Which Tirzepatide and Semaglutide Side Effects Are Serious?
If you are starting a GLP-1 weight loss medicine such as compounded tirzepatide or semaglutide, or thinking about it, side effects are a fair first question. Most are mild. Most get better if you keep taking the medicine.[3]
The most common tirzepatide side effects affect the stomach and bowel. These include nausea, diarrhea, vomiting and constipation. In the main trial, most were mild to moderate. They happened mainly while the dose was being raised.[1] For semaglutide, nausea and diarrhea are the most common. They are usually short-lived and mild to moderate.[2] Serious side effects are rare, but it helps to know them so you can act fast.
Common Side Effects
These are the side effects listed most often for both medicines:[4][5][6]
- nausea, vomiting, diarrhea or constipation
- stomach pain, heartburn or burping
- feeling tired
- redness or itching where you inject
- hair loss
Most people stay on treatment. In the semaglutide trial, 4.5% of people stopped because of stomach side effects. On a placebo (dummy shot), it was 0.8%.[2] In the tirzepatide trial, 4.3% to 7.1% stopped because of any side effect, by dose. On a placebo, it was 2.6%.[1]
Easing Nausea
Nausea is one of the most common side effects of both medicines.[1][2] In the tirzepatide trial, stomach side effects came mainly while the dose was going up.[1] That is one reason both medicines start low and go up in steps. Semaglutide is usually raised after 4 weeks, and tirzepatide no more often than every 4 weeks.[4][5]
Vomiting or diarrhea can leave you short of fluids, which can strain the kidneys, so keep drinking.[4] Clinicians usually try other steps first, such as lowering the dose, but a short course of an anti-nausea medicine is an option for some people.[10] You can request Zofran (ondansetron), a prescription tablet for nausea, through Starfish.com. If nausea is hard to manage, send us a message through your secure online account.
Treatment With a Clinician Reviewing Your Health
Answer a short questionnaire about your health and medicines. A licensed clinician reviews it before prescribing compounded tirzepatide or semaglutide.
What to Do About Serious Side Effects
Serious side effects are rare.[3][6] Each one has signs you can watch for.
| Side effect | Signs to watch for | What to do |
|---|---|---|
| Inflamed pancreas (pancreatitis) | Severe stomach pain that does not go away and may spread to your back[4][6] | Stop the medicine and get medical care right away |
| Gallbladder problems, including gallstones | Severe pain in the upper stomach, fever, yellow skin or eyes, or pale stools[4][6] | Get medical care right away |
| Low blood sugar | Sweating, shaking, dizziness, confusion or a fast heartbeat. More likely if you also take other diabetes medicines[6][7] | List every diabetes medicine in your questionnaire. Get medical care if symptoms do not settle quickly |
| Dehydration and kidney problems | Passing less urine, or swelling in your legs, after vomiting or diarrhea[4] | Drink fluids and get medical care if you cannot keep them down |
| Severe allergic reaction | Swelling of the face, tongue or throat, hives or trouble breathing[5] | Call 911 |
The Thyroid Warning
Both medicines caused thyroid tumors in rats. No one knows yet if they do the same in people.[4][5] So if you or a close relative has had a thyroid cancer called MTC, or a condition called MEN 2, you should not use them.[3]
See a doctor in person if you notice a lump or swelling in your neck, hoarseness, trouble swallowing or shortness of breath.[5]
Before You Start
A few things change how safe these medicines are for you. Mention each one in your questionnaire:
- any past pancreatitis, gallbladder disease or kidney disease[4]
- every medicine you take, especially for diabetes[7]
- whether you use hormonal birth control pills, if you are requesting tirzepatide
Tirzepatide may make hormonal birth control pills work less well. The NHS advises also using condoms for 4 weeks after you start and for 4 weeks after each dose increase.[5][6] One option is the FC2 female condom, an internal condom that a clinician can prescribe and we ship to your door.
Weight loss medicines should not be used during pregnancy or while trying to get pregnant.[3] We do not treat anyone who is pregnant.
Compounded GLP-1 medicines are prepared by a licensed pharmacy for each patient. Before you inject, make sure you know exactly how to measure your dose, because the FDA has had reports of side effects from dosing mistakes.[8] If anything is unclear, send us a message through your secure online account.
FAQ
How long does semaglutide nausea last?
For most people, nausea is worst in the first weeks and after each dose increase. Then it eases.[1][3] If it does not settle, send us a message through your secure online account.
Are tirzepatide side effects worse than semaglutide side effects?
Both mainly cause stomach and bowel side effects. One trial compared the two directly. These were the most common side effects in both groups, and most were mild to moderate.[9]
Who can get tirzepatide or semaglutide through Starfish.com?
These medicines are usually prescribed for adults with a BMI of 30 or more. A BMI of 27 or more can also qualify if you have a weight-related health problem, such as high blood pressure.[3] We treat adults aged 18 to 80 who are not pregnant. A licensed clinician reviews your questionnaire and prescribes only if it is appropriate.
Should I stop if I get side effects?
Mild side effects often ease with time, and the NHS advises carrying on unless you are told to stop.[3][7] Stop and get medical care right away for severe stomach pain that does not go away.[4][6]
Start Your GLP-1 Request
A licensed clinician reviews your answers and, if treatment is right for you, issues a prescription within 1 to 2 hours. Your medication is mailed to you.
References
- Jastreboff AM, et al. “Tirzepatide Once Weekly for the Treatment of Obesity.” New England Journal of Medicine, 2022. https://doi.org/10.1056/NEJMoa2206038
- Wilding JPH, et al. “Once-Weekly Semaglutide in Adults with Overweight or Obesity.” New England Journal of Medicine, 2021. https://doi.org/10.1056/NEJMoa2032183
- National Institute of Diabetes and Digestive and Kidney Diseases. “Prescription Medications to Treat Overweight & Obesity.” https://www.niddk.nih.gov/health-information/weight-management/prescription-medications-treat-overweight-obesity
- U.S. National Library of Medicine, MedlinePlus. “Semaglutide Injection.” https://medlineplus.gov/druginfo/meds/a618008.html
- U.S. National Library of Medicine, MedlinePlus. “Tirzepatide Injection.” https://medlineplus.gov/druginfo/meds/a622044.html
- NHS. “Tirzepatide: a medicine to manage type 2 diabetes and treat obesity.” https://www.nhs.uk/medicines/tirzepatide/
- NHS. “Semaglutide: a medicine to manage type 2 diabetes or treat obesity.” https://www.nhs.uk/medicines/semaglutide/
- U.S. Food and Drug Administration. “FDA’s Concerns with Unapproved GLP-1 Drugs Used for Weight Loss.” https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss
- Aronne LJ, et al. “Tirzepatide as Compared with Semaglutide for the Treatment of Obesity.” New England Journal of Medicine, 2025. https://doi.org/10.1056/NEJMoa2416394
- Wharton S, Davies M, Dicker D, et al. “Managing the gastrointestinal side effects of GLP-1 receptor agonists in obesity: recommendations for clinical practice.” Postgraduate Medicine, 2022. https://doi.org/10.1080/00325481.2021.2002616
