Patients receiving semaglutide for weight loss show a significantly higher rate of continuing the medication at 1 year compared with less effective anti-obesity drugs. However, even among those patients, continuation declines to fewer than half of patients.
"We now have effective US Food and Drug Administration-approved anti-obesity medications; [however], this study shows that in a real-world setting, the vast majority of patients discontinued their prescription fills within the first year," said first author Hamlet Gasoyan, PhD, lead author of the study and a researcher with Cleveland Clinic’s Center for Value-Based Care Research, said in a press statement.
The study was published online today in the journal Obesity.
While breakthrough drugs such as glucagon-like peptide-1 (GLP-1) receptor agonists have shown high efficacy in achieving weight loss while providing a host of other health benefits, their discontinuation has been shown to potentially result in a rapid regaining of weight that was lost, as well as a reversal of the other health benefits, such as cardiometabolic improvements, the study authors wrote.
To evaluate rates of persistence with those along with other weight loss medications and factors associated with discontinuation, Gasoyan and colleagues conducted a retrospective cohort study, identifying 1911 patients with obesity, who had an initial anti-obesity medication prescription filled between 2015 and 2022 at Cleveland Clinic centers in Ohio and Florida.
Over the study period, 25% of patients filled a prescription for semaglutide, 34% for naltrexone-bupropion, 26% for phentermine-topiramate, 14% for liraglutide, and 0.9% for orlistat.
The patients had a median baseline BMI of 38, with obesity defined as a BMI of 30 or higher.
Medication Continuation Drops After 3 Months
With a median follow-up time of 2.4 years, the rate of persistence to the medications overall dropped from 44% at 3 months to 33% at 6 months and just 19% at 12 months.
In a multivariate analysis, semaglutide was associated with the highest odds of 1-year persistence (adjusted odds ratio [AOR], 4.26), while naltrexone-bupropion had the lowest odds (AOR, 0.68), compared with phentermine-topiramate. The other agents did not have significantly different odds of persistence.
Semaglutide and liraglutide also had the highest persistence rates overall, including at 3 months (63% and 52%, respectively) and 6 months (56% and 37%, respectively).
Those with higher weight loss at 6 months had a higher likelihood of remaining on the weight loss medication at 1 year, with a 1% increase in weight loss at 6 months associated with 6% increased odds of still being persistent at year 1 (adjusted odds ratio, 1.06).
Those who did continue medications at 1 year had a mean of 10% weight loss at 12 months compared with just 2% among individuals who were not persistent (P <.001).
Most patients (84%) in the study were privately insured, and weight loss drug adherence varied significantly based on the insurance carrier.
Studies demonstrating the effects of discontinuing treatment with semaglutide include the STEP 1 trial extension, which showed that 1 year after discontinuation of treatment and lifestyle intervention, participants regained two thirds of their lost weight on average, and the cardiometabolic improvements with the weight loss were reversed.
In light of those findings, "the current scientific knowledge favors using anti-obesity medications longer term for weight loss maintenance if they are well-tolerated and have resulted in clinically meaningful weight loss," Gasoyan told Medscape Medical News.
Paradoxically, the possible regaining of weight could be a factor in some insurers denying longer-term coverage, he noted.
Discontinuing Medications Means Regaining Appetite
Anne Peters, MD, a p rofessor of medicine at USC's Keck School of Medicine in Los Angeles and director of the USC Clinical Diabetes Programs, underscored that the possibility of regaining weight with discontinuation of GLP-1 receptor agonists is indeed "a big concern because your appetite comes back in spades when you take away the effect of these hormones," she told Medscape Medical News. "For that reason, I don’t ever tell people to stop cold turkey."
Regarding the question of how long patients should remain on the medications, Peters said the scenario might be compared to the need for patients with type 1 diabetes to be on insulin, which is a gut hormone.
"These medications are also gut hormones, and some patients may need to also be on them for life to maintain the benefits," she said.
"If a patient for some reason wishes to come off of the medication, for instance in order to be on less medicine, I have them titrate down and usually there will be a dose where they actually need only a small dose.
"I even have some patients who just take semaglutide once a month who are able to manage to maintain their weight loss," Peters noted.
"But the whole goal in people who are overweight or obese is to establish a new set point and maintain whatever that new target weight is."
Peters agreed that the loss of insurance coverage for the medications can throw a big wrench into that maintenance, presenting adverse effects of its own by causing a lack of treatment continuity.
"When you lose weight, you lose lean body mass and fat mass, but when you regain, it’s primary fat mass, so if you go on and off these drugs, it can contribute to a loss of lean mass. Therefore, these drugs should not be taken if someone is going to go on and off them repeatedly."
The study received funding from the National Cancer Institute. Peters has consulted for Eli Lilly in the past.
https://www.medscape.com/viewarticle/most-stop-taking-weight-loss-drugs-within-1-year-2023a1000uiq
