Retatrutide side effects

The information below has been taken only from phase 2 and phase 3 trials published in peer-reviewed journals and from regulatory agency statements. All of these trials were funded by the manufacturer. ^{[3] [4] [5]} Dose groups are referred to only as “low, medium, high.”

What are the most common side effects of retatrutide?

Gastrointestinal complaints come first in every trial:

• Phase 2, obesity (338 adults, 48 weeks): Gastrointestinal events were dose-dependent, mostly mild to moderate in severity, and decreased in part with a lower starting dose. ^[1]
• Phase 2, type 2 diabetes (281 people): Mild to moderate gastrointestinal events, including nausea, diarrhea, vomiting and constipation, occurred in 35% in the retatrutide groups, 13% on placebo and 35% on the comparator GLP-1 drug dulaglutide; in the retatrutide groups they ranged from 13% in the lowest dose group to 50% in one dose arm. ^[2]
• TRIUMPH-1 (2,339 adults with obesity, 80 weeks): According to the published abstract, the most common adverse events were gastrointestinal. ^[3]
• TRIUMPH-2 (1,152 adults with obesity and type 2 diabetes, 80 weeks): ^[4]

• TRANSCEND-T2D-1 (537 people with type 2 diabetes, 40 weeks): The most common adverse events were generally mild to moderate gastrointestinal events and decreased over time. Discontinuation of treatment due to adverse events was 2–5% in the retatrutide groups and 0% on placebo. ^[5]

What is dysesthesia, and how often was it seen with retatrutide?

Dysesthesia is abnormal perception of touch or skin sensation (such as tingling, burning, tenderness). In TRIUMPH-2 it was reported in 4–7% in the retatrutide groups and 1% in the placebo group; frequency rose with dose. ^[4] The cause of this finding, how long it lasted, and whether it resolved after the drug was stopped have not yet been explained.

Does retatrutide affect heart rate and blood pressure?

• Heart rate: In the phase 2 obesity trial, resting heart rate rose in a dose-dependent manner; the increase peaked at week 24 and then decreased. ^[1]
• Blood pressure: In TRIUMPH-2, hypotension was seen in 5–6% in the medium and high dose groups and below 1% on placebo. ^[4]

Does retatrutide lower blood sugar too much?

Severe hypoglycemia was not reported in two trials in people with type 2 diabetes: in the phase 2 trial the participants were being treated with diet-exercise or metformin, and in TRANSCEND-T2D-1 with diet and exercise alone. ^{[2] [5]} The participants in these two trials were not using insulin or sulfonylureas; the results cannot be carried over to people using these drugs.

Were there deaths in the trials?

In TRIUMPH-2, 2 participants in the low dose group, 3 in the medium dose group, 1 in the high dose group and 1 in the placebo group died; the investigators judged all of the deaths unrelated to the study drug. ^[4] In TRANSCEND-T2D-1, two deaths occurred in the low dose group and were found unrelated to the drug. ^[5] No deaths were reported in the phase 2 diabetes trial. ^[2] The assessment of relationship belongs to the investigator, and small numbers do not allow an independent conclusion.

Does retatrutide cause muscle loss?

There is only a small substudy for this question. In the DXA body composition substudy of the phase 2 diabetes trial, total fat mass at 36 weeks fell by 23.2% in the highest dose group and 4.5% on placebo. The authors find the ratio of lean mass loss to total weight loss similar to other obesity treatments; however, only 103 of the 189 people in the substudy completed treatment and both measurements, and all of the authors are employees of the manufacturer. Serious adverse events ranged from 0% to 9% between groups and no deaths were reported. ^[10] Effects on muscle strength, bone and physical function cannot be evaluated with these data.

What happens when retatrutide is stopped?

This question has not been studied enough. In the phase 2 liver substudy, some weight regain was observed at the safety visit 4 weeks after treatment ended. ^[6] The course after longer discontinuation is not known from these data. Weight regain after discontinuation with licensed GLP-1 drugs is covered in separate guides: Tirzepatide, GLP-1 agonists.

What is still unknown?

• Long-term safety: The longest published phase 3 trials are 80 weeks. ^{[3] [4]}
• Cardiovascular events: The endpoints of the phase 3 trials are weight, HbA1c, joint pain and the sleep apnea index; they were not designed to measure heart attack, stroke or death. ^[3] The cardio-renal outcomes trial that will measure these events (TRIUMPH-Outcomes) was ongoing according to the 2025 design publication. ^[11]
• Groups not studied: The published phase 3 trials enrolled adults aged 18 and over; safety is not known in children and adolescents, in pregnancy and in breastfeeding. ^{[4] [5]} Retatrutide has no established role in type 1 diabetes. ^[9]
• Independent data: All the large trials are manufacturer-funded and there are company employees among the authors. ^{[3] [4]}
• Regulatory evaluation: According to the FDA, retatrutide has not been found safe and effective for any condition; product information and warnings have not yet been formed in the licensing process. ^[7]

What extra risks do unlicensed products carry?

The safety findings in the clinical trials belong to the study drug of known purity, known amount and given by protocol. None of these conditions is assured in products sold online:

• Amount of content: In the analysis of three products sold as retatrutide in Australia and stating the same amount on the label, the measured content was 51.3%, 165% and 190% of the label; sterility and endotoxin were not tested. The authors note that only three samples were examined. ^[8]
• Regulatory review: The FDA states that unapproved GLP-1 products have not gone through safety, effectiveness and quality review before being sold, that retatrutide cannot be used in compounded drugs, and that it has warned companies marketing retatrutide to consumers. ^[7]
• Case report: A man in his mid-thirties with long-standing type 1 diabetes presented with severe vomiting, diarrhea, high blood sugar, ketonemia and acute kidney injury shortly after injecting himself with a product bought online and sold as retatrutide in order to lose weight; ketoacidosis did not develop, but the blood ketone level reached 4.3 mmol/L and intravenous insulin and fluids were needed. His partner, who used the same product, also had gastrointestinal complaints. Because Shigella grew in the stool culture, the author notes that causality cannot be established. ^[9]

This page does not recommend the use of retatrutide; it contains no dose, administration or sourcing information. For someone who has used retatrutide outside a clinical trial, evaluating a complaint that has occurred, together with reporting the product used, is a physician’s job.