GLP-1 medications have moved from diabetes treatment to one of the most discussed topics in medicine in just a few years. The conversation around them is often dominated by either uncritical enthusiasm or reflexive dismissal, and neither serves women who are trying to make informed decisions about their own health.
For women in perimenopause and menopause, the context matters in specific ways. The hormonal changes of midlife create a weight management environment that is genuinely different from earlier decades, and understanding how GLP-1 medications interact with that environment is worth doing carefully.
This article covers the evidence honestly: what these medications do, what the research shows about effectiveness and safety, what the specific considerations are for midlife women, and what they cannot do on their own.
GLP-1 stands for glucagon-like peptide-1, a hormone naturally produced in the gut in response to food intake. It has several physiological roles: it stimulates insulin secretion in a glucose-dependent manner, suppresses glucagon (which would otherwise raise blood glucose), slows gastric emptying, and acts on receptors in the brain to reduce appetite.
GLP-1 receptor agonists are medications that mimic or enhance this hormone's effects. The two currently most relevant for weight management in non-diabetic adults are semaglutide (the active ingredient in Ozempic and Wegovy) and tirzepatide (the active ingredient in Mounjaro and Zepbound). Tirzepatide is a dual agonist, acting on both GLP-1 and GIP receptors, which produces somewhat greater weight loss in clinical trials.
Both are available as weekly injections. Oral semaglutide is also available, with lower bioavailability but meaningful efficacy for many patients. Both injectable forms have compounded versions available through licensed compounding pharmacies.
Compounded semaglutide and tirzepatide are not FDA-approved versions of these medications. Compounded medications are prepared by licensed pharmacies and have not been evaluated by the FDA for safety, efficacy, or quality. They may be an appropriate option for some patients under clinical supervision, but this distinction is important and should be part of any clinical conversation about these medications.
The STEP trial program evaluated once-weekly injectable semaglutide 2.4mg in adults with obesity or overweight with at least one weight-related comorbidity. The flagship STEP 1 trial found that participants lost an average of 14.9 percent of body weight over 68 weeks, compared to 2.4 percent in the placebo group.
A subsequent trial, STEP 5, extended follow-up to two years and showed that weight loss was sustained with continued treatment, with an average 15.2 percent reduction in body weight at 104 weeks.
The SURMOUNT trial program evaluated tirzepatide in adults with obesity. SURMOUNT-1 found average weight loss of 20.9 percent at the highest dose (15mg) over 72 weeks, making it the most effective approved medication for weight loss to date.
This is an important and often underdiscussed aspect of GLP-1 therapy. When medication is discontinued, the majority of lost weight is typically regained within one to two years. This is consistent with how the body treats any effective obesity treatment, including bariatric surgery, where weight regain is common if behavior change is not maintained.
The implication is that GLP-1 medications are most appropriately understood as a long-term treatment for a chronic condition, rather than a course of medication with a defined end point. This is a conversation worth having with a clinician before starting, not after.
The research on GLP-1 medications has generally been conducted in mixed adult populations. The specific hormonal context of perimenopause and menopause introduces considerations that are worth understanding.
Perimenopause is associated with significant metabolic changes including declining insulin sensitivity, increased visceral fat accumulation, and a shift in energy balance that makes weight gain easier and loss harder, even when behavior is unchanged. These changes are driven substantially by declining estrogen, which influences fat distribution, glucose metabolism, and energy regulation.
GLP-1 medications address the appetite and caloric intake side of this equation effectively. They do not directly address the hormonal drivers of metabolic change. This is why the combination of effective symptom management, including hormonal treatment where appropriate, with GLP-1 therapy tends to produce better outcomes than either alone for women in this life stage.
As discussed in depth in our article on strength training, muscle mass declines accelerate during the menopause transition. GLP-1 medications produce significant caloric restriction, which without a counterbalancing strategy will lead to loss of both fat and muscle.
Studies on GLP-1 medications have found that lean mass loss can represent 25 to 40 percent of total weight loss in the absence of resistance training. For midlife women already contending with sarcopenia risk, this is a meaningful concern. Resistance training and adequate protein intake are not optional add-ons to a GLP-1 program. They are essential components of it.
Emerging research has raised questions about bone density in the context of rapid weight loss on GLP-1 medications, particularly in populations already at risk for osteoporosis.9 The mechanism is not fully established, but is thought to involve reduced mechanical loading as body weight decreases, as well as potential direct effects of GLP-1 receptor activation on bone metabolism.
For postmenopausal women, who are already at elevated fracture risk, this is worth monitoring. Resistance training, which provides direct mechanical loading to bone, is one of the most effective interventions for maintaining bone density during weight loss.
The most common side effects of GLP-1 medications are gastrointestinal: nausea, vomiting, diarrhoea, and constipation.3 These are typically most pronounced during dose escalation and improve significantly for most people after the first four to eight weeks.
Practical strategies that help with initial gastrointestinal side effects include taking the injection at bedtime rather than in the morning, eating smaller and slower meals, avoiding high-fat foods during dose escalation, and ensuring adequate hydration.
GLP-1 medications are typically considered for adults with a BMI of 30 or above, or a BMI of 27 or above with at least one weight-related health condition such as hypertension, type 2 diabetes, or dyslipidaemia.10
For midlife women specifically, additional relevant indicators include:
Contraindications include pregnancy, personal or family history of medullary thyroid carcinoma or MEN2, personal history of pancreatitis, and severe gastrointestinal disease. A thorough clinical evaluation before starting is essential.
Being clear about the limits of these medications is as important as understanding their benefits.
GLP-1 medications are a genuinely effective tool. For the right woman, with the right clinical oversight and the right supporting strategies, they can produce meaningful and health-improving outcomes. Understanding what they do and do not do is the foundation of using them well.
Sources:
Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity.New England Journal of Medicine. 2022.
Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity.New England Journal of Medicine. 2021.
Garvey WT, Batterham RL, Bhatta M, et al. Two-year effects of semaglutide in adults with overweight or obesity (STEP 5 trial).Nature Medicine. 2022.
Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: STEP 1 trial extension.Diabetes, Obesity and Metabolism. 2022.
Lim J, Henry CJ, Sequeira IR. Clinical evidence for the disproportionate loss of lean mass during intentional weight loss.Journal of the Academy of Nutrition and Dietetics. 2013.
Soleymani T, Daniel S, Garvey WT. Weight maintenance: challenges, tools and strategies for primary care physicians.Obesity Reviews. 2016.
Wharton S, Calanna S, Davies M, et al. Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity.Diabetes, Obesity and Metabolism. 2022.
This article is for informational purposes only and is not medical advice. Always consult a qualified clinician to discuss your health and treatment options.
Hemma Wellness is not a medical practice. All clinical services are provided by licensed healthcare professionals through our partner network. Individual results may vary.
These statements have not been evaluated by the Food and Drug Administration. Compounded medications have not been evaluated or approved by the FDA for safety, efficacy, or quality. This content is intended for informational purposes only and does not constitute medical advice.
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