Short answer: retatrutide is an investigational once-weekly injection from Eli Lilly that acts on three hormone receptors: GIP, GLP-1 and glucagon. It is not FDA-approved. Lilly has said it plans to file with the FDA in the first quarter of 2027.[3] In the published trials, the most common side effects were gastrointestinal: dose-related, mostly mild to moderate, and easing over time.[1][2] If you're in a trial or an expanded access program, the same gut basics that help on semaglutide and tirzepatide apply.
Retatrutide is all over the headlines and all over social media. Here's what the actual trials say about your gut, and what to do about it.
What is retatrutide?
It's the next step in a family of medicines you already know. Semaglutide (Ozempic, Wegovy) acts on one receptor, GLP-1 (you'll also see it written "GLP One"). Tirzepatide (Mounjaro, Zepbound) acts on two, GIP and GLP-1. Retatrutide adds a third, glucagon, which is why researchers call it a triple agonist.[1]
It's still investigational. Outside of clinical trials, the only legitimate access is a pre-approval expanded access program that a physician applies for.[4]
What do the trials show about GI side effects?
Phase 2 obesity trial (NEJM, 2023)
338 adults, 48 weeks, several doses against placebo. The most common side effects were gastrointestinal. They were dose-related, mostly mild to moderate, and partly reduced by starting at a lower dose (2 mg instead of 4 mg).[1]
Phase 3 type 2 diabetes trial (TRANSCEND-T2D-1, Lancet, 2026)
537 adults, 40 weeks. The most frequent side effects were generally mild to moderate GI events that subsided over time. Between 2% and 5% of people on retatrutide stopped because of side effects, versus 0% on placebo. The authors called the side-effect profile consistent with other medicines that act on GLP-1.[2]
Phase 3 obesity trials (TRIUMPH)
Lilly has reported topline results, and coverage lists diarrhea, nausea, constipation and vomiting among the reported side effects.[3] Full peer-reviewed GI numbers weren't published when we wrote this. We'll update this page when they are.
Why would it upset your gut?
The GLP-1 part is the likely driver. GLP-1 medicines slow how fast the stomach empties. The Wegovy prescribing information says it directly for semaglutide.[5] Slower emptying means fullness, nausea and bloating up top, and slower, harder stools further down. The phase 3 authors saw the pattern you'd expect from any drug with GLP-1 activity.[2]
What helps
Nobody has run a gut-comfort trial in retatrutide users yet. The steps that help across the GLP-1 class come from a 2022 multidisciplinary expert consensus:[6]
- Eat smaller, slower, and stop at full.
- Go easier on fat. Greasy meals sit longest.
- Drink generously, especially with nausea, vomiting or diarrhea.
- Get enough fiber, added slowly, if constipation is the problem.
- Get some fresh air and light activity, and don't lie down right after eating.
We go deeper on each one in our guides to constipation, bloating and gas, and nausea and diarrhea on a GLP-1.
Don't buy it online
Retatrutide isn't approved, so anything sold online as retatrutide, including "research-use" products, is unregulated. A 2026 clinical review warns these products carry real risks: contamination, manufacturing impurities and inaccurate dosing.[7] The only legitimate routes are a clinical trial or a physician-run expanded access program.
Can a probiotic help?
Nobody has studied probiotics in people on retatrutide. Probiotics are supplements, not drugs. No probiotic replaces, copies or boosts retatrutide, semaglutide or tirzepatide, and none should change how you take them.*
See what your gut is doing on a GLP-1. Then get a formula built for it.
A Flore gut test maps your microbiome from a sample you take at home. We build a personalized formula from what we find, and every formula can carry up to two boosters. For people on GLP-1 medications, the boosters we reach for are Barrier Defense III (Bifidobacterium longum) and Digestion Aid I (Bacillus coagulans), to support digestive comfort.*
Not ready to test? Take the GoodOnes quiz to find a simple, single-job formula to start with.*
Start with your gut data → How the test worksBefore you add any supplement: if you take an oral semaglutide pill (Rybelsus or the Wegovy pill), don't take it within 30 minutes after your pill. If you have gastroparesis, a past bowel obstruction or bezoar, or trouble swallowing, talk to your clinician first.
