Drugmaker Eli Lilly said Thursday that an experimental pill form of popular GLP-1 medications helped people with type 2 diabetes lose an average of nearly 8% of their body weight after 40 weeks and lowered their A1C levels.
Lilly, which makes the injectable drugs Zepbound to treat obesity and Mounjaro and Trulicity to treat diabetes, is among several companies chasing an effective pill form of GLP-1s. The only such pill available so far comes with strict diet restrictions.
Lilly’s announcement comes on the heels of an announcement from Pfizer, which said Monday that it was ending development of its daily pill treatment for obesity. A patient in the clinical trial had a possible liver injury that was no longer a problem once they stopped taking that drug, Pfizer said.
In 2020, the US Food and Drug Administration approved Novo Nordisk’s Rybelsus for treatment of type 2 diabetes, but it has to be taken on an empty stomach. Some doctors also report that Rybelsus may not be as effective as injections yet still comes with side effects.
Lilly says that no such diet restrictions are needed with its experimental oral medication, orforglipron, and that it’s the first drug of its kind to complete a Phase 3 trial.
the Indianapolis company said that in a study of more than 550 people, orforglipron reduced weight by an average of 16 pounds (7.9%) among people who had type 2 diabetes with inadequate glycemic control with diet and exercise alone, and who were using the highest dose of the medication. The participants were still losing weight by the end of the 40-week trial.
The trial also achieved its primary goal of lowering participants’ A1C level – a measurement of the average amount of glucose in blood over the previous three months – more than a placebo. Participants saw an average reduction of 1.3% to 1.6% from a baseline of 8%.
Glucose, or blood sugar, is the body’s main source of energy. People who have diabetes can’t make enough insulin, a hormone the pancreas makes to help the body keep blood sugar levels in a certain range. People with type 2 diabetes may also have cells that are resistant to the effects of insulin.
GLP-1 drugs help control blood sugar by stimulating the pancreas to release insulin and suppressing the release of another hormone. GLP-1s also help reduce the feeling of hunger and can make people feel full for longer.
Orforglipron helped more than 65% of trial participants get to or maintain their A1C at or under 6.5%, the level at which people are considered to have diabetes, Lilly said.
Dr. Dan Skovronsky, Lilly’s chief scientific officer, said Wednesday that even before the trial results were released within the company, he knew they would be good.
“When I walked into the room to see the results, I saw everybody smiling, so I knew they were about to share good news with me,” he said.
Liver injury like what was seen in the trial of the Pfizer drug is always possible with small-molecule drugs like this one, Skovronsky said, and it is difficult to detect whether it will cause a problem until the drug is tested in enough people.
“We did not see a liver safety signal with ours, which was a relief,” Skovronsky said.
Side effects with the pill were similar to those reported with injectable forms of GLP-1 drugs. The adverse events were considered generally mild to moderate, according to the company, with upset stomach the most commonly reported.
Many people who use injectable GLP-1s eventually quit because of side effects. But by the end of this trial, Skovronsky said, more than 90% of the participants had stuck with the medication.
GLP-1 injections are highly effective, but for many people, they are cost-prohibitive. The injections are also complicated and costly to make.
A daily pill would be easier to use and, because it would be cheaper to manufacture, could possibly lower patient costs, expert say. It’s too early to know how much orforglipron might cost if it’s approved.
Injection drugs have other downsides, as well. They need to be refrigerated and require plastic applications, whereas pills have less packaging.
“Drugs in tablet form are valuable for a lot of patients for a lot of reasons, particularly those who are needle-phobic,” said Dr. Amy Rothberg, a clinical professor of medicine in the Division of Metabolism, Endocrinology & Diabetes in the Department of Internal Medicine and a research professor of nutritional sciences in the School of Public Health at the University of Michigan. “And it probably just simplifies things to just add on another pill, as opposed to taking a shot, which is a little more complex.”
Accessibility to drugs that need to be taken over a long period of time is key, said Dr. Priya Jaisinghani, an endocrinologist who works in obesity medicine at NYU Langone Health.
“As clinicians, our priority is to align treatment with our patients’ preferences to support long-term adherence,” said Jalisinghani, who is also a clinical assistant professor in the Department of Medicine at NYU Grossman School of Medicine and who was not involved with the new research. “For patients who may find injectable therapies challenging or undesirable, an oral alternative may improve both initiation and continuation of therapy.”
Rothberg, who was likewise not involved with the new trial, hopes Lilly will pass on cost savings to patients if the drug is approved.
“We could reach many more people then,” she said.
A growing number of people do need treatment for diabetes or obesity. More than 40% of US adults live with obesity, and about 11.6% of the population – an estimated 38.4 million Americans – had been diagnosed with diabetes as of 2021, according to the US Centers for Disease Control and Prevention. Most have type 2 diabetes.
Skovronsky said that Lilly has already been producing orforglipron pills after getting earlier promising results assuming that the rest of the trials will go well. “That way, we’ll have adequate supply to meet demand,” he said.
Lilly plans to publish the results of its late-stage trial in a peer-reviewed journal and expects to share more results later this year, along with findings from another clinical trial program that it created to evaluate the drug for its weight management qualities. It’s also testing to see if a pill might improve people’s high blood pressure and sleep apnea, two conditions that have been helped with certain injectable GLP-1s.
Lilly said it expects to apply for approval of orforglipron for weight management by the end of the year and submit results concerning its treatment of type 2 diabetes in 2026.