Retatrutide
Not FDA-approved
Also known as: LY3437943
Retatrutide is an experimental lab-made peptide of 39 amino acids, given as a weekly injection. It activates three hormone receptors at once: GLP-1, GIP and glucagon. In large trials it lowered body weight and blood sugar, but it is still being studied and is not approved.
How it works
- It is a single peptide that switches on three hormone receptors. Two are for gut hormones, GLP-1 and GIP; the third is for glucagon, a hormone from the pancreas.
- In lab tests, it acts more strongly on the GIP receptor than on the GLP-1 and glucagon receptors, which it activates about equally.
- In obese mice, its GLP-1 and GIP actions cut food intake, and its glucagon action added weight loss by raising energy use.
- Glucagon on its own raises blood sugar. Even so, blood sugar fell on retatrutide in trials of people with type 2 diabetes.
- A fatty-acid chain attached to one of its amino acids makes it last long enough for once-weekly injections.
Evidence
Weight loss in obesity
An 80-week trial enrolled 2,339 adults with obesity and no diabetes. On the highest dose, body weight fell by 25% on average, versus about 4% on placebo. Among those in the trial with knee arthritis, knee pain eased more than on placebo.
Type 2 diabetes
A 40-week trial enrolled 537 adults whose type 2 diabetes was not well controlled by diet and exercise alone. On the highest dose, HbA1c, a three-month average of blood sugar, fell by about 1.9 percentage points, versus about 0.8 on placebo. In an 80-week trial of 1,152 adults with obesity and type 2 diabetes, weight fell by about 19% on the highest dose. It fell by about 5% on placebo.
Obstructive sleep apnea
Two placebo-controlled studies, nested in larger trials, enrolled adults with moderate-to-severe sleep apnea and overweight or obesity: 243 without diabetes, 448 with type 2 diabetes. At the start, they averaged about 56 to 59 breathing interruptions an hour of sleep. After 80 weeks, these fell by about 25 to 34 an hour on the two higher doses, versus about 10 on placebo.
Caveats
- Nausea, diarrhea, vomiting and constipation are the most common side effects. They rose with dose, were mostly mild to moderate, and were less common when treatment started at a lower dose.
- Heart rate rose with dose, peaked at around 24 weeks and then eased.
- In one large trial, 7% of people on the highest dose reported unusual skin sensations, such as tingling or burning (dysesthesia), versus 1% on placebo. Low blood pressure was also more common than on placebo.
- In the same trial, 8% to 12% on the two higher doses stopped treatment because of adverse events or death, versus 5% on placebo.
- Its long-term heart safety is not yet known. A large trial of heart outcomes is not due to finish until 2029.
- Trials excluded people with a personal or family history of medullary thyroid cancer or MEN 2, and people who had had pancreatitis.
- There are not enough safety data in pregnancy or breastfeeding.
References
- Jastreboff AM, et al. N Engl J Med. 2026 (published online September 29, 2026) (TRIUMPH-1).
- Bellido V, et al. Lancet. 2026;408:1455-1472 (TRIUMPH-2).
- Bajaj HS, et al. Lancet. 2026;407:2402-2413 (TRANSCEND-T2D-1).
- Grunstein RR, et al. N Engl J Med. 2026 (published online October 21, 2026) (TRIUMPH-1 and TRIUMPH-2 sleep apnea studies).
- Coskun T, et al. Cell Metab. 2022;34:1234-1247.
This page is for education only. It is not medical advice. Decisions about any treatment belong with a physician who knows your history.