Which GLP-1 side effects are normal and which are not?
Written and medically reviewed by Zahraa Sater, M.D., M.P.H.
Reviewed August 12, 2026 · Next review due August 12, 2027
Short answer
Nausea, constipation, diarrhoea, burping and fatigue are expected on semaglutide and tirzepatide, are worst in the days after a dose increase, and usually settle. Severe abdominal pain radiating to the back, persistent vomiting, right upper abdominal pain with fever or yellow eyes, and signs of dehydration are not normal and need same-day assessment.
Get urgent care if:
- You have severe, persistent pain in the upper abdomen that radiates to your back, with or without vomiting
- You have pain under the right ribs with fever, chills, pale stools or yellowing of the eyes or skin
- You cannot keep fluids down for more than 24 hours, or you are passing very little urine
- You develop a rapid change in vision, particularly if you have diabetic retinopathy
- You have swelling of the face, lips or throat, or difficulty breathing
- You have new or worsening thoughts of harming yourself
Most GLP-1 side effects come from the same mechanism that makes the drug work: the stomach empties more slowly. That produces a predictable cluster of gut symptoms, worst in the first week after each dose increase, that fades as your body adapts. A smaller set of symptoms is not part of that pattern and should never be waited out.
What the trials actually recorded
On the Zepbound label, nausea occurred in 25 to 29 percent of patients, diarrhoea in 19 to 23 percent, constipation in 11 to 17 percent, vomiting in 8 to 13 percent, and abdominal pain in 9 to 10 percent. Hair thinning was reported in 4 to 5 percent. In STEP 1, 4.5 percent of the semaglutide group stopped the drug for gastrointestinal reasons, against 0.8 percent on placebo. In the head to head SURMOUNT-5 trial, 5.6 percent stopped semaglutide and 2.7 percent stopped tirzepatide for gut side effects. Most people do not stop.
The side effects that are expected
Nausea after the first injection at a new dose, early fullness, burping with a sulphurous taste, constipation that responds to fluid and fibre, loose stools after fatty meals, fatigue in the first fortnight, and mild injection site reactions are all within the expected range. Hair shedding two to four months into rapid weight loss is a telogen effluvium pattern driven by the rate of loss rather than by the drug itself, and it recovers. Reduced interest in alcohol is common and is not a problem.
The side effects that are not expected
Severe, constant upper abdominal pain that bores through to the back, with or without vomiting, is the pancreatitis pattern and is a same-day problem. Right upper abdominal pain after meals, fever, pale stools or yellowing of the eyes point at the gallbladder, and GLP-1 therapy raises gallbladder disease risk. Vomiting that stops you keeping fluids down can cause acute kidney injury through volume depletion, which is listed in the labels of both drugs. Sudden worsening of vision in someone with diabetic retinopathy, and new or worsening thoughts of self-harm, both appear in the warnings section and both warrant contact rather than observation.
Track two things in the first three months: your weight and the day of the week your symptoms peak relative to your injection. If symptoms are still severe more than a week after every dose increase, the answer is usually to hold the dose longer rather than to stop the drug. Take that pattern to your prescriber rather than adjusting on your own.
The clinical detail
Zepbound adverse reactions at 5 percent or greater: nausea 25 to 29 percent, diarrhoea 19 to 23 percent, constipation 11 to 17 percent, vomiting 8 to 13 percent, abdominal pain 9 to 10 percent, dyspepsia 9 to 10 percent, injection site reactions 6 to 8 percent, fatigue 5 to 7 percent, hypersensitivity 5 percent, hair loss 4 to 5 percent. Labelled warnings and precautions for both semaglutide and tirzepatide: thyroid C-cell tumours, acute pancreatitis, acute gallbladder disease, acute kidney injury from volume depletion, severe gastrointestinal reactions, hypersensitivity, hypoglycaemia with insulin or sulfonylureas, diabetic retinopathy complications, suicidal behaviour and ideation, and pulmonary aspiration during general anaesthesia. Escalation intervals are a minimum of four weeks per step for tirzepatide and four weeks per step for injectable semaglutide.
Written and medically reviewed by Zahraa Sater, M.D., M.P.H.
Reviewed August 12, 2026 · Next review due August 12, 2027
Sources
- ZEPBOUND (tirzepatide) injection, prescribing information, revised January 2026. U.S. Food and Drug Administration
- WEGOVY (semaglutide) injection, prescribing information. U.S. Food and Drug Administration
- STEP 1: Semaglutide Treatment Effect in People With Obesity. American College of Cardiology. PMID 33567185
- SURMOUNT-5: Greater Loss of Weight, Waist Circumference With Tirzepatide Than Semaglutide. American College of Cardiology. doi:10.1056/NEJMoa2416394
This library is educational and is not individual medical advice. Read our Editorial and Medical Review Policy.