May 14, 2025, 12:25 pm | Read time: 6 minutes
Whether it’s drawing blood or administering medication, needles scare many people, and not everyone can imagine doing it themselves. However, when it comes to severe obesity and Type 2 diabetes, GLP-1 receptor agonists—such as Ozempic and Wegovy—are effective aids. The catch: the medication must be regularly injected with a needle. But a new “weight loss pill” could soon replace this method.
Is the pill for obesity coming? Pharmaceutical company Eli Lilly has released initial Phase 3 results for Orforglipron—the world’s first oral GLP-1 pill that significantly lowers blood sugar and reduces weight. Phase 3 studies are the final stage before potential approval, testing a drug’s efficacy and safety. Orforglipron’s effects are comparable to existing GLP-1 treatments that require injections.
Overview
The Global Problem with Obesity
According to the World Health Organization (WHO), one in eight people worldwide suffered from obesity in 2022. This form of overweight is defined by a body mass index of 30 or higher. Among adults, obesity cases have more than doubled globally since 1990, and among adolescents, they have quadrupled.1 Consequently, the risk of diseases such as type 2 diabetes, cardiovascular diseases, cancer, and others increases. As future projections—cautiously stated—do not look promising, immediate measures to address this health crisis are necessary, according to the medical journal The Lancet.2
What’s in the Pill for Obesity?
Chugai Pharmaceutical developed Orforglipron in 2018, later licensed by Eli Lilly. The active ingredient belongs to the group of GLP-1 receptor agonists—medications that mimic the body’s hormone GLP-1 to regulate blood sugar levels, reduce hunger, and delay gastric emptying. Unlike known injectable substances like semaglutide, found in Ozempic, Orforglipron is based on a small molecule rather than a peptide. This is the crucial difference: It is not immediately broken down in the digestive tract and can therefore be taken as a pill. One pill per day is required, with no dietary restrictions. The simple form of administration could present a lower barrier for many affected individuals compared to regular injections.
How the Medication Was Tested
The pharmaceutical company tested Orforglipron in the Phase 3 study ACHIEVE-1. This clinical trial involved 559 overweight adults with type 2 diabetes whose blood sugar levels were not within the desired range despite diet and exercise. The HbA1c value, which provides information about blood sugar over the past two to three months, served as a marker. In healthy individuals, this value is about 5.7 percent. For type 2 diabetics, values between 6.5 and 7.5 percent are targeted in therapy.3 However, at the start of the study, participants had an average HbA1c value of 8.0 percent and weighed around 90 kilograms. They were randomly assigned to one of four groups: three different dosages of Orforglipron (3, 12, and 36 milligrams) or a placebo.
The treatment lasted 40 weeks. All participants started with a low initial dose and gradually increased to the target amount. The goal was to evaluate the blood sugar-lowering effect of the medication compared to placebo. No other diabetes medications were taken during this time.
Blood Sugar Levels Dropped Significantly
Indeed, Orforglipron showed a significant reduction in HbA1c values across all dosages. The average decrease ranged from 1.3 to 1.6 percentage points, an effect comparable to injectable GLP-1 agents like semaglutide. Over 65 percent of participants receiving the highest dose achieved an HbA1c value of 6.5 percent or lower—below the diabetes threshold.
How Much Weight Did Participants Lose?
The question now on everyone’s mind: Does the pill work as well against obesity as the injections? The study showed that participants lost an average of 7.3 kilograms, about eight percent of their initial weight. However, tirzepatide demonstrated a higher weight loss of 16 to 21 percent in approval studies.4 Ozempic also achieved a notable 15 percent after just over a year of use.5 Eli Lilly’s press release notes that the weight loss of their participants is not yet complete, meaning the plateau has not been reached. The potential effect could exceed eight percent—but that remains to be seen.6
Side Effects Similar to Known Treatments
Despite oral administration, Orforglipron’s side effects are similar to those of known GLP-1 therapies. Gastrointestinal issues were most common, including nausea, vomiting, diarrhea, and constipation. These side effects were mostly mild to moderate and led to therapy discontinuation in only a few cases. Discontinuation rates due to adverse events ranged from four to eight percent—compared to one percent in the placebo group.
Expert Evaluates the Study Results
Cardiologist Professor Naveed Sattar from the University of Glasgow sees great potential in the study results. “These are important findings. New oral agents that lower blood sugar and significantly reduce weight beyond the levels of most existing diabetes therapies are crucial for the future treatment of type 2 diabetes. Current research has shown that obesity not only leads to type 2 diabetes in many people but also significantly contributes to many associated complications. Targeted weight loss often also improves patients’ quality of life,” he commented.7
However, Sattar also emphasizes that not all questions have been answered: “One caveat is that we do not yet know the effects of this newer therapy on cardiovascular events, but future studies will show this. It is also encouraging to learn about the safety profile of these new oral GLP-1RA medications—especially regarding liver values—and we look forward to seeing the data in a full publication in due course.”
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When Will Orforglipron Be Available?
The results of the ACHIEVE-1 study will be presented at this year’s American Diabetes Association annual meeting in June and are set to be published in a scientific journal. Lilly also plans to release more data from the clinical Phase 3 study series “ACHIEVE” soon. Additionally, new results from the parallel study “ATTAIN,” which specifically investigates Orforglipron for weight control, will be available soon.
Eli Lilly plans to apply for approval for the treatment of obesity with the U.S. Food and Drug Administration (FDA) later this year, followed by an application for diabetes treatment in early 2026. The company emphasizes that no supply shortages are expected upon approval.