Conference Coverage

More STEP data: Semaglutide cuts weight, cravings, beats liraglutide


The STEP 5 clinical trial extends favorable weight loss from 1 year out to 2 years for the glucagon-like peptide-1 (GLP-1) agonist semaglutide (Wegovy, Novo Nordisk), given as a once-weekly 2.4-mg subcutaneous injection, and some food cravings were improved in a subgroup analysis.

In another study, STEP 8, weight loss was greater at 68 weeks with semaglutide subcutaneous injection than with a 3-mg daily subcutaneous injection of another GLP-1 agonist, liraglutide (Saxenda, Novo Nordisk), approved earlier for weight loss.

Researchers presented these promising outcomes, with no new safety signals, at ObesityWeek® 2021.

However, there is more to learn about the drug class, researchers agree. Follow-up is still relatively short for a chronic disease and many patients have gastrointestinal side effects with semaglutide, one expert cautions.

The key findings were:

In STEP 5, combined with lifestyle intervention (a reduced-calorie meal plan and advice about physical activity), weekly injection of 2.4 mg semaglutide led to:

  • 15.2% weight loss, compared with 2.6% weight loss with placebo at 2 years (P < .0001);
  • 77% of patients losing at least 5% of their weight, compared with 34% of patients in the placebo group at 2 years (P < .0001);
  • Significantly greater improvement in overall control of cravings, and craving for savory foods, in a subset of patients, versus placebo, but questionnaire scores for positive mood and craving for sweet foods were similar in both groups.
  • In STEP 8, mean body weight at 68 weeks was 15.8% lower with 2.4 mg/week subcutaneous semaglutide plus lifestyle changes versus 6.4% lower with 3.0 mg/day subcutaneous liraglutide plus lifestyle changes (P < .001).

Can treat to a target weight-loss range

The undiminished weight loss efficacy in the 2-year data for STEP 5 “portends well,” said W. Timothy Garvey, MD, following his presentation of the results.

Dr. W. Timothy Garvey, director of the diabetes research center at the University of Alabama at Birmingham

Dr. W. Timothy Garvey

“I think this is a new era in obesity care,” said Dr. Garvey, director of the diabetes research center at the University of Alabama at Birmingham. Semaglutide “essentially doubles weight loss efficacy” compared to the other approved pharmacotherapies for obesity.

With this degree of potential weight loss, clinicians “can use weight as a biomarker and treat to a target [weight-loss] range,” he said.

Expounding on this in an interview, Dr. Garvey noted that, as stated in the 2016 American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) clinical practice guidelines for medical care of patients with obesity, of which he was lead author, “the objective of care in obesity is to increase health of patients and prevent or treat complications.”

Semaglutide “can treat to a range of weight loss of 10% to 20% in the majority of patients,” which is associated with improvements in cardiovascular and metabolic risk factors.

In STEP 5, of the 51% of patients in the semaglutide group who had prediabetes at enrollment, 80% had normal glycemia at 2 years; however, the trial was not powered nor designed to investigate this.

More data are needed to inform long-term care decisions. The ongoing SELECT cardiovascular outcomes trial of semaglutide, with expected primary study completion on Sept. 28, 2023, should provide more information.


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