The strongest weight loss drug in history? Eli Lilly's "Triple G" weight loss drug averages a weight loss of 23.7%, exceeding expectations, and can also cure knee pain

Stronger than the strongest Zepbound weight loss injection? Eli Lilly's new obesity drug retatrutide has demonstrated the strongest weight loss effect to date in late-stage clinical trials, while significantly alleviating knee arthritis pain, providing a key weapon for this pharmaceutical giant to consolidate its leading position in the obesity market, which is expected to reach hundreds of billions of dollars.

On December 11, Eli Lilly's latest data revealed that during the 68-week trial period, obese patients with knee arthritis receiving the highest dose treatment lost an average of 23.7% of their weight. This result exceeded Wall Street's previous expectations of 20%-23%, with some patients even voluntarily withdrawing from the trial due to excessive weight loss.

The drug also achieved another main goal of the trial, with average knee osteoarthritis pain reduced by 62.6%, and more than one-eighth of patients completely relieved of knee pain by the end of the trial. Following the announcement of the results, Eli Lilly's stock price rose more than 3% in pre-market trading, and as of the time of writing, it was up 0.6%.

This is the first disclosure of late-stage clinical data for retatrutide. The drug employs a triple hormone mechanism, which is different from the action mechanism of existing injectables, resulting in more significant efficacy.

Reports indicate that in the weight loss and diabetes drug market, which is expected to reach $100 billion in the 2030s, Eli Lilly is betting on retatrutide to become a new growth pillar following the Zepbound weight loss injection and the upcoming oral medication, to maintain its market share advantage over Novo Nordisk.

Efficacy Exceeds Expectations, Side Effects Lead to Withdrawals

The weight loss effect of retatrutide shows significant differences in analytical methods.

Data shows that when including all participants (including those who discontinued treatment), the highest dose group lost an average of 23.7% of their weight; if only counting patients who adhered to the medication, the weight loss increased to 28.7%. In contrast, the active ingredient in Eli Lilly's existing weight loss injection Zepbound, tirzepatide, helped obese patients lose an average of up to 22.5% in late-stage studies.

According to reports, BMO Capital Markets analyst Evan Seigerman stated before the results were announced that his baseline expectation was for a weight loss of 20%-23% and at least a 50% reduction in knee pain. Actual data showed that based on widely used survey questionnaires, patients experienced a 62.6% reduction in knee pain.

However, side effects led to approximately 18% of patients receiving the highest dose treatment discontinuing the medication, while the rate in the placebo group was only 4%.

Eli Lilly stated that the withdrawal rate is "highly correlated" with patients' initial BMI, including cases of discontinuation due to "feeling excessive weight loss." In the highest dose group, about 43% of patients experienced nausea, 33% experienced diarrhea, and 20.9% experienced vomiting.

More than one-fifth of patients also experienced abnormal sensations—a discomforting nerve sensation, but Eli Lilly stated that this symptom is usually mild and rarely leads to discontinuation

Triple Mechanism Establishes Technical Advantage

Retatrutide is known as a "triple G" drug, which works by mimicking GLP-1, GIP, and glucagon, three hormones that regulate hunger, rather than acting on just one or two hormones like existing therapies. This mechanism appears to have a stronger effect on appetite and satiety.

Kenneth Custer, President of Eli Lilly's Cardiometabolic Health Division, stated in a statement that the company believes retatrutide "may become an important option for patients with significant weight loss needs and certain complications (including knee osteoarthritis)."

The study, named TRIUMPH-4, does not solely focus on weight loss, which means that other trials specifically designed for weight loss outcomes may yield different or higher data. Eli Lilly expects to announce the results of seven additional Phase III clinical trials for the drug by the end of 2026.

Competitors Accelerate Catch-Up

Eli Lilly currently dominates the obesity drug market, with its Zepbound becoming the most popular weight loss medication. The company is accelerating the development of next-generation drugs that are more effective, easier to take, or have fewer side effects to maintain its competitive edge.

Some analysts predict that the market for weight loss and diabetes drugs could reach approximately $100 billion by the 2030s. Eli Lilly is currently unclear when retatrutide will enter the market, but the drug is crucial for maintaining the company's majority share in this rapidly growing market.

Trials also showed that both the 9 mg and 12 mg doses reduced cardiac disease markers and blood pressure. Eli Lilly's Chief Scientific Officer Daniel Skovronsky stated in an investor conference call last October:

"Not all patients need this potential level of extreme efficacy; we believe retatrutide may be best suited for patients with very high BMI or obesity-related complications who require significant weight loss."

Reportedly, competitor Novo Nordisk's newly acquired drug is a potential competitor to retatrutide, as it also employs a triple approach to promote weight loss and regulate blood sugar. However, Novo Nordisk's therapeutic drug is in an earlier stage of development, meaning it will take several years to bring to market.

Last year, after Novo Nordisk's experimental drug CagriSema fell short of expectations, the company's stock price plummeted to a record low. The drug helped patients lose an average of 20.4%, below Novo Nordisk's promised 25%.

This highlights the high risks of next-generation compounds: in the obesity market, which is expected to reach $100 billion by 2030, any fluctuations in clinical data could trigger severe market reactions