Better injections and better pills. It’s official: Eli Lilly appears to be beating Novo Nordisk at the weight loss game.
On Thursday, Lilly announced that its forthcoming GLP-1 pill, called orforglipron, bested Novo Nordisk’s existing oral semaglutide pill in a large head-to-head clinical trial. (Lilly’s injectable GLP-1 drug tirzepatide already beat injectable semaglutide in another head-to-head trial last year.)
Lilly’s pill “outperformed” Novo’s “on every key endpoint we measured, including A1C and weight loss,” lead trial investigator Dr. Julio Rosenstock, an endocrinologist and diabetes and metabolism expert, said in a release.
The trial, which lasted one year and included 1,698 patients with diabetes on three continents, is the latest big win for Lilly, which has been racing ahead of its competitors in developing new and improved formulations of GLP-1 drugs.
Once the breakout star with Ozempic, Novo Nordisk has struggled to come up with a new winner, with its latest results on the new investigational drug CagriSema underwhelming investors earlier this week. If all goes well with the US Food and Drug Administration in the coming months, orforglipron could be available to US consumers by this spring, with prices rivaling a “fancy gym membership,” according to one analyst.
15 to 20 pounds of weight loss and heart health benefits, but more side effects
The drug improved blood sugar control and also led to weight loss and heart health benefits.
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Novo Nordisk’s existing GLP-1 pill, Rybelsus, was approved by the FDA for the treatment of diabetes in 2019. It’s a once-daily formulation that must be taken first thing in the morning on an empty stomach, with only a small amount of water.
Lilly’s new orforglipron would have none of those restrictions. It can be taken at any time of day, with or without food. It’s also looking more powerful than Rybelsus, in part because the dosages tested were higher.
In the new trial, published in The Lancet on Thursday, patients on 7 to 14 milligrams of Rybelsus lost, on average, between 8 and 11 pounds, while patients on 12 to 36 milligrams of orforglipron lost an average of 15 to 20 pounds, roughly the same level of weight loss that people with diabetes tend to achieve when taking Ozempic. In addition to the blood sugar control and weight loss benefits, orforglipron takers had greater improvements in cholesterol levels, blood pressure readings, and triglycerides than Rybelsus users.
“Overall, the field is moving toward treatments that meaningfully improve weight, blood sugar, and cardiovascular risk at the same time,” Dr. Naveed Sattar, a professor of cardiometabolic medicine at the University of Glasgow, who was not involved in this study, said in a release. “These more holistic approaches, which also benefit patient well-being, are likely to offer the greatest benefits for people living with type 2 diabetes.”
The downside? A stronger drug regimen means more side effects. Roughly 10% of patients on the highest dose of orforglipron quit this trial early, complaining of gastrointestinal issues including nausea, diarrhea, and indigestion. Only about 5% of people on the highest dose of Rybelsus quit because of side effects like that.
In a statement to Business Insider, Novo Nordisk pointed to its higher-dose Wegovy pill and forthcoming Ozempic pill, which are both more powerful than Rybesus for weight loss, and rival the efficacy of orforglipron.
Orforglipron could hit shelves in 2026, and Eli Lilly has already ramped up its production
Eli Lilly has been building out its manufacturing capacity, racing to meet demand for GLP-1s.
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Eli Lilly told Business Insider that the company is already manufacturing orforglipron pills in Alabama, Texas, Puerto Rico, and the Netherlands to ensure it can meet demand ASAP if and when the drug is approved for use in the US. Lilly is betting that approval could come before the summertime, and federal filings show an initial approval for obesity could come as early as April 10.
Though a daily pill requires more obedience than a weekly shot, it has a few advantages. First, it’s likely to be much cheaper. Deutsche Bank’s director of biopharma equity research, James Shin, said it would be comparable to buying a “fancy gym membership.” As part of a November agreement with the US government, Eli Lilly will be selling orforglipron through its LillyDirect website for $145-399 out of pocket (far cheaper than the $1,000+ price tags on Ozempic, Wegovy, Mounjaro, and Tirzepatide). Clinical trials have also shown that orforglipron can help patients who’ve already been on an injectable GLP-1 maintain their weight loss if they choose to stop taking the drug, acting as a maintenance medication.
Second, since this is a small molecule, it doesn’t need to be refrigerated, a huge win for global distribution and manufacturing.
“There are more than one billion people across the globe that are suffering from obesity,” Patrik Jonsson, the president of Lilly International, previously told Business Insider. “There is no way that we can meet those demands with injectable treatments today.”
This story has been updated with a statement from Novo Nordisk, and new pricing and manufacturing information for orforglipron from Eli Lilly.
