GLP-1 side effects ranked by trial frequency

The short answer: across the approved GLP-1 drugs, stomach and gut effects dominate the list, led by nausea, diarrhea, vomiting, and constipation. They are common, mostly mild to moderate, and cluster during dose increases. The rarer label warnings, such as pancreatitis and gallbladder disease, happen far less often but are the ones to know by name.

This list ranks side effects by how often they occurred in the trials summarized on the FDA labels, with placebo rates beside them. It anchors to our evidence grades: semaglutide and tirzepatide are both graded human RCT, so their numbers come from large randomized trials. It is not medical advice and does not cover dosing.

How we ranked

We used the adverse reaction tables on the current FDA labels. For semaglutide, that is the Wegovy 2.4 mg injection in adults with obesity or overweight. [1] For tirzepatide, it is the pooled weight-reduction trials behind Zepbound, shown here at the 15 mg dose unless noted. [2] Placebo rates matter: some nausea and headache happens to people on no drug at all.

The common side effects, ranked

1. Nausea. Wegovy 44% versus 16% on placebo. [1] Zepbound 25% to 29% across doses versus 8%. [2]

2. Diarrhea. Wegovy 30% versus 16%. [1] Zepbound 23% versus 8%. [2]

3. Vomiting. Wegovy 24% versus 6%. [1] Zepbound 13% versus 2%. [2]

4. Constipation. Wegovy 24% versus 11%. [1] Zepbound 11% at 15 mg and 17% at 5 mg, versus 5%. [2]

5. Abdominal pain. Wegovy 20% versus 10%. [1] Zepbound 10% versus 5%. [2]

6. Headache. Wegovy 14% versus 10%. The gap over placebo is small. [1]

7. Fatigue. Wegovy 11% versus 5%. [1] Zepbound 7% versus 3%. [2]

8. Indigestion (dyspepsia). Wegovy 9% versus 3%. [1] Zepbound 10% versus 4%. [2]

9. Dizziness. Wegovy 8% versus 4%. [1] Zepbound 4% versus 2%. [2]

10. Injection site reactions, hair loss, and belching. On the Zepbound label, injection site reactions were reported by 8% versus 2%, hair loss by 5% versus 1%, and belching by 5% versus 1%. [2]

The trial papers tell the same story. In STEP 1, nausea and diarrhea were the most common adverse events with semaglutide, typically transient and mild to moderate. [3] In SURMOUNT-1, gastrointestinal events were the most common with tirzepatide and were mostly mild to moderate, occurring mainly during dose escalation. [4] In SURMOUNT-5, the head-to-head trial, both groups showed the same pattern. [5]

How many people stop

Discontinuation is a useful single measure of tolerability. On the Wegovy label, 6.8% of adults stopped the injection for adverse reactions versus 3.2% on placebo. [1] On the Zepbound label, 4.8%, 6.3%, and 6.7% stopped on the 5, 10, and 15 mg doses versus 3.4% on placebo, and gastrointestinal reactions alone accounted for 1.9% to 4.3% versus 0.5%. [2]

The less common warnings that matter more

These are rarer, but they appear in the warnings sections of the labels, and they are the reasons to call a prescriber rather than wait it out.

• Gallbladder disease. Gallstones in 1.6% on Wegovy versus 0.7% on placebo, and gallbladder inflammation in 0.6% versus 0.2%. [1]
• Acute pancreatitis. 0.2 cases per 100 patient-years on Wegovy versus fewer than 0.1 on placebo. [1]
• Kidney injury from dehydration. 0.4 versus 0.2 cases per 100 patient-years on Wegovy; the label ties this risk to fluid loss. [1]
• Low blood sugar in type 2 diabetes. 6.2% on Wegovy versus 2.5% on placebo in patients with diabetes. The risk rises with insulin or sulfonylureas. [1]
• Faster heart rate. Mean increases of 1 to 4 beats per minute on Wegovy. [1]
• Aspiration during anesthesia. Both labels warn about pulmonary aspiration during general anesthesia or deep sedation, so tell every clinician before a procedure. [1] [2]
• Thyroid C-cell tumors. A boxed warning on both labels, based on rodent studies. Human relevance is unknown, and the drugs are contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2. [1] [2]

Unapproved and compounded products

For how compounded and research-only products differ from approved drugs on safety, see are peptide injections safe?

Retatrutide is not approved. In topline phase 3 results from TRIUMPH-1, released by the manufacturer and not yet peer reviewed, the common adverse events at 12 mg were nausea (42.4% versus 14.8% on placebo), diarrhea (32.0% versus 13.5%), constipation (26.1% versus 10.9%), and vomiting (25.3% versus 4.8%). Dysesthesia, an abnormal skin sensation, occurred in 12.5% versus 0.9%, and 11.3% stopped for adverse events versus 4.9%. [6]

For compounded semaglutide and tirzepatide, FDA had received 990 and more than 730 adverse event reports respectively as of May 31, 2026, including reports of doses beyond those on the approved labels. [7]

The takeaway

Rank alone does not decide which drug fits. Our semaglutide vs tirzepatide comparison sets side effects next to efficacy and cost, the obesity condition page grades every option, and the GLP-1 hub covers the full class.