GLP-1 Side Effects and Safety

These are effective medications with a real side effect profile. Most of it is gastrointestinal and manageable, some of it is not, and one widely repeated concern has now been formally withdrawn.

Common side effects

From the Zepbound prescribing information, reactions occurring in 5 percent or more of patients:

• Nausea, 25 to 29 percent
• Diarrhea, 19 to 23 percent
• Constipation, 11 to 17 percent
• Vomiting, 8 to 13 percent
• Abdominal pain, 9 to 10 percent
• Indigestion, 9 to 10 percent
• Injection site reactions, 6 to 8 percent
• Fatigue, 5 to 7 percent

Hair loss, belching and heartburn are also listed among reported effects. The pattern is similar across the class.

Most of this is worst during dose escalation and settles. It is also the main reason people stop. In the SURMOUNT-5 trial, 6.1 percent discontinued tirzepatide and 8.0 percent discontinued semaglutide because of adverse events.

The boxed warning

Both semaglutide and tirzepatide carry a boxed warning about thyroid C-cell tumors. The wording is specific and worth reading exactly: in rodents, these drugs cause thyroid C-cell tumors. It is not known whether they cause thyroid C-cell tumors, including medullary thyroid carcinoma, in humans.

They are contraindicated if you have a personal or family history of medullary thyroid carcinoma, or Multiple Endocrine Neoplasia syndrome type 2. They are also contraindicated in anyone with a known serious hypersensitivity to the drug or its ingredients.

The distinction between a rodent finding and a human risk matters. It is not a statement that these drugs cause thyroid cancer in people. It is a statement that the question is open, which is why the family history contraindication exists.

Orforglipron (Foundayo) carries the same boxed warning and the same contraindications, with one difference worth noting: its label states that orforglipron itself did not produce tumors in rodents. The warning is applied to the class.

What the FDA removed in January 2026

Reports of suicidal thoughts on GLP-1 medications generated substantial concern and a labelling warning. On 13 January 2026 the FDA requested removal of that warning from Saxenda, Wegovy and Zepbound labelling.

The review behind the decision was substantial: a meta-analysis of 91 clinical trials covering more than 107,000 patients, a retrospective study of 2.2 million healthcare claims, and published observational studies. The FDA concluded there is no increased risk of suicidal ideation or behaviour associated with these medications, with no elevated risk against placebo or other diabetes drugs.

If you read something claiming otherwise, check its date.

Serious risks to know about

These are less common but need prompt attention. Contact your prescriber if you experience:

• Severe, persistent abdominal pain, especially radiating to the back, which may indicate pancreatitis
• Right upper abdominal pain, fever, or yellowing of skin or eyes, which may indicate gallbladder disease. Rapid weight loss from any cause raises gallstone risk, surgery included.
• Persistent vomiting or inability to keep fluids down, which risks dehydration and kidney injury
• Vision changes, particularly if you have diabetic retinopathy
• Signs of a serious allergic reaction

This is not the complete list. The full prescribing information for your specific medication is the authoritative source, and your prescriber and pharmacist should go through it with you.

Muscle loss

Weight lost on these medications is not all fat. Preserving lean mass through adequate protein and resistance training is a live concern, and one that matters more for bariatric patients who may already be at risk. Raise it with your dietitian rather than leaving it to chance.

Pregnancy

These medications are not for use in pregnancy, and weight loss during pregnancy is not advised. If you could become pregnant, discuss contraception and planning with your prescriber before starting. This is particularly relevant after bariatric surgery, where fertility often improves.