Common GLP-1 weight loss drugs - including Wegovy and Ozempic - may not work for everyone in a “real-world” setting, Cleveland Clinic researchers said Tuesday.
The reason is that patients may take lower dosages or discontinue their treatment, negatively impacting the ability to control blood sugar levels in those who are pre-diabetic.
The findings may have implications for people considering using the drugs, that are taken by more than eight million Americans every year. They’ve offered an alternative to traditional and taxing weight loss methods, such as diets and fitness.
“Our study shows that patients treated for obesity with semaglutide or trizepatide lost less weight on average in a regular clinical setting compared to what is observed in randomized clinical trials,” Dr. Hamlet Gasoyan, a researcher with Cleveland Clinic, said in a statement. “According to our data, this could be explained by higher rates of discontinuation and lower maintenance dosages used in clinical practice, compared to randomized clinical trial settings.”
Gasoyan was the lead author of the study published on Tuesday in the Obesity Journal.
“Semaglutide has been extensively examined in robust clinical development programs, large real-world-evidence studies and has cumulatively over 33 million patient years of exposure,” a Novo Nordisk spokesperson told The Independent. “Semaglutide’s efficacy and safety have been extensively demonstrated in people with obesity/overweight with robust evidence for improving health outcomes. Semaglutide has demonstrated improvements in cardiovascular death, stroke, and myocardial infarction.”
A request for comment from Eli Lilly was not immediately returned to The Independent.
The study focuses on drugs with the active ingredients semaglutide and tirzepatide; they include the U.S. Food and Drug-administration approved type 2 diabetes medications Zepbound and Mounjaro. The authors studied their effects on weight loss and blood sugar regulation in a real-world setting. They noted that previous randomized clinical trials have shown the efficacy of those medications.
The authors monitored the health of nearly 7,900 adults who were severely obese. Of those, more than 1,300 had pre-diabetes at the study’s start and were at a higher risk for developing type 2 diabetes: a chronic condition that affects a person’s ability to use insulin and keep blood sugar at normal levels. Participants took the shots between 2021 and 2023.
The researchers sorted patients who discontinued their obesity medications into two groups: those who did it within just three months and by three months to a year. The study’s follow-up period ended last December.
The most common reasoning for discontinuation of treatment in the real-world setting was due to the steep cost of the drugs and insurance, side effects and shortages. Notably, since the study’s, prices have started to fall.
Of the participants, more than 20 percent discontinued their medications early and 32 percent discontinued their medications late. Furthermore, the authors noted than more than 80 percent had been on the lower dosages needed to sustain a therapeutic effect. For semaglutide, that’s equal to or less than 1 milligram and equal to or less than 7.5 milligrams for tirzepatide.
Following a year of treatment, the average weight reduction was 3.6 percent among participants who discontinued their treatment early, compared to 6.8 percent for those who discontinued their treatment late. But, those who did not discontinue treatment and were on the highest dosages necessary lost the most weight, at up to 13.7 percent with semaglutide and 18 percent with tirzepatide.
Participants had higher odds of achieving 10 percent or greater weight reduction after one year of treatment if they did not discontinue their medications or did so late, were on the highest dosages needed for a therapeutic effect, received tirzepatide, and were women.
Tracking the maintenance of blood sugar levels in those with pre-diabetes, the researchers said just a third of those who discontinued their treatment early experienced normal blood sugar levels compared to 41 percent who discontinued their treatment late and 67.9 percent who did not discontinue treatment.
Lastly, the researchers observed that while patients who discontinued obesity medications lost significantly less weight compared to those who did not, their weight trajectories remained relatively stable. They said that would be the subject of additional research.
“Our findings about the real-world use patterns of these medications and associated clinical outcomes could inform the decisions of healthcare providers and their patients on the role of treatment discontinuation and maintenance dosage in achieving clinically meaningful weight reductions,” explained Gasoyan.
