The problem with the leaflet in the box is that it gives a heart attack and a burp the same visual weight. Everything is listed, nothing is ranked, and the reader is left to assume that anything printed is roughly as likely as anything else.
What people actually want to know is what will probably happen, what might happen, and what would need an ambulance. So that is the order.
Tier one: probable
You should expect at least one of these, and most people get several.
| Effect | STEP 1 rate | Placebo | What to do |
|---|---|---|---|
| Nausea | ~44% | ~17% | Smaller, cooler, lower-fat meals; it settles |
| Diarrhoea | ~30% | ~16% | Audit metformin, sweeteners, fibre |
| Vomiting | ~25% | ~7% | Hold the dose rather than escalating |
| Constipation | ~23% | ~10% | Fluid, psyllium, osmotic laxative |
| Abdominal pain | ~20% | ~10% | Distinguish from the pain that radiates to the back |
| Fatigue | ~11% | ~5% | Usually undereating, not the drug |
The placebo column is doing real work here. Roughly one in six people reported nausea while taking nothing at all, which is a useful corrective to the instinct to attribute every sensation of a given month to the injection.
Each of these has its own page: nausea, diarrhoea, constipation, and the full timeline in how long side effects last.
~44%
Nausea on semaglutide 2.4 mg in STEP 1 — against 17% on placebo
NEJM, 2021
Low single digits
Percentage who discontinued for gastrointestinal reasons in the pivotal trials
1 in 6
Placebo-arm participants who reported nausea while taking nothing at all
Tier two: possible
Common enough that you may well meet one, uncommon enough that most people do not.
- Reflux and heartburn — mechanical, and highly responsive to meal timing. See reflux on a GLP-1.
- Sulfur burps — more characteristic of tirzepatide. See sulfur burps.
- Injection site reactions — usually technique. See where to inject.
- Dizziness on standing — dehydration, or blood pressure medication that has become too strong for your new weight.
- Headache — very often fluid. See dehydration and your kidneys.
- Hair shedding — arrives two to four months after the fastest weight loss and regrows. See does Ozempic cause hair loss.
- Taste changes and food aversions — genuinely odd, generally transient.
- Disrupted sleep — usually reflux or nocturia rather than insomnia. See sleep on a GLP-1.
- Menstrual changes — a consequence of the weight loss working. See what happens to your cycle.
- Mood changes — real, under-studied, and not the thing the regulators investigated. See mood on a GLP-1.
Tier three: uncommon but serious
These are the ones worth being able to recognise. None is likely. All are actionable.
Acute pancreatitis. Severe, constant upper abdominal pain boring through to the back, eased by leaning forward, with persistent vomiting. Emergency department, same day. In the region of one to three cases per thousand patient-years. See pancreatitis on a GLP-1.
Gallbladder disease. Severe right upper abdominal pain after fatty meals, often radiating to the right shoulder blade. Roughly one additional case per seventy people treated. See gallstones on a GLP-1.
Acute kidney injury. Almost always the downstream result of vomiting or diarrhoea in someone who did not replace fluid — and far likelier if you take diuretics, ACE inhibitors, ARBs or SGLT2 inhibitors.
Ileus or bowel obstruction. No stool and no gas for days, with a distended, painful abdomen. Added to semaglutide labelling in 2023.
Severe hypoglycaemia. Only really a risk alongside insulin or a sulfonylurea, where doses need reducing when a GLP-1 is added. See drug interactions.
NAION — sudden painless vision loss in one eye. A genuine and unresolved signal. See the eye risk.
Tier four: the warnings that are not really about you
Thyroid C-cell tumours. A boxed warning derived from rodents, unconfirmed in humans over fifteen years. It reduces to one absolute rule: nobody with a personal or family history of medullary thyroid carcinoma, or with MEN2, takes these drugs. See the thyroid warning and the wider question in do these drugs cause cancer.
“Ozempic face” and loose skin. Not pharmacological side effects. These are what losing a fifth of your body weight looks like. See Ozempic face explained and loose skin after a GLP-1.
Muscle loss. Real, substantial, and largely preventable — which makes it the most important item on this page that most people never think of as a side effect at all. See the muscle question, protein and exercising on a GLP-1.
What actually helps, in order
- Hold the dose. Free, effective, and under-used.
- Change how you eat. Smaller, cooler, lower in fat, further from bedtime — what to eat on a GLP-1.
- Fix the fluid. Most headaches, fatigue and dizziness are water.
- Fix the technique. Room-temperature pen, ten-second hold, rotated site.
- Then reach for products. Tums or Gaviscon for breakthrough reflux, ondansetron — Zofran — on prescription for genuinely intractable nausea, and an osmotic laxative for constipation. Imodium has a place for short-term diarrhoea control, though not while there is fever or blood. The comparisons across the supplement category are in supplements for GLP-1 nausea and do you need supplements at all.
Almost nobody needs to stop this medication. A great many people need to spend eight weeks at a dose instead of four.
The number that gets left out
Discontinuation for gastrointestinal reasons in the pivotal trials ran in the low single-digit percentages.
That is the figure worth carrying. Side effects in this class are extremely common and very rarely decisive — which is a different sentence from the one most people take away from a leaflet, and a more accurate one.
If you are in week three
You are at the worst point of the schedule, reading a list of everything that could happen, having lost very little weight, on a starting dose that was never intended to produce any.
That is a bad week to make a judgement. The month-by-month version of what is coming is in the first eight weeks.