Skip to content Retatrutide is a triple-receptor agonist acting on GLP-1 (glucagon-like peptide-1), GIP (glucose-dependent insulinotropic polypeptide), and glucagon receptors.
It is designed for once-weekly injection.
Obesity / overweight, including weight loss in people without diabetes.
Type 2 diabetes: lowering blood sugar (HbA1c) and the metabolic effects.
Non-alcoholic fatty liver disease (NAFLD) / reducing liver fat. In obesity trials, a substudy showed normalization of liver fat in many participants.
From Phase 2 trials:
In people with obesity (without diabetes), highest doses (especially ~12 mg weekly) led to ~24% average body weight loss over 48 weeks.
Even at 24 weeks, there were substantial reductions (e.g. ~17.5% in some dosing groups) versus placebo.
In people with type 2 diabetes, retatrutide led to both significant HbA1c reductions (≈1.3-2.0% in higher dose groups over ~36 weeks) and meaningful weight loss (~16-17% for highest dose) compared to placebo or active comparator.
The side effect profile in trials has been similar to other hormone-agonist/incretin class meds: chiefly gastrointestinal issues (nausea, vomiting, diarrhea, constipation).
Some other effects (e.g. transient increases in heart rate) have been observed, particularly at higher doses, but many adverse effects seem to diminish over time.
As of now, not FDA approved. It’s still in clinical development (Phase 2, moving into Phase 3).
Trials underway are evaluating its longer-term safety, efficacy, and broader outcomes (e.g. cardiovascular risk, weight maintenance, quality of life).
Because it activates three hormone receptors instead of one (like many GLP-1 agonists) or two (like GLP-1 & GIP dual agonists), the hope is that retatrutide might deliver greater weight loss, better metabolic improvements, or work in people who don’t respond well to current treatments.
Early results do suggest weight loss surpassing many existing approved agents (in trial settings), though side effects and long-term safety still need more data.
A meta-analysis published in 2025 (covering randomized controlled trials up to May 2024) included ~878 patients and found significant improvements in weight and metabolic markers using retatrutide in obese people.
Average weight loss ~ −14.33% vs baseline.
Reductions in body mass index, waist circumference, fasting plasma glucose, hemoglobin A1c, and blood pressure.
No significant increase in total adverse events vs placebo in that meta-analysis; though gastrointestinal events were more frequent.
From a Phase 2 trial (Jastreboff, etc): in people without diabetes, higher doses (~12 mg weekly) led to ~24% average body weight loss over 48 weeks.
In people with type 2 diabetes, retatrutide yielded both decent HbA1c reductions and weight loss. For example, at the higher doses, around ~16-17% body weight loss in ~36 weeks.
There is also evidence of benefits on other metabolic outcomes (waist circumference, blood pressure).
Trials underway include ones specifically looking at obesity with cardiovascular disease risk, relief of chronic low back pain in obese people, etc.
Gastrointestinal side effects are the most common: nausea, vomiting, diarrhea, constipation. These are dose-dependent and more common with higher doses. They often occur during dose escalation / early treatment.
Discontinuation rates due to adverse events are not unusually high; in many trials the discontinuation rates are similar to other drugs in this class when using proper titration.
Liver and kidney functions so far: no consistent or dose-dependent signals of liver toxicity (hepatotoxicity) in Phase 2; renal impairment not observed as a primary signal, though dehydration related to GI loss is a theoretical concern.
Cardiovascular markers: some increase in heart rate has been noted, especially at higher doses, in some participants. This is being closely monitored, since weight loss drugs (especially those affecting metabolic hormones) often need dedicated cardiovascular outcomes trials.
Long-term safety beyond ~1 year remains unproven. There isn’t good data yet for multi-year effects, or for rare adverse events.
Another area being watched is rapid weight loss risks (like gallstones, changes in gallbladder), potential impacts on bone density, nutrition, or other organs. These are standard risks in weight loss medications and weight loss generally. Some of that is speculative until more data accrues.
