Experimental Eli Lilly Weight Loss Drug Orforglipron Shows Promise in Clinical Trials

There’s a new GLP-1 drug currently in development by Eli Lilly & Co, also the manufacturer of Mounjaro® (tirzepatide), that has recently demonstrated some promising results in clinical trials. 

The experimental weight loss pill, orforglipron, completed a midstage trial with 75% of study participants achieving a weight reduction of at least 10% after 36 weeks. The drug belongs to the GLP-1 receptor agonist class and exhibited similar side effects to other GLP-1s on the market (such as nausea and constipation). 

These findings were published in the New England Journal of Medicine and presented at the American Diabetes Association conference in June 2023.

Overview of orforglipron vs. other available GLP-1s 

Most of the currently-approved GLP-1 weight loss medications, like Novo Nordisk's Wegovy® (semaglutide), are administered as once-weekly injections. Other drugs in the same class, such as Ozempic® (semaglutide) and Mounjaro® (tirzepatide), are approved for type 2 diabetes but have been used off-label for weight loss. 

Unlike Ozempic® and Mounjaro®, which are delivered via self-injection, orforglipron is a once-daily pill. This is a benefit for those who may feel intimidated by self-injection or have a fear of needles, eliminating certain barriers to entry. 

The mean weight loss of 7.1 to 12.3% achieved with orforglipron over the course of the 36-week trial was significant because it improved cardiometabolic health by lowering systolic blood pressure and showing beneficial changes in cholesterol levels. 

Dr. Nadia Ahmad, overseeing the drug's development at Lilly, emphasized the importance of offering patients different treatment options. The trial did not show any plateauing of weight loss at the 36-week mark, and further studies are planned to evaluate its long-term efficacy.

Orforglipron clinical trial details

The trial involved 272 participants with obesity or overweight and weight-related health conditions. Four different doses of orforglipron were tested, ranging from 12 to 45 milligrams, along with a placebo group. Weight loss at 36 weeks varied between 9.4% and 14.7%, compared to 2.3% in the placebo group. Participants also experienced positive effects on triglyceride and cholesterol levels, as well as systolic blood pressure.

Common side effects of orforglipron included nausea, constipation, vomiting, and diarrhea. Most side effects were mild to moderate, occurring as participants gradually increased their dosage. However, between 10% and 17% of participants discontinued the drug due to these side effects and, thus far, it appears that GI side effects may be more prominent with orforglipron versus injectable GLP-1 medications. 

One limitation of the study worth noting was the lack of diversity among participants, with 91% identifying as white. The manufacturer acknowledged the importance of achieving better representation in clinical trials and confirmed their intention to improve diversity in future studies.

Potential market impact and other weight loss drugs in development

Eli Lilly's orforglipron is one of several experimental weight loss drugs aiming to enter the market. Novo Nordisk recently reported promising results with a new, higher-dose (50mg) version of semaglutide—the same active ingredient that’s found in injectibles Wegovy® and Ozempic®—which achieved 15% weight loss over 68 weeks. Pfizer has also shown interest in developing oral GLP-1 drugs; however, one was discontinued due to potential interactions with other medications and elevated liver enzymes.

While orforglipron's midstage trial results are promising, the drug still needs to undergo larger-scale phase 3 trials before it can be approved for market use. Despite the potential competition, the development of alternative weight loss options, such as daily pills like orforglipron, provides patients with greater flexibility and choice in managing chronic weight conditions.

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