Tirzepatide adds significant weight loss even after lifestyle changes
Presenter: Ariana Chao, PhD, RN, of Johns Hopkins University School of Nursing in Baltimore, MD
Chao AM, Wadden TA. SURMOUNT-3 efficacy results. Presentation at Obesity Week, October 14–17, 2023, Abstract Oral-038.
Treatment with tirzepatide leads to clinically meaningful additional body weight reductions in adults with overweight or obesity who had already lost weight with an intensive lifestyle intervention.
After losing at least 5% of body weight after 12 weeks of diet and exercise, patients who took the dual glucagon-like peptide 1 and gastric inhibitory polypeptide receptor agonist tirzepatide lost an additional 18.4% of weight, according to results from the phase 3 SURMOUNT-3 trial. In comparison to an average 2.5% increase weight in the placebo group, those on tirzepatide lost 20.8% more of their body weight over 72 weeks, said presenter Ariana Chao, PhD, RN, of Johns Hopkins University School of Nursing in Baltimore, MD, at the 2023 Obesity Week annual meeting.1
Study results were simultaneously published in Nature Medicine.2
Intensive lifestyle intervention is recommended as the cornerstone of obesity management, but fewer than 20% of patients treated with lifestyle interventions lose 15% or more of baseline weight. Also, patients often regain one-third of lost weight in the year following treatment, and increasingly regain weight over time.3,4
Earlier trials using tirzepatide found the drug helped people lose weight. In SURMOUNT-1, patients who took a 15-mg injection of tirzepatide showed a 17.8% difference in weight loss compared with a placebo group over 72 weeks.5 SURMOUNT-2 reported a 12.4% difference in body weight loss with the 15-mg dose versus placebo in people with obesity who had type 2 diabetes.6
In the double-blind, placebo-controlled SURMONT-3 trial,1,2 after the lifestyle intervention lead-in, 579 obese participants were randomized either to tirzepatide (287 participants) at the starting dose of 2.5 mg, which increased by 2.5 mg every 4 weeks until a maximum dose of 10 or 15 mg was reached, or to placebo (292 participants).
Most participants were white (86%) and female (62.9%), with an overall mean age of 45.6 years. The average duration of obesity was 15.1 years, and two-thirds had a medical history of 1 or more obesity-related complications. All participants had a body mass index of at least 30 kg/m2, or at least 27 kg/m2 along with 1 or more weight-related comorbidities, plus at least 1 unsuccessful attempt at weight loss through diet. Demographics and clinical characteristics were similar in both groups.
Tirzepatide substantially increased the amount of weight loss following the intensive lifestyle intervention, which had reduced baseline body weight by an average of 6.9%. In total, 87.5% of tirzepatide-treated participants lost an additional 5% or more of their randomization weight compared with 16.5% of placebo-treated participants. Body mass index dropped an average of 7.7 kg/m2 with tirzepatide vs a 1.2-kg/m2 rise with placebo.
“These findings indicate that individuals with overweight or obesity who have lost approximately 5% to 10% of their body weight with supervised lifestyle intervention—or potentially through their own self-directed diet and exercise efforts—could expect to achieve further clinically meaningful weight loss with the addition of tirzepatide,” the authors wrote.
The safety profile of tirzepatide was consistent with findings from previous trials for the treatment of obesity or type 2 diabetes. Mild-to-moderate gastrointestinal events were the most frequent treatment-emergent adverse events, and were mostly transient and occurred during dose escalation. The most common adverse events were gastrointestinal, including nausea (39.7% vs 14%), diarrhea (31% vs 9.2%), and constipation (23% vs 6.8%).
In addition to weight loss, significantly more participants on tirzepatide than placebo saw improvements in pre-specified endpoints, including cardiometabolic risk factors such as lipid parameters, blood pressure, and glycemic measures such as fasting glucose, fasting insulin, and hemoglobin A1c.
References
- Chao AM, Wadden TA. SURMOUNT-3 efficacy results. Presentation at Obesity Week, October 14–17, 2023, Abstract Oral-038.
- Wadden TA, Chao AM, Machineni S, et al. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nat Med 2023; 29(11):2909–2918. doi:10.1038/s41591-023-02597-w
- Heymsfield SB, Wadden TA. Mechanisms, pathophysiology, and management of obesity. N Engl J Med 2017; 376(3):254–266. doi:10.1056/NEJMra1514009
- Wadden TA, Tronieri JS, Butryn ML. Lifestyle modification approaches for the treatment of obesity in adults. Am Psychol 2020; 75(2):235–251. doi:10.1037/amp0000517
Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med 2022; 387(3):205–216. doi:10.1056/NEJMoa2206038
Garvey WT, Frias JP, Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 2023; 402(10402):613–626. doi:10.1016/S0140-6736(23)01200-X
Disclosures
Dr. Chao reports grants or contracts from National Institutes of Health, WW International, Inc, The Edna G. Kynett Memorial Foundation, Novo Nordisk and Epitomee Medical; consulting fees from Eli Lilly and Company and Boehringer Ingelheim; and payment or honoraria for presentation and travel/meeting support from the Obesity Medicine Association.