When to call your clinician
- Severe stomach pain that won't go away, with or without vomiting
- You can't keep fluids down, or you're dizzy or barely peeing
- No bowel movement for several days, or you can't pass gas
- Diarrhea that lasts more than a couple of days, or any blood in your stool
If you're in a trial, report side effects to the study team. Don't change your dose on your own.
Frequently asked questions
Is retatrutide FDA-approved?
No. As of September 2026 retatrutide is still investigational. Eli Lilly has said it plans to file with the FDA in the first quarter of 2027. Outside of clinical trials, access runs through a physician-requested pre-approval expanded access program.
What are the most common side effects of retatrutide?
Gastrointestinal ones. In the phase 2 obesity trial they were the most common side effects, dose-related and mostly mild to moderate. In the phase 3 TRANSCEND-T2D-1 trial they were generally mild to moderate and subsided over time.
Is retatrutide a GLP One drug?
Partly. GLP One is another way people write GLP-1. Retatrutide acts on the GLP-1 receptor plus two others, GIP and glucagon, which is why it is called a triple agonist. Semaglutide acts on GLP-1 alone and tirzepatide on GIP and GLP-1.
Is it safe to buy retatrutide online?
No. Retatrutide isn't approved, so anything sold online as retatrutide, including so-called research-use products, is unregulated. Clinicians have warned about contamination, impurities and inaccurate dosing in these products. The only legitimate routes are a clinical trial or a physician-run expanded access program.
Do probiotics help retatrutide side effects?
Nobody has studied that. The everyday steps that help GI side effects on semaglutide and tirzepatide, like smaller meals, less fat, fluids and fiber added slowly, are the reasonable place to start. A probiotic never replaces your clinician's advice or your medication.
Keep reading
- Metabolic gut health hub: Akkermansia, GLP-1 and your gut
- GLP-1, probiotics and weight: what the science really says
- GLP-1 and your gut: the bigger picture
- Constipation on a GLP-1: why it happens and what helps
- Bloating and gas on a GLP-1
- Nausea and diarrhea on a GLP-1
- Psyllium husk: benefits, dose, and is it a prebiotic?
This article is educational and is not medical advice. It does not replace your prescriber. Never stop, skip or change a GLP-1 dose on your own.
*These statements have not been evaluated by the Food and Drug Administration. Flore products are not intended to diagnose, treat, cure, or prevent any disease.
Ozempic, Wegovy and Rybelsus are registered trademarks of Novo Nordisk A/S. Mounjaro and Zepbound are registered trademarks of Eli Lilly and Company. Flore is not affiliated with or endorsed by either company.
Retatrutide is an investigational medicine from Eli Lilly and Company and has no approved brand name.
Sources
- Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial. N Engl J Med. 2023;389(6):514-526. PubMed 37366315
- Bajaj HS, et al. Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1) [phase 3 trial]. Lancet. 2026;407(10546):2402-2413. PubMed 42250575
- Lilly, with new data, to seek FDA approval of obesity drug retatrutide. BioPharma Dive, July 23, 2026.
- Pre-approval Expanded Access of Retatrutide (LY3437943). ClinicalTrials.gov NCT07629401.
- WEGOVY (semaglutide) injection, Prescribing Information. U.S. Food and Drug Administration, 2024.
- Gorgojo-Martínez JJ, et al. Clinical recommendations to manage gastrointestinal adverse events in patients treated with GLP-1 receptor agonists: a multidisciplinary expert consensus. J Clin Med. 2022;12(1):145. PubMed 36614945
- Moiz A, O'Keefe EL, O'Keefe JH. Dangers of injectable peptides and other unregulated "biohacking" drugs. Mo Med. 2026;123(4):337-343. PubMed 42757290