Lilly's Oral GLP-1 Drug Achieves Mild Weight Loss vs. Injectables

A New Oral GLP-1 Drug Shows Promising Weight Loss Results

A new oral medication called orforglipron, developed by Eli Lilly, has shown early promise in helping people with obesity lose about 12% of their body weight. This drug, which is taken as a pill once daily, could offer a more convenient alternative to injectable GLP-1 medications that are currently on the market.

According to preliminary data from the first phase 3 clinical trial, orforglipron demonstrated an average weight loss of 12.4% at the highest dose of 36 milligrams. This result was achieved over a 72-week period among more than 3,000 adults who had either obesity or overweight with related medical conditions. The placebo group, however, saw less than 1% weight reduction during the same time frame.

Despite these results, some experts believe the weight loss outcomes are modest compared to other GLP-1 drugs like Wegovy and Zepbound, which can lead to 15% to 25% weight loss. Dr. Wajahat Mehal, a professor of medicine at Yale School of Medicine, noted that orforglipron’s results seem “pretty anemic” when compared to these alternatives. He questioned why anyone would choose this drug over more effective options.

How Orforglipron Works

Orforglipron works by activating the GLP-1 hormone in the gut, which helps regulate hunger, appetite, and insulin secretion. If approved, it would be the first oral GLP-1 medication that doesn’t require restrictions on eating or drinking before taking it. Currently, the only available oral GLP-1 drug is Rybelsus, which must be taken on an empty stomach and requires waiting 30 minutes before eating or drinking again.

The drug also showed benefits beyond weight loss, including reductions in cardiovascular risk markers such as non-HDL cholesterol, triglycerides, and systolic blood pressure across all doses. However, Eli Lilly has only shared top-line results so far, and full details will be presented at a conference next month.

Weight Loss Outcomes in People With Diabetes

In April, Eli Lilly shared additional data showing that people with diabetes lost an average of 8% of their body weight after 40 weeks on the highest dose of orforglipron. It’s important to note that individuals with diabetes typically lose less weight on GLP-1 drugs compared to those without diabetes. Participants in the Attain-1 trial also received diet and exercise counseling and took the drug for nearly a year and a half.

Kenneth Custer, executive vice president and president of Lilly Cardiometabolic Health, had previously stated that the company expected weight loss results similar to the best injectable GLP-1 drugs for patients without diabetes.

Safety Profile and Side Effects

The safety profile of orforglipron appears to be comparable to injectable GLP-1 drugs like Zepbound and Mounjaro. Most side effects were gastrointestinal and mild, often occurring when starting the medication or increasing the dose. Approximately 25% of participants experienced vomiting during the trial, though the frequency of this side effect was not clearly specified.

Dr. Mehal pointed out that even occasional vomiting could deter people from continuing the medication. While many individuals may tolerate nausea, no one tolerates vomiting well.

Potential Benefits of an Oral Option

Oral GLP-1 medications could be particularly beneficial for people who prefer not to use needles. Custer emphasized that around 75% of patients would prefer an oral option if available. However, Dr. Mehal believes the combination of modest weight loss and potential side effects makes orforglipron less appealing as a standalone treatment.

That said, some patients already using injectable GLP-1 drugs might consider adding orforglipron to enhance their results. An oral option could also help individuals maintain weight loss after achieving significant results with injectable medications, especially if orforglipron is more affordable and accessible.

Eli Lilly is currently testing this possibility in the Surmount-5 study, where participants on tirzepatide or semaglutide were re-randomized to switch to orforglipron or a placebo. The results of this study could provide further insight into how effectively the drug works as a weight maintenance therapy.

Future Prospects and Availability

Eli Lilly has not yet announced pricing for orforglipron if it receives FDA approval. However, Custer mentioned that the drug could be produced more cheaply and easily than injectable versions. Its ease of storage and transportation could also make it more globally accessible than current options.

As research continues, orforglipron represents a potential advancement in the treatment of obesity, offering a new option for patients seeking convenience and accessibility.