GLP-1 medications alone can lead to clinically significant weight loss and weight maintenance.
And one study published in The New England Journal of Medicine showed that those who made lifestyle changes when taking a GLP-1 medication (liraglutide) for weight loss got better results. At the one-year mark, those who were prescribed exercise combined with the GLP-1 lost an average of about 21 pounds, compared to a nearly 15-pound average loss in the drug-only group, and about a 9-pound average loss in the exercise-only group. The body fat percentage of those in the exercise-plus-medication group decreased about twice as much as it did for those in the drug-only and exercise-only groups.
This is why many obesity medicine experts, including Dr. Kumar, consider lifestyle changes the cornerstone of lasting healthy weight loss and weight maintenance. Because factors like sleep, hydration, and stress can affect your weight independently, she says, “people will see better results in their weight loss and maintenance if they can adopt healthier habits overall.”
*Common side effects of GLP-1 medications include nausea, vomiting, diarrhea, and acid reflux. More serious but less common side effects include pancreatitis, gallbladder disease, and worsening of diabetic eye disease. Those with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasias should not use these drugs. Find detailed side effect and risk information for specific medications here.
About the writer, Morgan Pavon
Morgan Pavon, RD, is a registered dietitian and a former Found coach who writes about health and medicine at Found.
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