Conference Coverage

Tirzepatide’s benefits expand: Lean mass up, serum lipids down


AT EASD 2022

– New insights into the benefits of treatment with the “twincretin” tirzepatide for people with overweight or obesity – with or without diabetes – come from new findings reported at the annual meeting of the European Association for the Study of Diabetes.

Additional results from the SURMOUNT-1 trial, which matched tirzepatide against placebo in people with overweight or obesity, provide further details on the favorable changes produced by 72 weeks of tirzepatide treatment on outcomes that included fat and lean mass, insulin sensitivity, and patient-reported outcomes related to functional health and well being, reported Ania M. Jastreboff, MD, PhD.

Dr. Ania M. Jastreboff, Yale Medicine, New Haven, Conn. Mitchel L. Zoler/MDedge News

Dr. Ania M. Jastreboff

And results from a meta-analysis of six trials that compared tirzepatide (Mounjaro) against several different comparators in patients with type 2 diabetes further confirm the drug’s ability to reliably produce positive changes in blood lipids, especially by significantly lowering levels of triglycerides, LDL cholesterol, and very LDL (VLDL) cholesterol, said Thomas Karagiannis, MD, PhD, in a separate report at the meeting.

Tirzepatide works as an agonist on receptors for both the glucagonlike peptide–1 (GLP-1), and for the glucose-dependent insulinotropic polypeptide, and received Food and Drug Administration approval for treating people with type 2 diabetes in May 2022. On the basis of results from SURMOUNT-1, the FDA on Oct. 6 granted tirzepatide fast-track designation for a proposed labeling of the agent for treating people with overweight or obesity. This FDA decision will likely remain pending at least until results from a second trial in people with overweight or obesity but without diabetes, SURMOUNT-2, become available in 2023.

SURMOUNT-1 randomized 2,539 people with obesity or overweight and at least one weight-related complication to a weekly injection of tirzepatide or placebo for 72 weeks. The study’s primary efficacy endpoints were the average reduction in weight from baseline, and the percentage of people in each treatment arm achieving weight loss of at least 5% from baseline.

For both endpoints, the outcomes with tirzepatide significantly surpassed placebo effects. Average weight loss ranged from 15%-21% from baseline, depending on dose, compared with 3% on placebo. The rate of participants with at least a 5% weight loss ranged from 85% to 91%, compared with 35% with placebo, as reported in July 2022 in the New England Journal of Medicine.


Cutting fat mass, boosting lean mass

New results from the trial reported by Dr. Jastreboff included a cut in fat mass from 46.2% of total body mass at baseline to 38.5% after 72 weeks, compared with a change from 46.8% at baseline to 44.7% after 72 weeks in the placebo group. Concurrently, lean mass increased with tirzepatide treatment from 51.0% at baseline to 58.1% after 72 weeks.

Participants who received tirzepatide, compared with those who received placebo, had “proportionately greater decrease in fat mass and proportionately greater increase in lean mass” compared with those who received placebo, said Dr. Jastreboff, an endocrinologist and obesity medicine specialist with Yale Medicine in New Haven, Conn. “I was impressed by the amount of visceral fat lost.”

These effects translated into a significant reduction in fat mass-to-lean mass ratio among the people treated with tirzepatide, with the greatest reduction in those who lost at least 15% of their starting weight. In that subgroup the fat-to-lean mass ratio dropped from 0.94 at baseline to 0.64 after 72 weeks of treatment, she said.


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