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TL;DR
Most of the side effects you’re going to read about online are real, mostly mild, and mostly settle within the first few weeks. A smaller group are worth understanding properly before you start — gallbladder issues, slowed stomach emptying that matters around surgery, hair shedding that recovers, and a few specific things to watch for. This article walks you through each one in plain English, tells you what the trials actually found, and tells you what to do about each. Where the evidence is thin, you’ll see that too. Where the South African regulatory picture matters — and it does — it’s spelled out.
GLP-1 (glucagon-like peptide-1) is a hormone your gut releases after meals. It tells your stomach to empty more slowly, signals “you’ve had enough” to a part of your brain called the area postrema, and helps your insulin response. The injections — Wegovy, Ozempic, Mounjaro — are synthetic versions of that hormone, dosed much higher and lasting much longer than your own body’s signal. Tirzepatide (the active ingredient in Mounjaro) does something similar at a second receptor as well, which is why it tends to produce a bit more weight loss.
Here’s the thing worth understanding upfront: the way these medicines work is also why most of the side effects happen. Slowing the stomach, dampening appetite, telling your brain you’re full — those aren’t separate from how the weight comes off. They’re the same mechanism. So when nausea shows up in week one, that isn’t the medicine going wrong. That’s the medicine working. The good news is, your body adjusts.
If you start a GLP-1 and feel queasy in the first week, you are not unusual. In the big trial of weekly semaglutide (the STEP 1 trial), about 44 in every 100 participants reported nausea, against 17 in every 100 on placebo [1]. With tirzepatide, the figures landed in a similar range across the doses [2]. With daily liraglutide, similar again [3].
What helps:
What’s reassuring: in the same trial, more than 95 in every 100 of these GI events were mild-to-moderate, and most settled within the first 4–8 weeks. About 4–5 in every 100 stopped the medicine because of GI side effects — meaningful but not the majority. If your nausea is still hitting you hard at month five, that’s a conversation with your prescriber, not something to grit your teeth through.
This sneaks up on people. About 24 in every 100 STEP 1 participants on semaglutide had it, against 11 on placebo [1]. The reason it happens is a combination — your gut moves slower on the medicine, you’re eating less (and often less fibre), and you might be drinking less water than you used to. All three add up.
What helps, in order of “try this first”:
Less common than the nausea but still real — about 31 in every 100 in STEP 1 had it, against 16 on placebo [1]. The mechanism isn’t fully worked out (probably bile-acid handling and gut transit changes), and it sometimes alternates with the constipation in the same person — confusing but normal. For most people, it settles within 8–12 weeks of being on a stable dose.
This is the side effect where the post-marketing data has overtaken the trial data. In a US claims-database study by Sodhi et al., people on semaglutide for weight loss had a markedly higher rate of gastroparesis (slow stomach emptying as a clinical syndrome) compared to a non-GLP-1 weight-loss option [4]. The absolute numbers are small, but the signal is real.
Here’s why it matters even if your stomach feels fine: in 2023, the American Society of Anesthesiologists put out guidance saying you should hold daily GLP-1s on the day of surgery, and weekly GLP-1s for a full week before any elective procedure. The reason is aspiration risk during anaesthesia — food sitting in a stomach that didn’t empty as expected can come back up while you’re under. From my plastic-surgery clinic specifically: please tell your surgical team you’re on a GLP-1, by name and dose, well before any procedure. Even something we’d consider a small day-procedure under sedation matters here.
This one is talked about less than it should be. STEP 1 showed cholelithiasis (gallstones) in roughly 2.6 in every 100 people on semaglutide vs 1.2 on placebo [1]. A 2022 meta-analysis pooling 76 trials and over 100,000 participants found GLP-1 medications increased gallbladder/biliary disease compared to placebo (about a third more events on average), with the risk highest at higher doses, longer use, and in weight-loss (rather than diabetes) settings [5].
Two things drive this. The first is the rate of weight loss itself — when you lose weight quickly, your bile gets more cholesterol-saturated, and that’s true of bariatric surgery and very-low-calorie diets too. The second is that GLP-1s themselves slow gallbladder motility a bit. The faster you lose, the higher the risk. Worth knowing about, not worth panicking over.
The headlines worry people more than the trial data justifies. Across STEP 1, SURMOUNT-1, SELECT, and the diabetes outcomes trial LEADER, there was no clear excess of acute pancreatitis on the medicine versus placebo [6]. The FDA’s labelling carries a (non-boxed) warning to stop the medicine if pancreatitis is confirmed. The most plausible biological pathway, given the gallbladder signal above, is that pancreatitis would more likely follow a gallstone than be caused by the medicine itself. If you’ve had pancreatitis before, this is a real conversation to have with your prescriber.
This one comes up a lot in our clinic. STEP 1 reported hair loss in about 3 in every 100 people on semaglutide vs 1 on placebo [1]. With tirzepatide, the figures sat around 5 in every 100 across doses [2]. Here’s the most important thing: this is not the medicine attacking your follicles. It’s telogen effluvium — the same diffuse shedding that happens after rapid weight loss of any kind, after pregnancy, after major illness, after bariatric surgery. Your hair cycle reacts to the body shifting fast.
It usually starts 2–4 months after you’ve started losing weight quickly (that delay is the hair-cycle catching up), and it almost always recovers within 6–12 months once weight stabilises and you’re eating enough protein and getting your micronutrients. It does not cause permanent or scarring loss. Biotin doesn’t have great evidence to back it up; making sure you’re hitting your protein and iron targets does.
