Semaglutide, sold under the brand names Ozempic and Rybelsus (an oral form of the medication), helped more than two-thirds of people with type 2 diabetes lose at least at least 5 percent of their weight in a 68-week clinical trial, according to the study results published in March 2021 in The Lancet. Almost half of the participants lost at least 10 percent of their weight, and roughly one-quarter of them lost at least 15 percent of their weight. “This is by far the best result we have had with any weight loss medicine in patients with diabetes,” says senior study author Ildiko Lingvay, MD, MPH, a professor and endocrinologist at the University of Texas UT Southwestern Medical Center in Dallas. “With this drug, results are getting close to what we see with bariatric surgery, which is 20 to 30 percent weight loss,” Dr. Lingvay says. RELATED: Can Weight Loss Surgery Reverse Type 2 Diabetes?
Semaglutide May Boost Effects of Diet and Exercise Changes to Increase Weight Loss
The trial enrolled 1,210 adults with type 2 diabetes and a body mass index (BMI) of 27 or higher. They all received counseling from a dietitian every four weeks, and they were all encouraged to get 150 minutes per week of exercise and to follow a diet designed to create a 500-calorie deficit each day. Each week, participants received injections with a placebo, a 1 mg dose of semaglutide that’s already approved to treat type 2 diabetes, or a 2.4 mg dose of semaglutide that the drug’s manufacturer Novo Nordisk has asked the U.S. Food and Drug Administration (FDA) to approve as a weight loss aid. By the end of the 68-week trial, people on 2.4 mg semaglutide lost 9.6 percent of their body weight on average, compared with an average weight loss of 7 percent on the 1 mg dose and 3.4 percent with the placebo. Because the weight loss achieved with placebo is assumed to stem from diet and exercise changes, as well as nutrition counseling, researchers estimated that high-dose semaglutide alone helped patients lose an average of 6.2 percent of their body weight. People on 2.4 mg semaglutide also had better blood sugar management by the end of the study, based on their A1C results, which show average blood sugar over around three months. At the end of the trial, participants on 2.4 mg semaglutide had average A1C readings of 6.4 percent — in the prediabetes range, which is below the threshold to diagnose type 2 diabetes — compared with 6.6 percent on 1 mg semaglutide and 7.8 percent on placebo. RELATED: The Prediabetes Diet Everyone Should Follow
Safety and Effectiveness of Weight Loss Drugs
The most common side effects with semaglutide were gastrointestinal issues including nausea, vomiting, diarrhea, and constipation, which 77 to 89 percent of participants in all three study groups reported. Many drugs that have been approved for weight loss in the past have been withdrawn due to serious and potentially life-threating side effects, according to an editorial published in February 2021 in The New England Journal of Medicine. These include several amphetamines that caused addiction; fenfluramine, which caused heart valve damage; and lorcaserin, which increased the risk of cancer. Semaglutide is in a family of medicines known as GLP1 agonists, which mimic the action of a hormone that causes people to feel full. A similar drug, liraglutide, is already approved for weight loss in people with type 2 diabetes. Several other medications approved for weight loss have not achieved results as dramatic as those seen with semaglutide in the current trial, according to a review of anti-obesity treatments published in January 2021 in Current Obesity Reports. To try to isolate the effect of weight loss drugs alone, researchers subtracted the weight lost in the placebo group, which only followed lifestyle interventions, from the amount of weight lost in the study group, which followed lifestyle interventions and took medication. They found that participants lost an average of 6.8 percent of their body weight with phentermine-topiramate, followed by 5.4 percent with liraglutide, 4 percent with naltrexone-bupropion, and 2.9 percent with orlistat.
Weight Loss Tends to Be Harder With Type 2 Diabetes
But many of these results were achieved in people without type 2 diabetes, who typically have an easier time losing weight than individuals with this metabolic disorder. In people without type 2 diabetes, a study published in February 2021 in The New England Journal of Medicine found people on semaglutide 2.4 mg lost an average of 12.4 percent of their body weight. “People with diabetes tend to lose less weight in clinical trials of anti-obesity drugs than people without obesity,” says Frank Greenway, MD, medical director at the Pennington Biomedical Research Center in Baton Rouge, Louisiana. “It is not entirely clear why diabetic individuals lose less weight than nondiabetics, but one possible explanation is that people with diabetes are often told by their physicians to lose weight so they will not go blind and lose their legs,” Dr. Greenway says. As a result, in an effort to help prevent these complications, people with diabetes (including those who partake in studies) may generally be more motivated to try to lose weight compared with people who do not have diabetes. This may mean that study participants with diabetes tend to be closer to their body weight set point (a weight range that the body fights to maintain) than study participants without the disease at the start of clinical trials. Yet the results of the current study do suggest that the higher dose of semaglutide may help people with type 2 diabetes lose more weight than they can taking the lower dose of the drug currently approved for diabetes, says Robert Kushner, MD, a professor of endocrinology at Northwestern University Feinberg School of Medicine in Chicago. RELATED: 7 Surprising Things That Affect Weight When You’re Managing Type 2 Diabetes
Long-Term Weight Management in Type 2 Diabetes
Lifestyle changes should be the first thing tried for weight loss, regardless of whether you have diabetes, says Lingvay. But efforts to eat less and exercise more often fall short of weight loss goals, or are unsustainable over time, Lingvay adds. “Additional interventions — either pharmacological or surgical — are needed for long term success,” Lingvay says. Not all people are candidates for surgery, however, and the decision to choose surgery or medication for weight loss is an individual one that you need to discuss with your doctor, says says Beverly Tchang, MD, an assistant professor at Weill Cornell Medicine in New York City. For people with diabetes, though, the results of the latest study suggest that it makes sense to consider semaglutide to manage blood sugar because it can also help with weight management, says Dr. Tchang. Many drugs other drugs approved for diabetes, including some forms of insulin, sulfonylureas, and thiazolidinediones (TZDs), have been linked to weight gain. “Given the choice between a diabetes medication that might cause weight gain versus a medication that might cause weight loss, I’d prefer the one that causes weight loss, and I think many patients would prefer the same,” Tchang says. RELATED: More Evidence Semaglutide Outperforms Liraglutide for Weight Loss
