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New Generation of Weight-Loss Drugs: Injection vs. Pills


Patients looking to shed pounds now have a choice in how to take the new generation of weight-loss drugs called incretins. While pills may seem convenient and cheap, injections result in more significant weight loss.

At the annual science meeting of the American Diabetes Association, Eli Lilly reported the first results for the most powerful incretin tested thus far, retatrutide. In a Phase 2 study published in The New England Journal of Medicine, patients lost an average of over 24% of their body weight after 11 months of weekly injections. This is equivalent to around 58 pounds on average and beats the 21% weight loss averaged by Lilly’s Mounjaro, another incretin currently approved only for patients with Type 2 diabetes.

Interestingly, weight loss did not plateau when the retatrutide study ended. Longer use may yield even greater results, says Ania Jastreboff, a professor at Yale School of Medicine and one of the investigators.

In addition to weight loss, patients in the retatrutide study also showed improvements in waist circumference, blood pressure, insulin measures, and cholesterol levels. The safety profile of retatrutide was similar to other incretin products, and only 15% of those on the highest dose dropped out because of gastrointestinal discomfort.

Eli Lilly plans to move forward with Phase 3 trials for retatrutide, and shares of Lilly were up by 1.8% in premarket trading Tuesday.

New Weight Loss Pills Developed by Major Pharmaceutical Companies

Several pharmaceutical companies have been developing new weight loss pills. Eli Lilly and Company developed an experimental pill called orforglipron, which allows obese patients to lose up to 14.7% of their body weight in nine months. Diabetes patients can also benefit from the drug, losing up to 10% of their weight and experiencing improved diabetes measures. These weight loss results are comparable to approved drugs, Wegovy and Ozempic from Novo Nordisk, which are once-weekly injectables. Lilly’s stock went up by 2.9%, while Novo’s shares slightly decreased by 0.4%.

Novo Nordisk has an incretin pill on the market called Rybelsus. More recently, the Danish company reported a higher dose of the active ingredient in Rybelsus, which resulted in a 15% weight loss for patients after 16 months of treatment.

Pfizer has also been working on developing two weight-loss pills. Unfortunately, one of the experimental pills was discontinued, but danuglipron, the other, continues to be tested. In a Phase 2 trial among diabetics, danuglipron helped patients lose 5% of their weight after four months on the highest dose. Pfizer is currently working on a once-daily version of the drug. However, the announcement about discontinuing one of its pills resulted in Pfizer’s stock decreasing by 3.7% to close at $36.89.

The Future of Weight-Loss Drugs

Incretins are a type of hormone that can affect our appetite by sending signals to cells in our gut and brain. Mimicking the effects of incretins is the key to the effectiveness of new weight-loss drugs such as Novo Nordisk’s Ozempic and Wegovy, and Eli Lilly’s Mounjaro and retatrutide.

Of these drugs, only injectable Wegovy has FDA approval as a weight-loss drug but its coverage by insurance providers has been limited so far. However, results from the Select study by Novo Nordisk, due to be released next month, could change all that. The study followed 17,600 patients to see if weight loss from Wegovy could help them avoid major cardiac events like a heart attack or stroke.

According to Guggenheim analyst Seamus Fernandez, the Select study should show a reduction of over 10% in cardiac events among patients who lost weight on Wegovy. This could be the turning point for insurance reimbursement and the stock value of Novo Nordisk’s drug and Eli Lilly’s Mounjaro.

Stay tuned for next month’s results and watch the future of weight-loss drugs unfold.

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