GLP-1 medication and perimenopause weight gain: what South African women need to know

The weight gain that happens in your forties does not feel like ordinary weight gain. The same eating habits, the same exercise routine, and suddenly things are different. Mostly around the middle. And mostly resistant to everything that worked before.

This is not a motivation problem. The hormonal shift of perimenopause changes how your body stores fat, burns calories, and regulates appetite at a biological level. GLP-1 medications, including semaglutide (sold as Ozempic and Wegovy) and tirzepatide (sold as Mounjaro), work at some of those same biological levers. This article covers what the evidence shows and what it means practically for women in South Africa right now.

What perimenopause actually does to your metabolism

Perimenopause starts, on average, in the mid-forties, though it can begin earlier. It is the years of hormonal fluctuation before your last period. Estrogen levels do not drop in a clean line; they fluctuate erratically before declining, and those fluctuations affect far more than the reproductive system.

Fat redistribution

Estradiol, the main form of estrogen during reproductive years, determines where your body prefers to store fat. While estradiol is present, fat tends to accumulate in the hips and thighs. As it declines, fat redistributes toward the abdomen and the visceral compartment, the fat that surrounds internal organs rather than sitting under the skin. Visceral fat drives insulin resistance, inflammation, and cardiovascular risk to a greater degree than subcutaneous fat.⁵

Research tracking women longitudinally through the menopause transition has found that visceral fat rises from roughly 5 to 8% of total body fat before menopause to 15 to 20% after it.⁴ This redistribution happens independently of whether total weight changes. The same number on the scale can represent a meaningfully different body composition by the time you reach postmenopause.

Metabolic rate and muscle mass

Estrogen receptors are present in muscle tissue and support muscle protein synthesis. As estradiol declines, lean mass loss accelerates. Because muscle is more metabolically active than fat, less muscle means a lower resting metabolic rate. Research has estimated that losing the luteal phase rise in energy expenditure alone accounts for roughly 100 kcal per day.⁴ Over months, that adds up without any change in what you eat.

Insulin sensitivity and appetite regulation

Estrogen helps maintain insulin sensitivity. Declining levels push many perimenopausal women toward a degree of insulin resistance, meaning the body has to produce more insulin to manage the same glucose load. Cortisol regulation is also affected; disrupted sleep from hot flushes and night sweats compounds abdominal fat storage. Appetite signals shift too. Hormonal fluctuations during perimenopause alter the signalling between the gut and the hypothalamus, the part of the brain responsible for hunger and satiety cues.

GLP-1 medications work precisely in that gut-to-brain channel.

How GLP-1 medications work

GLP-1 stands for glucagon-like peptide-1, a hormone your gut releases in response to eating. It signals the pancreas to release insulin, slows the rate at which food leaves the stomach, and tells the brain you have eaten enough. GLP-1 receptor agonists, including semaglutide (the active ingredient in Ozempic and Wegovy) and tirzepatide (the active ingredient in Mounjaro), mimic this hormone and extend its effect significantly longer than the natural version.

The result is a meaningful reduction in appetite and a reduction in how quickly hunger returns after meals. People on GLP-1 medication consistently report that food becomes less preoccupying and that smaller portions feel satisfying. The mechanism is hormonal, not willpower-dependent, which is why results are more reliable than lifestyle intervention alone.

In the STEP 1 trial, published in the New England Journal of Medicine in 2021, once-weekly semaglutide 2.4 mg produced mean body weight loss of 14.9% over 68 weeks, and 86% of participants achieved at least 5% weight loss.¹ The trial population was predominantly female, with a mean age in the mid-forties, meaning many participants were in or approaching perimenopause.

The evidence specific to perimenopausal and menopausal women

Most GLP-1 obesity trials have not stratified results by menopausal status, so the picture has been built from subgroup analyses and focused studies rather than dedicated perimenopause trials. That evidence is still useful.

Semaglutide and hormone therapy

The most cited study in this area was published in the journal Menopause in April 2024 by Hurtado and colleagues at Mayo Clinic.² The retrospective cohort study looked at 106 postmenopausal women with overweight or obesity treated with semaglutide; 16 were also on hormone therapy and 90 were not. Women on hormone therapy showed higher total body weight loss at every checkpoint measured: 3 months, 6 months, 9 months, and 12 months. At 12 months, the hormone therapy group had lost 16% of body weight compared to 12% in the semaglutide-only group. The hormone therapy group also had improvements in cholesterol and triglycerides that the semaglutide-only group did not show.

This was a retrospective study of 106 women, not a randomised controlled trial, and the hormone therapy arm was small at 16 participants. The authors called for larger studies to confirm the finding. But the direction of effect is consistent with the biology: hormone therapy attenuates visceral fat accumulation and preserves lean mass, while semaglutide acts on appetite and glucose regulation. The two are not doing the same thing, which may be why the combination outperforms either alone.

Why perimenopause specifically matters

Most published data, including the Hurtado study, focuses on postmenopausal women rather than perimenopausal women. Perimenopause, the transition period itself, has received less research attention despite being the phase when fat redistribution and metabolic changes are most actively occurring. Preliminary findings are consistent with GLP-1 medications being effective across the reproductive transition, but the field is still catching up with what women in their forties are asking.

What the existing evidence does support: the biological mechanisms behind perimenopause weight gain are real and well-documented, and GLP-1 medications address several of them directly. The appetite dysregulation, the insulin resistance component, and the visceral fat accumulation all respond to GLP-1 treatment in the broader evidence base.

