Pfizer is to move forward with an oral version of an Ozempic-like drug candidate and drop another, while Eli Lilly has released trial results for a new injectable drug that achieved dramatic results, as rivalry intensifies for a pill version of popular weight-loss drugs.
Pfixer binned one of its experimental pill after patients in studies experienced elevated enzymes that could indicate liver damage, but will continue clinical trials for its other weight-loss pill candidate, danuglipron, which, it said last week, has shown promising results with no evidence of side effects on the liver.
At the same time, reports The Washington Post, Eli Lilly disclosed results from an injectable drug, retatrutide, that demonstrated patients lost 24% of their body weight over 48 weeks – a showing even more dramatic than the most effective drugs on the market, which have helped patients shed 15% of their weight. The findings were published in the New England Journal of Medicine.
Drugs like Ozempic are causing a frenzy among people desperate to shed weight, and among investors watching the potential profits of a medication that could treat masses of Americans who are obese.
While Ozempic and rival drugs are approved by the US Food and Drug Administration only to treat diabetes, they owe their viral fame to their effectiveness in helping people lose weight.
The popularity of this new class of weight-loss medications is already fuelling a clash with insurers over prescriptions for patients who don’t have diabetes, foreshadowing more consequential debates over insurance for pricey drugs that affect millions of Americans.
The drugs mimic a hormone naturally produced by the body, glucagon-like peptide 1. GLP-1 drugs, as they are often called, slow the emptying of the stomach, and suppress appetite.
The most popular ones on the market, including Ozempic, Mounjaro and Wegovy – which is FDA-approved for obesity – are all injectable drugs, and manufacturers are betting there will be even more demand for a pill version.
Pfizer’s decision has investors anxious about whether danuglipron, taken twice daily, will be competitive with other pills that need to be taken only once daily.
A company spokesperson said they were developing a “modified once-daily version” of danuglipron and still believe it has the potential to bring in $10bn a year in sales for both obesity and type 2 diabetes.
Eli Lilly, which also makes Mounjaro, showed in the results last week of its study on an oral GLP-1 drug candidate that people lost 8.6% to 12.6% of their body weight after 26 weeks. It said side effects ranged from mild to moderate.
Novo Nordisk, which makes Ozempic and Wegovy, may be in the lead in developing a weight-loss pill. The company is conducting late-stage trials on a pill candidate using the same active ingredient as its hit injectable drugs, and it reported in May that patients lost 17.4% of their weight over 68 weeks on a once-daily dose.
Study details
Triple–Hormone-Receptor Agonist Retatrutide for Obesity – A Phase 2 Trial
Ania Jastreboff, Lee Kaplan, Juan Frías, Qiwei Wu, Yu Du, Sirel Gurbuz, Tamer Coskun, Axel Haupt, Zvonko Milicevic, Mark Hartman.
Published in the New England Journal of Medicine on 26 June 2023
Abstract
Background
Retatrutide (LY3437943) is an agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and glucagon receptors. Its dose–response relationships with respect to side effects, safety, and efficacy for the treatment of obesity are not known.
Methods
We conducted a phase 2, double-blind, randomised, placebo-controlled trial involving adults who had a body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of 30 or higher or who had a BMI of 27 to less than 30 plus at least one weight-related condition. Participants were randomly assigned in a 2:1:1:1:1:2:2 ratio to receive subcutaneous retatrutide (1 mg, 4 mg [initial dose, 2 mg], 4 mg [initial dose, 4 mg], 8 mg [initial dose, 2 mg], 8 mg [initial dose, 4 mg], or 12 mg [initial dose, 2 mg]) or placebo once weekly for 48 weeks. The primary end point was the percentage change in body weight from baseline to 24 weeks. Secondary end points included the percentage change in body weight from baseline to 48 weeks and a weight reduction of 5% or more, 10% or more, or 15% or more. Safety was also assessed.
Results
We enrolled 338 adults, 51.8% of whom were men. The least-squares mean percentage change in body weight at 24 weeks in the retatrutide groups was −7.2% in the 1-mg group, −12.9% in the combined 4-mg group, −17.3% in the combined 8-mg group, and −17.5% in the 12-mg group, as compared with −1.6% in the placebo group. At 48 weeks, the least-squares mean percentage change in the retatrutide groups was −8.7% in the 1-mg group, −17.1% in the combined 4-mg group, −22.8% in the combined 8-mg group, and −24.2% in the 12-mg group, as compared with −2.1% in the placebo group. At 48 weeks, a weight reduction of 5% or more, 10% or more, and 15% or more had occurred in 92%, 75%, and 60%, respectively, of the participants who received 4 mg of retatrutide; 100%, 91%, and 75% of those who received 8 mg; 100%, 93%, and 83% of those who received 12 mg; and 27%, 9%, and 2% of those who received placebo. The most common adverse events in the retatrutide groups were gastrointestinal; these events were dose-related, were mostly mild to moderate in severity, and were partially mitigated with a lower starting dose (2 mg vs. 4 mg). Dose-dependent increases in heart rate peaked at 24 weeks and declined thereafter.
Conclusions
In adults with obesity, retatrutide treatment for 48 weeks resulted in substantial reductions in body weight
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