This isn’t really a side effect of the medicine in the way the others are. It’s a side effect of the weight loss. The trials didn’t measure it, because facial volume isn’t a trial endpoint. But in my plastic-surgery practice this is one of the most common reasons GLP-1 patients walk through the door, so I want to spell out what’s actually happening.
In the order I usually see them deflate: the malar (cheek) compartment goes first and most visibly, then the buccal (lower cheek) and temporal (temple) compartments, and finally the perioral fat around the mouth. The changes typically become photographic at around 10% of body weight lost. The medicine itself doesn’t do anything to your skin — what it does is take away the fat support underneath, and what gets revealed is whatever skin laxity was already there. The gauntness reads as ageing because, in a sense, it is — the laxity was there before, the volume was just hiding it.
Two practical things follow. First, the change doesn’t fully reverse if you regain the weight — fat doesn’t always come back to the same compartments it left. Second, filler is not always the right answer. Over-volumising a face that has lost its structural fat can produce a swollen, unnatural look that ages worse, not better. Volumetric fat transfer, careful filler placed compartment by compartment, or simply slowing the rate of loss with adequate protein — all of these are options, and the right one depends on your face, your trajectory, and what you actually want. This is a discussion best had before you start, not after the fact.
When you lose a lot of weight quickly, some of what comes off is muscle. In the STEP 1 body-composition substudy, around 39% of total weight lost on semaglutide was lean mass — broadly the same proportion you’d lose with any non-medication weight-loss approach of similar speed [1]. This isn’t a GLP-1-specific problem; it’s a “losing weight quickly” problem.
What helps:
Most people have read the boxed FDA warning on these medicines and gotten alarmed. Here’s the honest picture. The warning rests on rodent studies — in rats and mice, GLP-1 agonism produces thyroid C-cell tumours [8]. Human C-cells have far fewer of these receptors and don’t respond the same way, which is the basis for the species-difference argument.
The human evidence is unsettled. One French claims-database study suggested elevated thyroid cancer risk with GLP-1 use [9]. A larger Scandinavian registry study published in BMJ in 2024 didn’t find an increased risk once you accounted for surveillance bias [10]. The pivotal weight-loss trials didn’t report any cases of medullary thyroid carcinoma. The conservative position — and the one your prescriber will take — is that personal or family history of medullary thyroid carcinoma, or of MEN-2 (multiple endocrine neoplasia type 2), is a contraindication. If that’s not your family history, the rodent-derived warning is real but the human-data signal isn’t there.
Most of what’s above is manageable. A small number of things aren’t, and they’re the ones to know by name before you start:
A short list of honest unknowns:
Three facts to hold in mind, because the picture in South Africa is different from what you’ll read on US blogs:
Wegovy (semaglutide 2.4 mg) is the only semaglutide registered with SAHPRA for weight management. Stock has been intermittent because of global supply pressure — check current availability with a South African pharmacy.
Ozempic and Mounjaro are registered with SAHPRA for type 2 diabetes only. Use for weight loss is off-label, which is legal under the supervision of a registered medical practitioner who is comfortable prescribing it that way — but it isn’t the same as a registered weight-loss indication.
Compounded semaglutide is not a registered medicine in South Africa. SAHPRA’s December 2023 communication was clear that compounding to get around supply or cost issues is not permitted under the Medicines Act, and the agency is on a Section 23 trajectory — the regulatory mechanism that lets it formally declare a practice “undesirable” and constrain it. What is permissible at the time of writing may not be permissible six months from now. Beyond the regulatory question, compounded products vary in provenance, sterility, and dose accuracy, and counterfeit semaglutide products have been seized internationally — including products labelled as semaglutide that contained no semaglutide at all. If you’re being offered a compounded product, ask your prescriber and the dispensing pharmacy for the registration status of what you’re being given.
The hard “no” list is short:
The “think harder before starting” list is longer: anyone over 65 who’s already lean to start with (the muscle-loss conversation matters most here), anyone with significant existing gastroparesis or unexplained chronic GI symptoms, anyone with an elective surgery looming in the immediate term, and anyone whose mental health is fragile right now.
A real consultation looks at the medicine in the context of your full history — medical, surgical, family, current medications, weight history, what you’ve tried before, and what you’re actually trying to achieve. It usually involves bloods and a clinical examination at baseline. It’s an honest conversation about what you can expect, what side effects to watch for given your starting profile, what these medicines cost (they’re expensive, and South African medical aids fund them in narrow ways — usually only via medical-savings or chronic-illness benefits, and mostly for diabetes), and what happens when you stop. It looks like a partnership, not a checkout flow.
If there’s one thing to take from all of this: the common side effects are real and mostly manageable, the less-common ones are worth understanding by name, and the South African regulatory picture for compounded products is actively shifting. A real consultation that knows your full history is materially safer than a website that doesn’t.
If you’ve read this far and are wondering whether a GLP-1 medication might be appropriate for your situation, the next step is a consultation with a registered medical practitioner — not adding something to a cart.
GLP-1 receptor agonists in the dosages, formulations and off-label uses discussed in this article are not, in those forms, SAHPRA-approved indications. We cannot comment on the safety, quality or efficacy of unregistered or off-label use in accordance with South African Health Products Regulatory Authority (SAHPRA) law. This article is for educational purposes only, does not constitute medical advice, and is not an advertisement for any specific compounded preparation. Any decision regarding treatment should be made in consultation with a registered medical practitioner. Where a compounded preparation is supplied through Dr Peptide, it is supplied only on the basis of an individual prescription written for a specific patient by a medical practitioner registered with the HPCSA and dispensed by a pharmacy registered with the SAPC.