Eli Lilly’s next generation obesity drug has delivered the highest weight loss yet in a late stage trial while reducing knee arthritis pain, clearing the first of several upcoming studies on the weekly injection.
CNBC reports that the highest dose of the drug helped patients with obesity and a type of knee arthritis lose an average of 23.7% of their body weight at 68 weeks, when analysing all participants, including those who discontinued treatment.
When evaluating only patients who stayed on the drug, the highest dose delivered 28.7% weight loss on average.
The company said some patients lost so much weight that they decided to drop out of the trial.
Experts aid Eli Lilly appears to be positioning the drug strategically for people with severe obesity, or a body mass index above 35 or 40, noting noted that the company said 84% of patients in the trial had a BMI above that number in the trial.
It is the first late-stage data on retatrutide, which works differently from existing injections and appears to be more effective. Eli Lilly is betting big on retatrutide as the next pillar of its obesity portfolio after its weight loss injection Zepbound and its upcoming pill.
But it’s still unclear when the drug could enter the market.
It’s a critical part of the company’s plan to maintain its market share majority over Novo Nordisk in the booming market for weight loss and diabetes drugs. Some analysts estimate the segment could be worth about $100bn by the 2030s.
Retatrutide also met the trial’s other main goal of reducing pain from knee osteoarthritis – a common condition that wears down the joint’s cartilage and leads to pain and stiffness – by up to 62.6% on average when analysing all patients, based on a widely-used survey.
More than one in eight patients who took the drug were completely free from knee pain by the end of the trial, Eli Lilly said.
One concern with current weight loss drugs is that they can lead to the loss of lean muscle mass. But the company said the results show that in adults with severe obesity, physical function can be improved with retatrutide.
“Retatrutide could become an important option for patients with significant weight loss needs and certain complications, including knee osteoarthritis,” said Kenneth Custer, president of Lilly Cardiometabolic Health.
Roughly 18% of patients on the highest dose of the drug stopped treatment due to side effects, compared with 4% of those in the placebo group. Eli Lilly said those dropout rates were “highly correlated” to patients’ starting body mass index and included discontinuations due to “perceived excessive weight loss”.
Among those with a BMI of 35 or higher who took highest dose, 12% stopped treatment. That number is closer to the dropout rates seen in trials on its weight-loss drug Zepbound and Novo Nordisk’s obesity injection Wegovy.
Around 43% of patients on the highest dose experienced nausea, while roughly 33% and 20.9% had diarrhoea and vomiting, respectively. More than one in five patients on the highest dose also experienced dysesthesia, which is an unpleasant nerve sensation.
The company said it was generally mild for patients and rarely led to them discontinuing treatment.
The study, called TRIUMPH-4, didn’t solely focus on weight loss, meaning that other trials specifically designed for that outcome could produce different or higher results.
Eli Lilly expects to report findings from seven additional phase three trials on the drug by the end of 2026.
Dubbed the “triple G” drug, retatrutide works by mimicking three hunger-regulating hormones – GLP-1, GIP and glucagon – rather than just one or two like existing treatments. That appears to have more potent effects on a person’s appetite and satisfaction with food than other treatments.
Tirzepatide, the active ingredient in Zepbound, mimics GLP-1 and GIP. Novo Nordisk’s semaglutide, the active ingredient in Wegovy, mimics only GLP-1.
Higher doses of tirzepatide helped patients with obesity lose roughly 20.9% of their body weight on average in late-stage studies, when analysing all patients regardless of discontinuations.
As Eli Lilly establishes an edge in the space, its chief rival, Novo Nordisk, is racing to catch up. In March, Novo Nordisk said it agreed to pay up to $2bn for the rights to an early experimental drug from the Chinese pharmaceutical company United Laboratories International.
Novo Nordisk’s newly acquired drug is a clear potential competitor to retatrutide because it similarly uses a three-pronged approach to promoting weight loss and regulating blood sugar.
But Novo Nordisk’s treatment is much earlier in development, meaning it will take several years before it reaches patients.
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