New Eli Lilly drug leads to 24% weight loss in study

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Eli Lilly is studying a new weight loss drug. Cristina Arias/Cover/Getty Images
  • A new drug under development led people to lose about 25% of their body weight in a recent study.
  • The drug called retatrutide is a weekly injection.
  • The researchers also found that the most common side effects of retatrutide were nausea, diarrhea, vomiting and constipation.

A new drug developed by Eli Lilly & Co. has helped people lose an average of about 24 percent of their body weight over 48 weeks while taking the highest dose, surpassing results seen in trials of other anti-obesity drugs.

This amount of weight loss from a single drug is truly mind-blowing, said obesity expert Dr. Katherine H. Saunders, co-founder of Intellihealth and a faculty member at Weill Cornell Medicine. She was not involved in the research.

Results from the Phase 2 clinical trial for the once-weekly injected medicine, retatrutide, were published June 26 in The New England journal of medicineand presented this month at the American Diabetes Association’s scientific conference in San Diego.

Phase 2 trials are conducted in a small group of participants and provide data on how a drug works and the ideal dosage. Larger studies are needed before the drug can be approved by the Food and Drug Administration (FDA) for clinical use.

The researchers also found that the most common side effects of retatrutide were nausea, diarrhea, vomiting and constipation similar to those that occur with approved drugs in this class, including Ozempic, Wegovy and Mounjaro.

Retatrutide mimics the action of three hormones GLP-1, GIP and glucagon that have earned it the nickname triple G. These hormones help regulate blood sugar, slow stomach emptying (to increase feelings of fullness) and decrease stomach appetite.

Dr. Dan Skovronsky, chief scientific officer and Eli Lilly physician, said in a statement that this triple action of the drug could be one reason retatrutide has shown this level of weight reduction.

Novo Nordisks semaglutide (FDA-approved for weight loss like Wegovy) only mimics one hormone, GLP-1; half of the participants in a phase 3 clinical study of this drug experienced weight loss of 15% or more.

Lillys tirzepatide (FDA-approved for diabetes like Mounjaro and pending approval for the treatment of obesity) mimics both GLP-1 and GIP and produced weight loss in a Phase 3 study of up to 23%.

In the retatrutide study, researchers enrolled 338 people with a body mass index (BMI) of 30 or higher; or a BMI between 27 and 30, with at least one weight-related health condition.

The BMI is a measurement to assess whether someone is obese (30 or more), overweight (25-29.9), or underweight (less than 18.5). It is not always an accurate assessment of body fat, especially for some racial/ethnic or other groups.

In addition to those taking the highest dose of retatrutide, with an average weight loss of 24% over 48 weeks, over a quarter of these participants experienced at least 30% weight loss.

This is an unusually high magnitude of efficacy compared with clinical trial results of other anti-obesity agents, the researchers wrote. However, they did point out that this amount of weight loss was seen with bariatric metabolic surgery.

Everyone in the highest dose group experienced at least 5% weight loss, a higher rate than seen in the phase 3 study for semaglutide: 86% of participants in that study lost this amount of weight .

We considered 5 to 10 percent total body weight loss a great success, Saunders told Healthline, because this amount of weight loss is associated with significant improvements in weight-related health complications.

However, weight loss greater than 15% is now achievable, so that’s the new benchmark, she said.

The most common side effects experienced by people taking retatrutide were nausea, diarrhea, vomiting and constipation, which were more common at higher doses of the drug.

These were partially reduced by use of a lower starting dose, the researchers wrote.

The researchers also saw increases in heart rate in people taking retatrutide, which occurred through week 24, followed by a decline after that point.

Some people have also experienced altered or improved skin sensation, though not severe enough to make them stop taking the drug.

In addition to weight loss, people taking retatrutide have experienced other benefits, including a decrease in blood pressure with some people being able to stop taking a blood pressure-lowering drug.

Nearly three-quarters of people who had prediabetes at the start of the study returned to normal blood sugar levels after 48 weeks compared with one-fifth of people taking the inactive placebo.

By the end of the study, participants taking retatrutide continued to lose weight, the researchers wrote, suggesting that people may be losing even more in Eli Lilly’s Phase 3 study currently underway.

This study will examine the safety of retatrutide and its efficacy for chronic weight management, obstructive sleep apnea and knee osteoarthritis.

[The] The Phase 2 data gave us confidence to further explore retatrutide’s potential in Phase 3 studies that will look beyond weight reduction and focus on the comprehensive treatment of obesity and its complications, Skovronsky said in the statement.

Saunders said that based on the Phase 2 study results, he expects retatrutide to outperform tirzepatide in the Phase 3 study.

Despite the success of these new anti-obesity drugs, Saunders cautions against people using the drugs without the additional support of a healthcare team.

Obesity is not a simple disease with a simple fix, she said. Effective obesity treatment must include a comprehensive evaluation, individualized treatment plan, education, and support to maximize weight loss, minimize potential side effects, and ensure long-term weight maintenance.

Rachel Goldman, PhD, assistant professor of psychiatry at NYU Grossman School of Medicine and consultant for online health company Ro, agrees that people losing weight should get the support they need, including nutrition and counseling psychology before starting the treatments.

The drastic weight loss, no matter how you lose weight, can be pretty overwhelming, she told Healthline. For some, it might impact body image, relationships, mood, etc.

He also believes it is important for people to be properly evaluated by a doctor before being prescribed an anti-obesity drug.

I would be concerned about someone with a history of eating disorders being prescribed these drugs without proper counseling and a plan in place, she said.

While anti-obesity medications can help people lose weight over the course of a year or two, lifestyle changes like eating healthier, being more physically active and managing stress can also support long-term health.

Individuals will be healthier and more successful [with weight loss]if they start implementing health behavior changes as soon as possible, Goldman said.

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