Drawing Closer to a Once-Daily Oral GLP-1 That Works
The news in obesity research these days is so full of headlines about a multitude of new medicines in development that it is easy to lose count. All too often, these are early stage or even pre-clinical notions of a potential treatment. So yesterday, it was good news indeed to hear that a once-daily oral GLP-1 is coming really close to being an actual new medicine.
In the first of a whole array of phase three studies, orforglipron worked well in patients with both type 2 diabetes and obesity.
Comparable to Semaglutide?
These are topline results, released by Lilly in advance of their full presentation at the upcoming Scientific Sessions of the American Diabetes Association. So we don’t have the full picture we will get from a peer-reviewed publication. But we have no reason to doubt the accuracy of this topline.
What we are seeing is improvements in blood sugar that are similar to the improvements with semaglutide (Ozempic) after a similar duration of treatment – 40 weeks. The study tested three different doses of orforglipron, 3, 12, and 36 mg versus placebo. A total of 559 individuals enrolled in the study. After 40 weeks, A1C came down from a baseline of 8.0 by 1.3 to 1.6 points. Patients lost between five and eight percent of their body weight, with the greatest weight loss at the highest dose. The safety and tolerability profile was similar to other drugs in this class.
Admittedly, the percent weight loss is not stunning, but remember this was a diabetes study. These results are similar to the weight loss seen with semaglutide in treatment for diabetes. We will have to wait for phase three results in obesity to get a definitive picture for its efficacy. In phase two, the results for obesity were similar to what semaglutide delivers.
Importantly, Lilly noted that “no hepatic safety signal was observed.” This is important because Pfizer canceled the development of danuglipron earlier this week due to a hepatic safety issue. It was a similar oral GLP-1 agonist for oral use. Drug development is a risky business.
Submission to FDA for Obesity This Year
So yes, this once-daily oral GLP-1 is drawing closer to being a real medicine that may help many millions of people. Lilly said they plan to submit it for an obesity indication by the end of this year. The submission for diabetes will come next year. Plus, trials are ongoing to evaluate its benefits for obstructive sleep apnea and hypertension in persons with obesity.
On top of all that, remember that orforglipron is a relatively small molecule – much simpler to make than complex peptides like semaglutide or tirzepatide. That will create cost advantages and advantages for scale of manufacturing.
For sure, orforglipron is an important new drug for diabetes and obesity, and it is drawing closer to market. This is good news.
Click here for free access to reporting on this news from the New York Times and here for reports from the Wall Street Journal. For the announcement from Lilly, click here.
Tablet and Water Glass, photograph by Ted Kyle / ConscienHealth
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April 18, 2025
