A groundbreaking weekly injection, designed to target three hormones, is making waves as a formidable competitor to well-known medications like Ozempic and Mounjaro. This new drug promises to be a significant breakthrough for individuals dealing with type 2 diabetes and obesity.
In a phase III clinical trial, the drug known as retatrutide demonstrated remarkable results. Participants with type 2 diabetes experienced an average weight loss of 15 percent, equating to about 33 pounds, while also achieving near-normal blood sugar levels.
Impressively, nearly 90 percent of those involved in the trial managed to effectively control their blood sugar levels. Additionally, almost 75 percent of participants with prediabetes saw their condition completely reversed.
Though the 15.3 percent weight reduction in diabetic patients is noteworthy, retatrutide’s true potential shines even brighter. For individuals dealing solely with obesity, the weight loss could reach up to a quarter of their total body weight.
In a phase 2 trial focused on obesity, participants without diabetes shed an average of 24.2 percent of their body weight, roughly 52 pounds, on a 12 mg dose. This is a substantial increase compared to the 15.3 percent, or 33 pounds, weight loss observed in the diabetes-focused trial.
People with type 2 diabetes consistently lose less weight on GLP-1-based drugs than those without diabetes, likely due to underlying metabolic differences such as insulin resistance and altered hormone signaling.
Retatrutide belongs to a class of drugs that mimic natural hormones involved in metabolism, but unlike popular medications such as Ozempic, which targets one hormone — GLP-1 — or Mounjaro, which targets two — GIP and GLP-1 — retatrutide is the first to target three: GIP, GLP-1 and glucagon.
The addition of glucagon is what makes the drug unique. While GLP-1 and GIP primarily suppress appetite and slow digestion, glucagon may also increase energy expenditure and promote fat burning, potentially leading to greater weight loss than current options.
Many patients with obesity or overweight-related conditions turn to GLP-1 medications as part of their treatment plan. An estimated 31 million Americans takes one of these drugs to lose weight (stock)
Ozempic, on average, causes a five to 15 percent weight loss and Mounjaro leads to weight loss in the range of 15 to 22 percent.
An estimated 31 million Americans have taken a weight-loss drug.
Retatrutide is not yet approved by the FDA or other regulatory agencies. It is being developed by Eli Lilly, which also makes tirzepatide and orforglipron, two other weight-loss medications sold as Zepbound and Foundayo, respectively.
But according to Marlee Bruno, a board-certified physician associate and founder of Pensacola, Florida medical spa Mind Body & Soul Medical, ‘patients are absolutely already asking about it.’
‘People read headlines, hear about new medications on social media and immediately want to know if it’s better than what they’re currently taking,’ she told the Daily Mail.
The drug is still being studied in a large phase 3 program called TRIUMPH, which is evaluating its safety and effectiveness in thousands of patients with obesity, type 2 diabetes and related conditions.
Bruno added: ‘What makes retatrutide interesting is that it targets three hormone pathways instead of one or two.
‘In theory, that could translate to even greater weight loss and metabolic improvements. But we still need more data before we know exactly where it fits in clinical practice.’
The latest TRANSCEND-T2D-1 trial results, published in The Lancet this week, enrolled 537 adults with early type 2 diabetes. Participants had been diagnosed with diabetes for about two and a half years on average and were not taking any other diabetes medications.
They were randomly assigned to receive either a placebo or one of three doses of retatrutide — 4 mg, 9 mg or 12 mg — once weekly for 40 weeks.
In the latest study on retatrutide in people with diabetes, the graph shows the percentage change in body weight from baseline to week 40 (assuming perfect adherence). People taking retatrutide lost weight steadily, with the 12 mg dose group achieving an average loss of 16.9 percent
The final Phase 3 trials (part of the TRIUMPH program) are expected to be completed throughout 2026, after which Eli Lilly can submit a New Drug Application. The FDA typically takes six to ten months to review an application after it is submitted and soonest approval will likely be in 2027
Researchers found that HbA1c, a key measure of blood sugar control over time, dropped by nearly two percentage points in the highest-dose group, compared to less than one point with the placebo.
Nearly 90 percent of participants on the 12 mg dose reached the target HbA1c of less than seven percent, and 40 percent achieved a completely normal HbA1c below 5.7 percent, all without any cases of dangerously low blood sugar.
The weight loss results were equally impressive. At 40 weeks, participants on the highest dose had lost an average of 15.3 percent of their body weight. For a person weighing 215 pounds, that amounts to about 33 pounds.
Those on the 9 mg dose lost 13.9 percent of their body weight, and those on the 4 mg dose lost 11.5 percent. By comparison, the placebo group lost just 2.6 percent.
