Semaglutide outperforms liraglutide for long-term weight loss

A new study has found that people with obesity or type 2 diabetes (T2D) lost more weight after one year of medication with semaglutide than with liraglutide.

Cleveland Clinic researchers looked at the records of 3,389 obese adult patients who were prescribed either glucagon-like peptide 1 (GLP-1) drugs to treat type 2 diabetes or obesity between 2015 and 2022. They found that patients who took semaglutide or liraglutide to treat obesity were more likely to lose weight than patients prescribed drugs to treat type 2 diabetes, with semaglutide resulting in greater weight loss.

the studyPublication year JAMA Network OpenLead author Dr. Hamlet Gasoyan, a staff researcher in the Center for Value-Based Care Research, Department of Internal Medicine, Primary Care Institute, Cleveland Clinic, said the study identified “key characteristics that indicate the potential for achieving sustained weight loss of sufficient magnitude to provide clinically significant health benefits.”

After a year, only 40 percent of patients were still taking the medication, and those who didn't didn't achieve the same level of weight loss, Gasoyan said. Medscape Medical NewsIn a future paper, he and his colleagues plan to explore what causes patients to stop taking their medication.

Ghasoyan, an assistant professor of medicine at the Cleveland Clinic Lerner College of Medicine at Case Western Reserve University in Cleveland, said the results give patients and doctors reasonable expectations about weight-loss trajectories when prescribing drugs to treat diabetes and obesity.

Semaglutide Superior

Due to the time frame of the studies, the majority of GLP-1s were prescribed to treat type 2 diabetes: liraglutide was approved for the treatment of obesity in December 2020 (as Saxenda), and semaglutide was approved for the treatment of obesity in June 2021 (as Wegovy).

The authors were able to capture medication fills by brand name and dose approved by the U.S. Food and Drug Administration for the treatment of obesity (Wegovy, 1.7 or 2.4 mg; Saxenda, 3.0 mg) as well as brand names and doses approved for the treatment of type 2 diabetes (Ozempic, 0.5, 1.0, or 2.0 mg; Victoza, 1.2 or 1.8 mg).

The researchers reported that of 3389 patients, 1341 (39.6%) were prescribed semaglutide and 1444 (42.6%) were prescribed liraglutide for type 2 diabetes. For obesity, 227 (6.7%) were prescribed liraglutide and 377 (11.1%) were prescribed semaglutide.

Overall, the mean weight change for diabetic patients was -3.2%, while the mean weight change for obese patients was -5.9%.

Semaglutide consistently demonstrated superior efficacy to liraglutide, especially in obesity.

Overall, the mean weight change in obese people after one year was -5.1% with semaglutide compared with -2.2% with liraglutide (P < .001).

After one year, obese patients who continued to use semaglutide (defined as taking the medication for 90 to 275 days) had a mean weight loss of -12.9%, compared with -5.6% in patients taking liraglutide.

Overall, about 40% of patients had a sustained response at one year, but this figure was higher with semaglutide (45.8%) and lower with liraglutide (35.6%).

Liraglutide requires daily injections, whereas semaglutide requires weekly injections. The authors did not investigate adherence or reasons for discontinuation.

Key factors for achieving a weight loss of more than 10% that would be considered clinically meaningful included taking semaglutide, administering GLP-1 for obesity, continued use of the drug, high dose, and being female.

Real-world data welcomed

Michael Weintraub, M.D., an obesity medicine specialist and clinical assistant professor at NYU Langone Health in New York City, said real-world data on the effectiveness of GLP-1 is badly needed.

The researchers “did a very good job of stratifying these patients,” he said. Medscape Medical NewsHe added that the study “adds new information to the literature in terms of what to expect and what to look out for if you want to maximize your patients' weight loss and improve their overall metabolic health.”

One strength, he says, is that the researchers knew when prescriptions were actually filled: Clinicians don't always know whether GLP-1 prescriptions have been filled, he says, because insurance or supply issues can prevent patients from taking the drugs.

Weintraub wasn't surprised that the study showed that both GLP-1 and GLP-2 lead to more weight loss in obese people than in people with type 2 diabetes, because that's a common finding. Weintraub says no one can explain why there's such a difference. “The field really doesn't know yet why,” he says.

Given the small number of patients prescribed semaglutide to treat obesity, “generalizability is limited,” he said.

Still, semaglutide is proving to be increasingly better, Weintraub says. “I would definitely prescribe semaglutide for any patient with type 2 diabetes or obesity,” he says. “But the main limitation is insurance coverage, not my clinical judgment, unfortunately.”

He also thinks liraglutide could still be useful: It's coming off patent soon, which “could make it cheaper and more available to patients,” Weintraub said.

Gasoyan and Weintraub reported no relevant financial relationships. Co-author W. Scott Bucci, MD, reported receiving advisory board fees from Novo Nordisk A/S and research funding from Eli Lilly during the conduct of the study.

Alicia Ault is a freelance journalist based in St. Petersburg, Florida, whose work has appeared in publications such as: JAMA and Smithsonian.com. X: You can find me at @aliciaault.