A new analysis of SURMOUNT-1, the first Phase 3 study of tirzepatide in adults for chronic weight management shows that tirzepatide improves body composition across a range of adult age groups. The analysis is presented by Dr Louis Aronne, Comprehensive Weight Control Center, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine, New York, USA, and colleagues.

The efficacy and safety of tirzepatide, a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, in people with obesity was investigated in SURMOUNT-1, the complete trial for which was published in NEJM in July 2022.

GIP and GLP-1 are hormones that are involved in blood sugar control and body weight regulation. After a person has eaten, these hormones are secreted by cells of the intestines and in turn cause the secretion of insulin. Tirzepatide activates both the GLP-1 and GIP receptors, leading to improved blood sugar control and enhanced satiety.

Tirzepatide is approved in the USA and the European Union to treat type 2 diabetes, but is not yet approved for obesity treatment in any country. The manufacturer of tirzepatide, Eli Lilly and Company, intends to seek approval for the drug as an obesity treatment from the US Food and Drug Administration (FDA), the European Union, and other territories beginning in 2023.

In this phase 3, double-blind, randomized, controlled trial, 2539 adults with BMI of 30 kg/m² or higher (with obesity), or 27 to 30 kg/m² (with overweight) with at least one weight-related complication, excluding diabetes, were assigned to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks. The percent change from baseline body weight and proportion of participants with body weight reduction of at least 5% were assessed across BMI categories: 27 to <30 (overweight), 30 to 35 (Class 1 obesity), 35 to 40 (Class 2 obesity), and 40 kg/m² and over (Class 3 obesity).

Body composition was evaluated in a subpopulation that underwent dual-energy x-ray absorptiometry. This new post-study analysis assessed change from baseline body composition within age subgroups under 50 years (n=99), 50 to 64.9 years (n=41), and 65 years and older (n=20).

Fat mass was reduced 33-36% and lean mass 10-11% depending upon age group. Thus, only one-quarter of the weight lost was lean mass, as has been observed in trials of diet and physical activity, resulting in an overall improvement in body composition. Across the age subgroups (under 50 years, 50 to 64.9 years, and 65 years and over), the change was almost identical, indicating no evidence of excess lean mass loss in older age groups.

The other published results from SURMOUNT-1 can be seen in the abstract link below and the full paper published in NEJM.

The authors conclude: "In this 72-week trial in participants with obesity, tirzepatide once weekly provided substantial reductions in body weight, consistent across all BMI categories, with improvement in body composition that was clinically meaningful and consistent across age groups."

Obesity is a chronic disease, like diabetes, hypertension, and the many other illnesses caused by obesity. The fact that chronic treatment is required is not surprising, and should be expected. It is relevant to understand the effect of weight loss on fat mass and lean mass, particularly in the elderly. This new analysis shows that around three quarters of the weight lost was fat mass, which is consistent across different ages."

Dr Louis Aronne, Comprehensive Weight Control Center, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine, New York, USA