New data from an experimental drug being developed by Eli Lilly & Co. raises an intriguing question about obesity treatments: How low can the weight loss go?
For a subset of patients in a mid-stage study of retatrutide, the answer seems to be very, very low. Most people in a study published this week in the New England Journal of Medicine lost nearly a quarter of their body weight, with a subset shedding more than 30% after 48 weeks on a high dose of the drug. The doctors running the trial said some people had yet to “plateau,” suggesting they might shed even more pounds.
These numbers are, frankly, mind-blowing. It was only two years ago that Novo Nordisk rewrote the narrative on weight-loss drugs, which for decades had offered very little benefit and too many side effects, when it showed that people taking Wegovy could lose roughly 15% of their body weight. Then, last year, observers were astonished when Lilly’s tirzepatide elicited nearly 20% weight loss in a Phase 3 study. Now, Lilly’s latest drug has set the bar for weight loss even higher.
Of course, the retatrutide data — both its efficacy and safety — need to be confirmed in a larger trial. But for people with a BMI of 35 or more, that potential level of weight loss “could virtually eliminate the need for bariatric surgery,” BMO Capital Markets analyst Evan Seigerman said in a note to investors.
It’s clear that we’re in entirely new territory when it comes to manipulating our metabolism. Scientists are increasingly learning how to harness the intricate interplay between our brain and our gut. And Lilly’s drug is providing early clues about what that could eventually mean for society’s health.
Retatrutide’s performance seems to come from its unique way of tinkering with the hormones that control our appetite. Like Wegovy, retatrutide mimics a hormone called GLP-1, which helps to control blood sugar levels by signaling the secretion of insulin after eating. And like tirzepatide, the drug also potently mimics a second hormone involved with insulin secretion called GIP. But retatrutide also stimulates a third hormone, the glucagon receptor, which unlike GLP-1 and GIP is found in the liver — an addition that could be driving some of the drug’s benefits.
Indeed, significant weight loss isn’t the only reason people are excited about the drug’s early data. As I’ve written in the past, obesity medicines still need to prove they can have a positive impact on patients’ health. On that front, Lilly’s drug is already hitting some key metrics. For example, treatment with retatrutide led to a 20% reduction in LDL, or “bad” cholesterol, double the improvement typically seen with other GLP-1 drugs.
And higher doses of retatrutide lowered levels of fat in the liver by over 80%. Liver disease is so common in people with Type 2 diabetes that the American Diabetes Association recently recommended that all Type 2 diabetics be screened for it. And a small portion of people with nonalcoholic fatty liver disease go on to develop a more serious condition called NASH, where accumulation of scar tissue eventually prevents the liver from properly functioning.
The hope is that the right weight-loss drug could tackle obesity, diabetes and liver disease all at once. While larger studies still need to be run, it’s looking a lot like retatrutide might be the one to take on that triple threat.
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(Lisa Jarvis is a Bloomberg Opinion columnist covering biotech, health care and the pharmaceutical industry. Previously, she was executive editor of Chemical & Engineering News)
