Weight loss pill instead of injection: How well does Orforglipron work?

New weight-loss injections like "Wegovy" or "Mounjaro" can help with weight loss. But they must be injected subcutaneously once a week, which is uncomfortable for many people. Now, the pharmaceutical company Eli Lilly and Company is planning to launch "Orforglipron," a weight-loss pill with the same mechanism of action.

Orforglipron tablets, like the most effective weight-loss injections, contain a so-called GLP-1 agonist as their active ingredient. This means they mimic the action of the hormone GLP-1. They delay gastric emptying, promote the release of the hormone insulin, and are said to reduce appetite. All of this can lead to significant weight loss.

Initial study results show that orforglipron may be somewhat less effective than injections – although not significantly. Eli Lilly tested the pill in a study with 3,127 overweight and obese participants. Some of them took orforglipron in various doses three times a day, while another group received an inactive placebo, while all participants were required to maintain a healthy diet and exercise.

On average, the group taking the highest dose of the drug lost 12.4 percent of their body weight, equivalent to approximately 12.4 kilograms, over one and a half years. In the placebo group, the weight loss was 0.9 percent (approximately one kilogram), resulting in an average treatment reduction of 11.3 kilograms. The lowest dose resulted in an average weight loss of 7.8 percent of body weight (approximately 8 kilograms).

In previous studies with semaglutide, the active ingredient in Wegovy injections, weight loss was 14.9 percent compared to 2.4 percent with placebo, which would correspond to a treatment-induced reduction of 12.5 percent. Elli Lilly's weight-loss injection, tirzepatide (Mounjaro), which mimics another hormone in addition to GLP-1, was able to reduce weight by an average of 16 percent in studies. This compares to a 2.4 percent reduction with placebo (resulting in 13.4 percent efficacy).

The amount of weight loss achieved with treatment lasting more than one and a half years has not been tested. It is already known from other GLP-1 agonists that after rapid initial weight loss, a plateau is quickly reached, and those affected continue to lose only slightly. Furthermore, there is a risk of rapid rebound after discontinuing the medication. This can actually only be prevented by taking the medication long-term—which must be weighed against the significant health risks associated with it.

A complete list of all adverse effects of orforglipron has not yet been published. The company states in a press release that the side effects are consistent with those expected for GPT-1 agonists. It lists the most frequently observed symptoms: nausea and vomiting, as well as digestive problems such as constipation and diarrhea. Ten percent of participants who received the highest dosage of the weight-loss pill discontinued the study as a result.

However, GPT-1 agonists can have other side effects , as is known from older studies. Semaglutide, for example, is warned about, among other things, inflammation of the pancreas or gallbladder and gallstones, serious allergic reactions, kidney failure, rapid heartbeat, hypoglycemia, and visual disturbances in people with type 2 diabetes, depression and even suicidal thoughts, and thyroid cancer. In animal studies, semaglutide has also caused pancreatic cancer.

Semaglutide will also soon be available in tablet form. The manufacturer of the Wegovy injections, Novo Nordisk, applied to the U.S. Food and Drug Administration (FDA) in May for approval of a pill containing the same active ingredient.

Eli Lilly is now in a race of sorts with its competitor. The company plans to present further study results on orforglipron in September at the annual meeting of the European Association for the Study of Diabetes (EASD) and has announced that it intends to apply for approval by the end of the year.

It is currently unclear whether and when one of the weight-loss pills will come to the German market, and under what conditions. Weight-loss injections containing GPT-1 agonists are currently only approved for the adjunctive treatment of obesity with a BMI of 30 or higher, or with a BMI of 27 or higher if a comorbidity is present. The treatment is not reimbursed by statutory health insurance.