What is available in South Africa right now

South Africa's GLP-1 landscape has changed substantially since 2024. Two products are the main options for women seeking treatment for weight management.

Wegovy (semaglutide)

Wegovy launched in South Africa in August 2025 and is the only GLP-1 product currently registered by SAHPRA specifically for weight management. It contains semaglutide at doses up to 2.4 mg weekly, the same dose used in the STEP 1 trial. Novo Nordisk reduced pricing significantly in early 2026; as of mid-2026, the starting dose sits around R1,873 per month and the maximum dose around R3,746. It is a Schedule 4 prescription medicine, available only through a registered SA doctor and a licensed pharmacy.

Ozempic (semaglutide, off-label)

Ozempic contains the same active ingredient as Wegovy but is registered in South Africa for type 2 diabetes, not obesity. Some doctors prescribe it off-label for weight management. The SA Ozempic pens go up to 1 mg, which is below the 2.4 mg dose used in obesity trials, so results are typically lower than what the Wegovy data shows. For women specifically asking about Ozempic for perimenopause weight gain: it is not the ideal first choice if Wegovy is accessible, but it is widely available and used in practice.

Mounjaro (tirzepatide)

Mounjaro, which contains tirzepatide, launched as a diabetes treatment via Aspen Pharmacare in December 2024 and received SAHPRA approval for weight management in October 2025. Tirzepatide targets both GLP-1 and GIP receptors. The SURMOUNT-1 trial showed mean weight loss of 20 to 22.5% at 72 weeks at higher doses.³ A 2025 post-hoc analysis looking specifically at postmenopausal women showed 23% weight loss versus 3% on placebo, and a 20 cm waist reduction versus 4 cm. Typical monthly costs at maintenance doses run R3,000 to R5,000 or above depending on dose.

A note on compounded products

Compounded semaglutide products are circulating in South Africa. They are not the same thing as the registered medicines. SAHPRA has warned repeatedly about falsified and compounded GLP-1 products sold through unregulated channels. Salt forms of semaglutide used by many compounders are not the registered active ingredient and have not been evaluated for safety or effectiveness. Use only products dispensed through a licensed pharmacy on a valid prescription from a registered SA doctor.

Common questions

Will GLP-1 medication work differently because of perimenopause?

The available evidence says not meaningfully. A 2025 analysis of the SURMOUNT trial across reproductive stages found no clinically significant differences in tirzepatide's effectiveness between premenopausal and postmenopausal women. Perimenopause changes where weight sits and why it accumulated, but it does not appear to blunt the GLP-1 mechanism.

Should I be on hormone therapy at the same time?

The Hurtado data suggests the combination improves outcomes, but hormone therapy eligibility depends on your individual medical history, symptoms, and clinical picture. That assessment belongs with a doctor experienced in menopause management. What the data does say is that if you are already on hormone therapy and considering GLP-1 medication, there is no indication of interference and potentially additive benefit. Both conversations are worth having with the right clinicians.

What about muscle loss on GLP-1 medication during perimenopause?

Losing weight on any approach involves some loss of lean mass alongside fat. This is a real consideration on GLP-1 medication, particularly for women in perimenopause who are already losing muscle mass due to declining estrogen. Adequate protein intake and resistance training are part of the protocol, not optional extras. A dietitian working alongside a prescribing doctor will structure a nutrition plan that prioritises protein targets and preserving functional muscle throughout treatment.

How long does it take?

Clinical trials measured primary outcomes at 68 to 72 weeks. Most people notice appetite changes within the first few weeks. Visible weight change usually starts between weeks 4 and 8. The results the STEP and SURMOUNT trials reported took 12 to 18 months to reach. GLP-1 medication is treatment for a chronic condition, not a short-term course.

Is Ozempic available in South Africa for perimenopause weight gain?

Ozempic is registered in South Africa for type 2 diabetes, not for obesity, though some doctors prescribe it off-label for weight management. Wegovy, which delivers semaglutide at the full weight-management dose of up to 2.4 mg weekly, is the registered option for weight loss and launched here in August 2025. Both require a prescription from a registered South African doctor.

For a full breakdown of costs, access, and how each product compares, see our companion article: How much does GLP-1 medication cost in South Africa?

References

1. Wilding, J.P.H., Batterham, R.L., Calanna, S., et al. (2021) 'Once-weekly semaglutide in adults with overweight or obesity (STEP 1)', New England Journal of Medicine, 384(11), pp. 989-1002.
2. Hurtado, M.D., Tama, E., Fansa, S., Ghusn, W., Anazco, D., Acosta, A., Faubion, S.S. and Shufelt, C.L. (2024) 'Weight loss response to semaglutide in postmenopausal women with and without hormone therapy use', Menopause, 31(4), pp. 266-274.
3. 'Once-weekly tirzepatide in adults with obesity or overweight (SURMOUNT-1)' (2022) New England Journal of Medicine, 387(3), pp. 205-216.
4. Thurston, R.C., Ewing, L.J., Low, C.A., Christie, A.J. and Levine, M.D. (2009) 'Increased visceral fat and decreased energy expenditure during the menopausal transition', International Journal of Obesity, 33(5), pp. 539-544.
5. Davis, S.R., Castelo-Branco, C., Chedraui, P., et al. (2012) 'Understanding weight gain at menopause', Climacteric, 15(5), pp. 419-429.