Dose A1C reduction Average weight lost % body weight lost Retatrutide 12 mg injection 2.2% 47.4 lbs 20.9% Retatrutide 9 mg injection 2.2% 44.3 lbs 19.5% Ozempic 2 mg injection 1.8% 20.9 lbs 9.4% Dose Average weight lost % body weight lost Retatrutide 12 mg 55.8 lbs 22.6% Retatrutide 9 mg 52.7 lbs 21.6% Placebo 7.7 lbs 3.2% The trial enrolled 1,949 participants with an average starting weight of 245.6 lbs (111.4 kg).

Retatrutide is a novel triple agonist targeting the receptors of glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), and glucagon. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. It is only available to participants in clinical trials and cannot be legally purchased, prescribed, or compounded. Multiple black market sellers of the peptide emerged before approval of the Lilly drug, leading to multiple lawsuits with Lilly as the plaintiff. Safety assessments also indicate a low risk of hypoglycemia and no significant elevation in cardiovascular or hepatic adverse events in non-diabetic populations across published studies. Adverse events are most commonly gastrointestinal symptoms such as nausea and diarrhea, with relatively low rates of study discontinuation and infrequent serious adverse events reported during trials.

The results were published in The Lancet in September 2026. Their average starting weight was 234.6 lbs (106.4 kg), their average BMI was 38.2, and their average A1C was 7.7%. Dose Average weight lost % body weight lost Retatrutide 12 mg 70.3 lbs 28.3% Retatrutide 9 mg 64.4 lbs 25.9% Retatrutide 4 mg 47.2 lbs 19.0% Placebo 5.5 lbs 2.2% Results that include everyone who was enrolled, including people who stopped treatment, are usually a little lower. Retatrutide works by activating the receptors these hormones normally act on.

Compared to placebo, retatrutide showed a statistically significant achievement of ≥5%, ≥10%, and ≥15% weight loss targets after 24 weeks of treatment. However, there were some concerns regarding the randomization process in the study of Urva et al, leading to an overall risk of bias categorized as “some concerns.” Based on the Cochrane Risk of Bias 2 tool, two studies had a low overall risk of bias (Figure 2). Three RCTs were included in our analysis; two of them included only diabetic obese patients,24,26 and the third study was conducted on nondiabetic obese patients.25 The total number of patients was 878, with 748 receiving retatrutide and 130 receiving placebo. We used RevMan (version 5.4) to analyze data extracted from the included studies.23 Continuous outcomes were combined as mean differences (MD) with corresponding 95% confidence intervals (CI). Glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) are incretin hormones that have a role in nutrient metabolism.

Several ongoing clinical trials (the TRIUMPH and TRANSCEND-T2D trials) are assessing the effect of retatrutide on weight loss and glycemic control in relation to varying outcomes. Further long-term studies are warranted to confirm these findings and to fully elucidate the clinical benefits of retatrutide. Our meta-analysis supports the efficacy and safety of retatrutide as a promising therapeutic option for obesity management.

It is a triple hormone receptor agonist on the GLP-1, GIP, and glucagon receptors. In trials, the dose started at 2 mg and was increased every four weeks. It is more accurately described as a triple agonist, sometimes informally called a "triple G" drug, than as a standard GLP-1 medicine. The FDA would then review the application, which can take up to about a year depending on the type of review. It is still in development and is not an FDA-approved medicine, so no commercial cost has been set.

However, challenges such as high initial costs and limited acceptance decrease the generalization of bariatric surgery as a strategy to lower the obesity impact on public health.2 Retatrutide demonstrated significant improvements in body weight and metabolic outcomes among adults with obesity and had an appropriate safety profile. RevMan software (version 5.4) was used for analysis, with subgroup evaluation by dose (4 mg, 8 mg, 12 mg). PubMed, Scopus, Web of Science, and Cochrane databases were searched from inception until May 2024.

The remaining seven trials, including TRIUMPH-1 and TRIUMPH-2 (the core obesity trials), are expected to read out by mid-to-late 2026. Eli Lilly’s registrational trial programme for retatrutide is called TRIUMPH. The substantial weight loss achieved in clinical trials, coupled with meaningful improvements in metabolic health markers, positions retatrutide as a potentially transformative option for patients struggling with obesity and its complications. Long-term efficacy and safety data beyond the current trial durations will be essential for understanding the medication’s role in chronic obesity management.

