November 28, 2023

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

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

“This amount of weight loss from a single medication 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.

The results of the phase 2 clinical trial for the once-weekly injected medicine, retatrutide, were published June 26 in The New England Journal of Medicine, and presented this month at the American Diabetes Association scientific conference in San Diego.

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

Researchers also found that the most common side effects of retatrutide were nausea, diarrhea, vomiting and constipation — similar to what occurs with approved drugs in this class, including Ozempic, Wegovy and Mounjaro.

Retatrutide mimics the action of three hormones — GLP-1, GIP and glucagon — which earned it the nickname “triple G.” These hormones help regulate blood sugar, slow the emptying of the stomach (to increase a sense of fullness) and decrease appetite.

Dr. Dan Skovronsky, Eli Lilly’s chief scientific and medical officer, said in a statement that this triple action of the drug “may be one of the reasons retatrutide showed this level of weight reduction.”

Novo Nordisk’s semaglutide (FDA-approved for weight loss as Wegovy) mimics just one hormone, GLP-1; half of participants in a phase 3 clinical trial of this drug experienced weight loss of 15% or more.

Lilly’s tirzepatide (FDA-approved for diabetes as Mounjaro, and awaiting approval for treatment of obesity) mimics both GLP-1 and GIP, and produced weight loss in a phase 3 trial of up to 23%.

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

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

In addition to people on the highest dose of retatrutide averaging 24% weight loss over 48 weeks, over one-quarter of those participants experienced weight loss of at least 30%.

“This is an unusually high magnitude of efficacy as compared with findings in clinical trials of other anti-obesity agents,” the researchers wrote. However, they pointed out that this amount of weight loss has been seen with bariatric–metabolic surgery.

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

“We used to consider 5-10% total body weight loss a big 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 it’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 the use of a lower starting dose,” the researchers wrote.

Researchers also saw increases in heart rate in people taking retatrutide, which occurred up to week 24, followed by a decline after that point.

Some people also experienced “altered or enhanced skin sensation,” although not severe enough for them to stop taking the drug.

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

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

By the end of the trial, participants taking retatrutide were continuing to lose weight, the researchers wrote, which suggests that people might lose even more in Eli Lilly’s longer-duration phase 3 trial that is currently underway.

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

“[The] phase 2 data have given us confidence to further explore the potential of retatrutide in phase 3 trials that will look beyond weight reduction and focus on treating obesity and its complications comprehensively,” Skovronsky said in the statement.

Saunders said based on the results of the phase 2 trial, she anticipates that retatrutide will outperform tirzepatide in the phase 3 trial.

In spite of the success of these newer anti-obesity medications, Saunders cautions against people using the drugs without additional support from a healthcare team.

“Obesity isn’t a simple disease with a simple solution,” she said. “Effective treatment of obesity must include a comprehensive evaluation, a personalized treatment plan, and education and support to maximize weight loss, minimize potential side effects and ensure long-term weight maintenance.”

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

“Drastic weight loss, regardless of how you lose the weight, can be quite overwhelming,” she told Healthline. “For some, it could impact their body image, relationships, mood, etc.”

She also thinks it is important for people to be properly assessed by a doctor before being prescribed an anti-obesity medication.

“I would be concerned about someone with a history of an eating disorder being prescribed these medications 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 such as 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 early as possible,” said Goldman.


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