A slightly higher figure of 16.9 percent comes from an ‘efficacy estimand,’ which assumes every participant took the drug perfectly for 40 weeks.
The 15.3 percent figure reflects real-world conditions, accounting for missed doses and dropouts.
Even more noteworthy, weight loss had not yet plateaued by the end of the 40-week study, suggesting that longer treatment could lead to even greater results.
The study also examined a combined outcome that researchers say better captures the drug’s overall benefit: achieving both excellent blood sugar control and clinically meaningful weight loss.
Up to 64 percent of participants on retatrutide achieved this composite goal, compared to just three percent of people on the placebo.
An earlier phase 2 obesity trial published in the New England Journal of Medicine suggested that women may lose more weight than men on retatrutide, and people with higher starting BMIs may also see greater results. But researchers stress that more studies are needed to understand who will benefit most.
Beyond blood sugar and weight, retatrutide also improved several other markers of cardiometabolic health, including blood pressure, cholesterol and prediabetes.
Systolic blood pressure dropped by about 5mmHg in retatrutide groups, compared to 1.5mmHg with placebo.
Cholesterol fell by up to 17 percent, while triglycerides, the fats in the blood, dropped by up to 34 percent.
Among participants who had prediabetes at the start, 72 percent of them returned to normal blood sugar levels after 40 weeks of retatrutide treatment.
As with other drugs in this class, gastrointestinal side effects were the most common.
Nausea, diarrhea, vomiting and constipation affected a significant number of participants, particularly during the first few weeks of treatment as doses were gradually increased.
A phase 2 obesity trial with retatrutide found that people without diabetes lost 24.2 percent of their body weight (about 52 pounds) on the 12 mg dose over 48 weeks, compared to just 2.1 percent on placebo. Weight loss had not plateaued by the end of the study, suggesting even greater results with longer treatment
However, most side effects were mild to moderate, and they tended to subside over time.
Discontinuation rates due to adverse events were low across retatrutide groups at around two to five percent.
No severe hypoglycemia was reported, a key safety finding for a diabetes drug. There were no cases of severe pancreas inflammation or thyroid cancer, though the study was not long enough to fully assess these rare risks.
Some participants experienced mild skin sensitivity or a temporary increase in heart rate. The increase in heart rate peaked around 24 weeks and then declined, a pattern similar to that seen with other GLP-1 drugs.
The results suggest retatrutide may outperform some current medications for obesity.
In a previous trial of semaglutide (Wegovy), patients lost about 14.9 percent of their body weight on the highest dose. With tirzepatide (Zepbound), weight loss reached about 20.9 percent.
Retatrutide is also being studied for other conditions, including knee osteoarthritis and obstructive sleep apnea, which could broaden its potential use by the tens of millions.
If ongoing phase 3 trials confirm these results and regulatory approval follows, retatrutide could become available by late 2026 or 2027.
However, a lack of FDA approval has not appeared to stop the drug from being prescribed or sold online.
On one website, it appears consumers can purchase a 5 mg vial of ‘research-grade’ retatrutide for $675.
And Reddit is rife with posts from people exchanging tips on which sites to buy the drug, how to mix it into a liquid solution at home and how to inject it.
In one thread, a user explained that the drug arrives as a powder that must be combined with bacteriostatic water — ‘Don’t use distilled though!’ — while another offered a referral code for a site that sells ‘research-grade’ retatrutide alongside syringes from Amazon.
Dozens of clinics across the country are openly advertising retatrutide, according to a CBS News investigation.
The practice breaks a long-standing medical rule — waiting for FDA approval before prescribing — and is fueling a commercial market for a drug that federal law prohibits from being sold.
Some physicians work with licensed compounding pharmacies that produce their own versions of retatrutide, sourcing the active ingredient from bulk suppliers.
As with other drugs in this class, gastrointestinal side effects were the most common. Nausea, diarrhea, vomiting and constipation affected a significant number of participants, particularly during the first few weeks of treatment as doses were gradually increased
While compounding pharmacies are legally permitted to make versions of FDA-approved drugs under certain conditions, the FDA says there is no legal justification for compounding an experimental drug that has never been approved.
Asked if there were any grounds to compound retatrutide, Scott Brunner, the CEO of the Alliance for Pharmacy Compounding, told CBS News: ‘Zero, none; none whatsoever.’
Nevertheless, at least five compounding pharmacies across Texas and Florida are openly making retatrutide and since 2024, the FDA has issued 14 warning letters to companies advertising retatrutide.
Other doctors are prescribing retatrutide labeled as ‘research grade’ or ‘for research use only,’ a disclaimer designed to shield sellers from legal liability.
These products come from unregulated suppliers that are not subject to FDA oversight for safety or purity. Doctors who use these sources argue that third-party lab certificates confirm the product’s content.
