Blocking GLP-1 shows mixed results in weight loss

One study found that 55% of obese people regained the weight they lost after stopping GLP-1 medication, and so did 45% of diabetics. It also found that 45% of obese participants and 56% of diabetics lost weight or kept it off while off the medication.

However, many of those who had successful outcomes still received some form of treatment, as some of these participants simply switched between GLP-1 drugs. The study results did not take into account whether patients were still receiving treatment.

The research team, which led the study at the Cleveland Clinic in the US, says it is “one of the largest real-world studies to date.”

Hamlet Gasoyan, a researcher at the Cleveland Clinic Center for Value-Based Care Research who led the study, says: “Our real-world data show that many patients who stop semaglutide or terzapatide, restart the drug or switch to another obesity treatment, which may explain why they gain less weight than patients in the randomized trial.”

Changing treatment

The study, published in Diabetes, obesity and metabolismIt included 7,938 patients who were prescribed semaglutide or terzapatide between January 1, 2021, and December 31, 2023, and discontinued use after three to 12 months.

One year after discontinuation, 35.2% of patients received alternative obesity treatment.After one year of discontinuation, 35.2% of patients (2,794) received alternative obesity treatment: 27.4% received other medications, 13.7% received modifications and visits with a health care professional, and 0.6% received metabolic or bariatric surgery.

Meanwhile, 19.6% resumed the same medication. Switching between drugs was also common, as 16.1% switched from terzapatide to semaglutide, and 18.6% from semaglutide to semaglutide.

The study did not differentiate between participants who lost weight and those who did not.

“Many patients don’t give up on their obesity treatment journey, even if they need to stop their primary medications,” Gusoyan says. “In our future work, we will examine the comparative effectiveness of alternative treatment options for obesity in patients stopping semaglutide or terzapatide, to help patients and their clinicians make informed decisions.”

In the obese group, the average body weight lost before discontinuation was 8.4%, with a regain of 0.5% after one year. In the diabetic group, an average of 4.4% of body weight was lost before stopping, and 1.3% of body weight was lost one year later, the study reports.

Constraints and market gaps

The study did not distinguish how much weight was regained among those who stopped or continued treatment.

The study did not distinguish how much weight was regained among those who stopped or continued treatment.To address many of the study’s limitations, future research should examine the comparative effectiveness of treatments for obesity in patients who discontinue their novel GLP-1 receptor agonist (RA) or dual RA medications, the researchers conclude.

In a recent meta-analysis, UK researchers found that patients who lost weight regained an average of 60% of their weight within a year of stopping GLP-1 drugs such as Ozempic and Vigovi. This study included a systematic review of the existing scientific literature and 48 relevant studies.

The author of the UK study said: “Drugs like Ozympic and Vigovi act like brakes on our appetite, we feel full sooner, which means we eat less and therefore lose weight. When people stop taking them, they essentially take their foot off the brake and this can lead to rapid weight regain.”

Additionally, as these weight loss drugs interfere with hunger symptoms, they lead users to eat less overall. This has led experts to call for nutritional guidelines to prevent micronutrient deficiencies, loss of lean muscle mass, and other potential long-term health effects. This need has also encouraged the industry to innovate in products to fill the nutritional gap.

Startups and established companies are developing products to enhance the effectiveness of these drugs and manage their side effects, such as gut health and reduced appetite, to support overall metabolic health.