Eli Lilly obesity pill beats Novo Nordisk drug in diabetes trial

Eli Lilly on Wednesday said its experimental pill outperformed Novo Nordisk‘s own oral drug in the first head-to-head study comparing the two medicines in patients with Type 2 diabetes. 

The late-stage study comes as Eli Lilly’s pill inches closer to becoming another needle-free alternative in the blockbuster market for GLP-1s, without dietary restrictions. But it may be too soon to establish a clear winner in the pill space, as there is no data comparing Eli Lilly’s drug with a higher dose of Novo Nordisk’s pill in patients with obesity.

Eli Lilly said its pill, orforglipron, was superior at the trial’s main goal of lowering blood sugar levels at 52 weeks compared with Novo Nordisk’s oral semaglutide. The highest dose of orforglipron helped lower hemoglobin A1c — a measure of blood sugar levels — by 2.2% compared with 1.4% with Novo Nordisk’s pill. 

The highest dose of Eli Lilly’s drug also helped patients lose an average of 9.2% of their weight, or 19.7 pounds, compared with 5.3% weight loss, or 11 pounds, with Novo Nordisk’s pill. Orforglipron’s weight loss was 8.2% when analyzing all patients regardless of discontinuations, while oral semaglutide’s was 5.3%. 

The results suggest an up to 36-milligram dose of Eli Lilly’s pill may be more effective at treating diabetes patients than an up to 14-milligram dose of oral semaglutide, which is already approved under the name Rybelsus for Type 2 diabetes.

“For the majority of patients, this could be the main medicine that they need to control their Type 2 diabetes as well as their obesity,” Eli Lilly Chief Scientific Officer Dan Skovronsky said in an interview.

Dr. Michael Weintraub, an endocrinologist at NYU Langone Diabetes & Endocrine Associates, said orforglipron’s management of blood sugar levels is “quite impressive not only compared to other oral Type 2 diabetes medications but all Type 2 diabetes medications including injectables.”

The company on Wednesday said it expects to apply for approval of orforglipron for the treatment of Type 2 diabetes in 2026. Eli Lilly hopes to launch its pill globally “this time next year,” CEO David Ricks told CNBC in early August.

Eli Lilly and Novo Nordisk are vying for a greater share of the booming market for GLP-1s, which some analysts say could be worth around $100 billion by the 2030s. The space is eager for more convenient options that could ease the supply shortfalls and access hurdles created by the pricey weekly injections currently dominating it.

Oral GLP-1s could grow to be worth $50 billion of that total, according to some analyst estimates.

But it’s less clear how Eli Lilly’s pill compares with higher doses of oral semaglutide, especially in patients who are overweight or have obesity without diabetes. Novo Nordisk expects U.S. regulators to approve a higher 25-milligram dose of its pill for the treatment of obesity by the end of the year, and has also studied a 50-milligram dose of the drug in a phase three trial.

Weintraub said comparing the 36-milligram dose of Eli Lilly’s pill to oral semaglutide at a lower dose than what may be approved in the future “is short-changing semaglutide.” He added that patients with diabetes typically lose less weight than those without the condition, so the closer to 15% weight loss that oral semaglutide has shown in people with obesity is “certainly not expected” in a study on Type 2 diabetes patients.

Because the trial showed Eli Lilly’s pill was better at reducing blood sugar and weight only when compared with specific lower doses of oral semaglutide, “there are several orders that kind of slow the roll a little bit as we look at the results and get kind of excited,” said Dr. Jaime Almandoz, medical director of the Weight Wellness Program at UT Southwestern Medical Center.

Almandoz said it’s “a little too early to say that one is kind of a leader in the class” of drugs. But he said head-to-head data is helpful as doctors determine which pill may be a better fit for certain diabetes patients. 

Detailed results on the trial will be presented at a medical meeting and published in a peer-reviewed journal.

The company can’t run studies on medicines from competitors that aren’t approved yet, Skovronsky noted. But he said he’s confident Eli Lilly’s pill can beat higher doses of oral semaglutide in head-to-head trials. 

Skovronsky likened orforglipron’s efficacy to that of “new-generation” injectable GLP-1s. He appears to be referring to Eli Lilly’s blockbuster diabetes injection Mounjaro and Novo Nordisk’s competing shot Ozempic.

Meanwhile, Skovronsky said oral semaglutide “is really performing at…