Key Points
- Eli Lilly has announced that its experimental obesity drug, Retatrutide, has shown encouraging results in late-stage clinical trials for weight reduction. At the same time, the scientists observed significant pain relief in patients with knee osteoarthritis. They successfully published and completed the first of several planned studies for this once-weekly therapy.
- The company is positioning Retatrutide as the next key drug in its portfolio of obesity drugs, following the already available therapy Zepbound and an oral preparation also in development. It is expected that this position is in the field of metabolic therapies.
- Retatrutide is also known as the “triple G” because of its mechanism of action: it simultaneously mimics three hormones involved in appetite and energy balance regulation – GLP-1, GIP, and glucagon. Unlike therapies that target one or two hormonal pathways, this approach combines all three, achieving a broader metabolic effect.
The company Eli Lilly has announced that, according to available data, their innovative obesity treatment has achieved the most significant weight reduction in the final phase of the clinical trial. This result is evident compared with the currently available therapeutic options.
In addition to significant weight loss, the therapy also showed a positive effect on pain reduction in patients diagnosed with osteoarthritis of the knee, successfully ending the first study for the injection therapy.
In patients receiving the highest dose, the average weight loss after 68 weeks was 23.7%. This result refers to the total number of participants, regardless of whether they completed or discontinued the therapy. By analyzing patients who remained on therapy until the end of the study, the average weight loss reached 28.7%.
The company stated that in some participants, the reduction in body mass was so pronounced that they chose to withdraw from the study before its completion. Dr. Caroline Apovian from Brigham and Women’s Hospital evaluated the study’s results as exceptional, noting that the therapy can be compared to the effects of bariatric surgery in terms of the degree of weight loss achieved.
Dr. Apovian emphasized that Eli Lilly positions Retatrutide as a therapy intended primarily for patients with severe obesity – those whose body mass index (BMI) is greater than 35 or 40. The doctor noted that, according to study data, 84% of the included patients belonged to that category, indicating the drug’s target population.
The publication of the results also had a direct effect on the financial market: the company’s shares rose by 3% during trading on the same day. The first results indicate that the mechanism of action of this therapeutic option differs from that of existing injectable drugs and, so far, show a stronger effect on body weight reduction.
The company sees this drug as the next key pillar in its portfolio, building on the already available therapy Zepbound and the oral preparation. However, it has not yet been specified when the drug could be available on the market.
Retatrutide is a significant part of the company’s plan to maintain its leadership position over Novo Nordisk in the dynamic segment of obesity and diabetes drugs. According to estimates from some analysts, this market could reach around 100 billion dollars by the 2030s, intensifying competition among the leading pharmaceutical companies.
Retatrutide, in addition to the primary goal (reduction of body mass), achieved the second main outcome of the study – relief of pain and other symptoms in osteoarthritis of the knee. This disease is a chronic degenerative condition characterized by gradual damage to joint cartilage, accompanied by pain, stiffness, and reduced mobility.
Data published by Eli Lilly showed that up to 62.6% pain reduction was achieved when all subjects were included in the analyses. These results are based on a validated clinical questionnaire, routinely used for symptom assessment. Additionally, more than one in eight patients receiving the therapy were completely pain-free at the end of the trial.
One challenge with modern weight-loss drugs is the potential loss of lean body mass, including muscle. However, according to Dr. Apovian, the results indicate that in adults with severe obesity, Retatrutide therapy can improve physical function, adding that the reduction in body weight does not necessarily accompany a significant decrease in functional ability.
The published data exceeded market expectations in an analytical assessment published before the official results. Evan Sigerman of the investment house BMO Capital Markets announced that he expects a 20% to 23% reduction in body mass, with at least a 50% reduction in knee pain. Realized results exceeded those projections.
Retatrutide could represent a crucial option for patients who need weight loss, especially those with complications such as knee osteoarthritis, said Kenneth Custer, President of the Cardiometabolic Health Division at Eli Lilly.
In an analytical report, JPMorgan’s Chris Schott rated Retatrutide’s tolerability data (side effect frequency and intensity) as less favorable than Zepbound therapy. However, he stressed that such a safety report is not surprising, given the drug’s strong effect on reducing body mass.
According to available data, approximately 18% of patients who received the highest dose discontinued therapy due to adverse reactions, compared with 4% in the placebo group. Eli Lilly reported a dropout rate that was significantly correlated with baseline body mass index (BMI), and that some subjects discontinued therapy due to the subjective impression that weight loss was too pronounced.
Among patients with a BMI of 35 or greater who received the highest dose, 12% discontinued treatment. According to Schott’s estimate, that rate is closer to the percentages reported in clinical studies for Zepbound and Novo Nordisk’s injectable therapy Wegovy.
In a separate analysis, Ecan Sigerman of BMO Capital Markets noted that discontinuation data suggest the speed and intensity of weight reduction, particularly in patients with lower baseline BMI, may have been overstated. Nevertheless, he assessed that the study’s overall results leave a very strong impression and exceed earlier market expectations.
In patients receiving the highest dose of Retatrutide, approximately 43% reported nausea, while diarrhea and vomiting were experienced by approximately 33% and 20.9% of subjects, respectively.
More than 20% of patients also reported dysesthesia (nerve-related discomfort). Eli Lilly describes these side effects as mild.
The TRIUMPH-4 study was not exclusively focused on weight loss. Other trials, specifically designed for this purpose, may have shown different or even more pronounced results. Eli Lilly plans to publish data from seven more Phase 3 clinical trials by the end of 2026.
Retatrutide, also known as a “triple G” drug, works by mimicking three appetite–regulating hormones – GLP-1, GIP, and glucagon – unlike existing therapeutic options that target one or two hormones. Such an approach enables stronger appetite control and a greater impact on satiety than competing drugs.
Tirzepatide, the active substance in Zepbound, mimics GLP-1 and GIP, while Semaglutide, the active substance in Novo Nordisk’s Wegovy, acts only on GLP-1.
In late-stage clinical trials, patients receiving higher doses of Tirzepatide lost an average of about 20.9% of body weight, including all participants. Eli Lilly’s main rival, Novo Nordisk, is rapidly trying to catch up with the competition.
In March, the company announced that it had entered into a deal valued at up to $2 billion for the rights to an early-stage experimental drug from pharmaceutical company United Laboratories International.
Novo Nordisk’s drug represents a potential competitor to Retatrutide because it uses a similar triple approach to appetite regulation and blood sugar control. However, its therapy is still in early development, meaning it will be several years before it becomes available.
