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In a comparison of injectable GLP-1 receptor agonists, semaglutide (Wegovy) appeared to edge out liraglutide (Saxenda) when it came to weight loss, according to the phase IIIb STEP 8 study.

In a randomized trial of 2.4-mg semaglutide, 3.0-mg liraglutide, and matching placebo for both, those on semaglutide plus diet and exercise saw a 9.4% greater average loss in baseline weight compared with those on liraglutide, reported Domenica M. Rubino, MD, of the Washington Center for Weight Management and Research in Arlington, Virginia, and colleagues in .

Over the course of the 68-week trial, adults with overweight or obesity but without diabetes on semaglutide saw an average 15.8% weight loss versus 6.4% with liraglutide -- meeting the study's primary endpoint.

In addition, those on semaglutide had greater odds of achieving weight loss versus liraglutide, meeting confirmatory secondary endpoints (all P<0.001):

• 10% or more weight loss: achieved in 70.9% vs 25.6% of patients, respectively (OR 6.3, 95% CI 3.5-11.2)
• 15% or more: 55.6% vs 12% of patients (OR 7.9, 95% CI 4.1-15.4)
• 20% or more: 38.5% vs 6% of patients (OR 8.2, 95% CI 3.5-19.1)

On top of that, 27.6% of patients on liraglutide discontinued treatment for any reason compared with 13.5% on semaglutide. As expected with any GLP-1 receptor agonist, a large proportion of both treatment groups reported adverse gastrointestinal events.

Although both agents induce weight loss by reducing energy intake, Rubino's group pointed out the caloric intake reduction appears to be greater with semaglutide -- about 35% versus 16% with liraglutide.

"Semaglutide has also been associated with reductions in food cravings, which is less evident with liraglutide, suggesting different mechanisms of energy intake regulation," they wrote. "Further research is needed to investigate whether structural differences affect these mechanisms, for example, by allowing semaglutide to target a wider range of neuronal GLP-1 receptors than liraglutide."

This analysis was yet another installment in the Semaglutide Treatment Effect in People with Obesity (STEP) clinical program, which lent support for 2.4-mg semaglutide's FDA approval in June 2021. The agent was indicated for chronic weight management in adults with obesity (BMI of 30 or greater) or for adults with overweight (BMI 27 or greater) with at least one weight-related condition, such as high blood pressure, type 2 diabetes, or high cholesterol, used in conjunction with a reduced calorie diet and an exercise regimen.

Since its approval, 2.4-mg semaglutide found great success in the U.S. market, even to the point where demand exceeded supply. In late December, maker Novo Nordisk announced it was experiencing supply challenges, and said in part in a statement it "does not expect to be able to meet demand in the U.S. in the first half of 2022 and few new patients are expected to be able to initiate treatment."

Back in December 2014, 3.0-mg liraglutide was first approved for adults with a BMI of 30 or greater, or 27 or greater and at least one weight-related medical condition, in addition to lifestyle management. It was also approved in December 2020 for use in adolescents ages 12 to 17 with a body weight above 132 lb (60 kg) and obesity.

Both agents are also indicated at lower doses for patients with type 2 diabetes.

A total of 338 participants were included in this 19-site, open-label trial -- 126 received once-weekly subcutaneous semaglutide, with a 16-week escalation period, and 127 received once-daily subcutaneous liraglutide with a 4-week escalation phase. Those who couldn't tolerate 2.4 mg of semaglutide were eligible to receive 1.7 mg, and those who couldn't tolerate 3 mg of liraglutide could discontinue treatment and restart the titration.

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