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GLP-1 receptor agonists and dual GIP/GLP-1 agonists are among the most studied pharmacologic interventions in the history of obesity medicine. What follows is a summary of the primary trials and the mechanism relevant to women in perimenopause.
SURMOUNT-1 was a 72-week randomized controlled trial of tirzepatide in adults with obesity. Participants on the highest dose achieved a mean of 20.9% body weight loss. Secondary endpoints included improvements in waist circumference, blood pressure, and lipid parameters.
STEP-1 was a 68-week trial of semaglutide 2.4 mg once weekly. Participants achieved a mean of 14.9% body weight loss, with concurrent improvements in HbA1c in participants with pre-diabetes.
Estrogen decline in the perimenopausal transition alters fat distribution toward visceral deposition, reduces resting metabolic rate, and decreases insulin sensitivity. These are the biologic reasons diets that worked in a woman's 30s frequently stop working in her 40s.
The 24-Week Reset applies a titration roadmap from level 1 to level 5. Titration is individualized to tolerance and clinical response. Lab draws at baseline and month 3 monitor metabolic markers. Member Concierge sessions bi-weekly address side effects, adherence, and clothing-fit measures as proxies for body composition.
- 1. Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-216.
- 2. Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989-1002.
- 3. Mayo Clinic. Perimenopause and weight. 2025 clinical review (placeholder citation).
- 4. STEP-1, as cited above.
- 5. SURMOUNT-1, as cited above.