Investigating the mechanisms underlying individual variability in response to retatrutide could provide insights for personalized obesity treatments. Future studies should focus on the long-term outcomes of retatrutide treatment, including its impact on obesity-related complications and quality of life. Long-term data on the sustainability of weight loss and the safety of retatrutide are also lacking, emphasizing the need for further research. These results underscore retatrutide’s potential as a promising therapeutic agent for managing hyperglycemia and obesity in individuals with T2DM.24

Urinary tract infections were also slightly more common with retatrutide in TRIUMPH-2. In TRIUMPH-1, it occurred in 5.1%, 12.3% and 12.5% of people taking 4 mg, 9 mg and 12 mg, compared with 0.9% on placebo. The most common side effects of retatrutide in clinical trials were digestive, including nausea, diarrhea, vomiting and constipation. Full results have not yet been presented at a medical meeting or published in a peer-reviewed journal. The trial enrolled 1,298 adults with type 2 diabetes whose blood sugar was not well controlled with metformin, with or without an SGLT2 inhibitor. It compared once-weekly retatrutide (9 mg or 12 mg) with once-weekly Ozempic 2 mg injection, the highest approved dose of Ozempic for type 2 diabetes.

The trial also reported reductions in knee-osteoarthritis pain and the severity of obstructive sleep apnea. In September 2026, results from two phase III trials were published. Phase III trials are being conducted as part of the TRIUMPH clinical development program. Retatrutide was initially studied in a phase II trial involving adults without diabetes who had obesity or overweight. Furthermore, agonism of the glucagon receptor increases energy expenditure and promotes fat loss and metabolic activity. These effects have not been linked to retatrutide in current trials.

Because it is not FDA approved, there is no legal way to obtain it for personal use outside a trial. Zepbound and Mounjaro are once-weekly injections, and retatrutide is being studied as a once-weekly injection. Wegovy and Ozempic are available as a once-weekly injection or a once-daily tablet. It cannot be prescribed, purchased or compounded outside of a trial. Full, formally reviewed safety information will only be available if the FDA approves the medicine.

This highlights retatrutide’s potential to be a highly recommended therapeutic option for achieving clinically meaningful weight loss in individuals with obesity. The absence of significant heterogeneity in most subgroup analyses further strengthens the reliability of these findings. The findings of our meta-analysis provide robust evidence for the efficacy and safety of the triple-hormone-receptor agonist retatrutide in obesity treatment. Compared to placebo, patients receiving retatrutide experienced higher occurrences of nausea, vomiting, decreased appetite, diarrhea, and constipation (Table 4). CI indicates confidence interval; FPG, fasting plasma glucose; HbA1c, hemoglobin A1c; I2, statistical heterogeneity (%); MD, mean difference; OR, odds ratio.

The trial’s findings suggest that retatrutide strikes a favorable balance between safety, glucose-lowering efficacy, and weight reduction. The results of the Jastreboff et al trial demonstrated that participants receiving the 12 mg dose of retatrutide experienced a mean weight reduction of 24.2% after 48 weeks. http://www.mkmbiolabs.com/ of glucagon and GIP receptor agonism to lower lipid levels in the blood and boost fatty acid oxidation could also help in reducing ectopic fat and enhancing cell health in various tissues.8,31 Further clinical trials will be required to determine the impact of retatrutide treatment on long-term clinical outcomes.

It is only available to participants in clinical trials and cannot be legally purchased, prescribed or compounded. Semaglutide (Ozempic, Wegovy) acts on one receptor (GLP-1), and tirzepatide (Mounjaro, Zepbound) acts on two receptors (GIP and GLP-1). Because it acts on all three receptors, it has been called a "triple agonist", "triple G" weight-loss medicine, or GLP3. Retatrutide is an investigational triple receptor agonist being studied for weight loss, type 2 diabetes, and other weight-related conditions.

Another trial demonstrated that retatrutide improved glycemic control more than dulaglutide, with A1C reductions as great as 2.16% with retatrutide versus 1.36% with dulaglutide at 36 weeks (5). Like other incretin mimetics, it is structurally similar to GIP, with alterations in the peptide backbone to increase agonist activity at the GIP, GLP-1, and GCG receptors (6). Phase 1 and 2 trials published to date have demonstrated its superior effects for both weight loss and glycemic control (4–6).