In a Lilly-funded phase 2 trial, adults with obesity who received the highest dose of retatrutide lost an average of 24.2% of their body weight over 48 weeks. The results are promising, but larger and longer studies are needed to establish the drug’s safety and lasting effects.
TLDR: A Lilly-developed experimental drug that targets three hormone pathways produced an average 24.2% weight loss at its highest dose in a 48-week phase 2 trial. Gastrointestinal side effects were common, and longer, larger trials are needed to clarify safety and sustained benefits.
An experimental medicine from Eli Lilly led to substantial weight loss in a midstage clinical trial, adding a new candidate to the fast-moving field of obesity treatment. Participants receiving the highest tested dose of retatrutide lost an average of 24.2% of their body weight after 48 weeks, according to results published in 2023 in the New England Journal of Medicine.
The phase 2 trial enrolled 338 adults with obesity, or overweight with a related health condition. Participants did not have diabetes. Researchers randomly assigned them to receive weekly injections of retatrutide at different doses or a placebo. The study was conducted at multiple sites and funded by the drug’s maker, Lilly; company researchers were among the study authors. The weekly injections were escalated gradually in some groups, a strategy intended to improve gastrointestinal tolerability; trial reports also tracked changes in waist circumference and cardiometabolic measures, not weight alone.
Retatrutide is designed to activate receptors for three hormones: GIP, GLP-1 and glucagon. These signaling systems influence appetite, blood sugar, and energy use. Existing medicines such as semaglutide and tirzepatide act on one or two of these targets. The combination is intended to affect several pathways involved in metabolism, though the trial cannot determine precisely how much each target contributed to weight change.
At 48 weeks, average weight loss ranged from 8.7% among participants receiving the lowest retatrutide dose to 24.2% at the highest dose. The placebo group lost an average of 2.1%. A greater share of people in the higher-dose groups also reached weight-loss thresholds of 15%, 20% and 25%. Those are group averages, not a prediction of how much any particular person would lose.
The findings drew attention because the highest-dose result approached weight reductions reported for some surgical procedures and exceeded results from several earlier obesity-drug trials. However, comparisons across separate studies can be misleading: participants, trial duration, and methods may differ. Retatrutide has not been directly compared with other medicines in a head-to-head trial, and a phase 2 result does not establish long-term effectiveness or safety.
Side effects were common, particularly nausea, diarrhea, vomiting and constipation. They were generally described as mild or moderate, and occurred more often at higher doses. Some participants stopped treatment because of adverse events. Researchers also observed a dose-related increase in heart rate that peaked around 24 weeks and later declined. These findings make longer monitoring important, especially because obesity treatment may continue for years.
The trial’s design also limits what can be concluded. It lasted 48 weeks, involved a few hundred participants, and excluded people with diabetes. It therefore could not reliably identify uncommon harms or show whether weight loss would persist over several years. Participants received lifestyle counseling as well as injections, and the results do not establish that medication alone explains every change.
Obesity is a chronic condition associated with increased risk of type 2 diabetes, heart disease and other health problems. Even so, body weight is only one measure of health. Future studies will need to assess whether retatrutide improves outcomes such as blood pressure, blood sugar and cardiovascular events, alongside examining tolerability and the effects of stopping treatment.
Lilly has advanced retatrutide into larger phase 3 trials, which are designed to evaluate the drug in more people and over longer periods. Those studies can test whether the striking weight-loss signal holds up and provide better evidence about benefits and risks. Until such results are available and regulators review them, retatrutide remains an investigational medicine rather than an approved obesity treatment.
Susan Carter serves as a Senior Correspondent for Just Right News, where she leads the network’s comprehensive coverage of Health, Medicine, and Public Policy. With a career dedicated to dissecting the complexities of the American healthcare system, Susan brings a principled perspective to the most pressing debates of the day. Her reporting is characterized by a commitment to individual liberty, fiscal responsibility, and a healthy skepticism of government overreach, making her a vital voice for audiences seeking clarity in an increasingly regulated landscape.
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