Where you carry your fat can dictate your cardiovascular age. (© Pixel-Shot - stock.adobe.com)
You know what they say about things that seem too good to be true. At first, it looked like permanent weight loss could be achieved using GLP-1 drugs like Ozempic or Mounjaro. People thought this was the case even after they stopped using these drugs, however, the results didn’t meet those expectations. Other than staying on the drug, there is no evidence that GLP-1 drugs maintain weight loss after patients discontinue their use. There’s also no evidence that strategies to prevent weight regain, like weaning yourself off the medication, helps maintain weight loss.
According to Nate Wood, MD, MHS, at the Yale School of Medicine, obesity is a chronic disease that requires chronic treatment. So far, clinical trials show that weight lost while using GLP-1 drugs is regained after discontinuing the drugs.
In one trial, called the Step 1 trial extension, 1,961 adults who were overweight or obese, but did not have diabetes, lost an average of 14.9% of their body weight over 16 months. Their results were compared to people taking a placebo, who lost 2.4% of their body weight.
Individuals in this trial who lost 17.3% of their body weight entered an extension phase of the trial. Patients stopped using the drug, semaglutide, as was lifestyle counseling. Stopping the drug was associated with a regain of 11.6% of the average participant’s original weight. That meant that about two years into the trial, net weight loss in the drug trial group was about 8.4 lbs. for the average 150 lb. person, or about 11.2 lbs. for a 200 lb. person.
John Wilding, DM, corresponding author for the extension arm of the trial, at Aintree University Hospital in the United Kingdom reported that the results were not a surprise. He compared the situation to high blood pressure and high cholesterol, both chronic diseases. When patients stop taking antihypertensive drugs or cholesterol-lowering drugs, blood pressure and blood cholesterol levels return to their former, higher numbers, and sometimes rising even higher. Wilding notes that obesity is no different.
Patients in another trial, the Step 4 Trial, lost 10.6 of their body weight over four months. These patients were randomized, either taking a maintenance dose of the drug or a placebo, but they also continued their lifestyle interventions.
Those on the drug for another 11 months continued their weight loss, roughly losing an additional 8%. Those switched to a placebo regained almost 7% of their original body weight they had lost.
Another trial, the Surmount-4 Trial, focused on withdrawal from tirzepatide (Zepbound), a combination of a GLP-1 agonist (booster) and an insulin agonist. After 36 weeks on the drug, patients had an average loss of almost 21% of their body weight. They were also randomized to either stay on the drug or start taking a placebo while continuing their lifestyle support. The patients who stayed on the drug lost additional weight. At the endpoint of the trial, they had lost just over 25% of their body weight.
Those who had been on the trial for 88 weeks were then switched to a placebo, leading to weight gain. The net loss was about 10% of their original body weight. Robert Kushner, MD, of the Northwestern University Feingold School of Medicine said this emphasizes the biological nature of the disease of obesity, and the importance of medications that manage the condition.
The challenges of long-term weight loss drug usage
In all these trials it is clear that continuing to take the drug helps to continue or maintain weight loss. Continuance of the drug, however, carries with it the challenges of any long-term drug. The medication must fit the individual’s lifestyle, including travel, switching pharmacies when moving, method of delivery, cost, and method of storage (such as refrigeration).
The side-effects of GLP-1 drugs may prove problematic to long-term use, since gastrointestinal side-effects are significant. Careful dose adjustments are needed to avoid weight loss that’s too rapid, which can predispose someone to complications such as gallstones or a loss of muscle mass.
Stopping the drug can also trigger mental health issues – including a resurgence of extreme cravings and an intense sense of starvation.
Tools to maintain weight loss
Right now, there is no specific data on strategies to maintain weight loss after using GLP-1 drugs. That’s among the top concerns of people who have or will stop drug treatment at some point in the management of their chronic disease.
What is apparent and supported by data is that stopping the medications abruptly is problematic. The studies cited in this article are examples of this – when stopping the drugs, doses were not tapered.
This may be why the art of medicine is key to weight-loss maintenance strategies. Every day, healthcare providers help patients make decisions influenced by the provider’s expertise, as well as evidence.
Long-term weight management calls for individualized discussions and creative solutions. Some potential strategies may include dose-tapering, intermittent therapy, using different, older drugs, or more intensive lifestyle modifications.
What should patients do?
If you are receiving GLP-1 treatment or considering treatment, keep seeing your prescribing doctor. Ask lots of questions. Engage in discussions. Present your own ideas and beliefs. Be honest with yourself about your willingness to commit to do what it takes to maintain or continue weight loss, even when you’re not taking these drug.
