At this point we are no strangers to GLP-1 medications to treat diabetes and obesity. They have permeated our health consciousness with over 41 million Americans having tried the medications and roughly 1 in 8 Americans on an injectable GLP-1 medication today. The use of these therapies for obesity are reported to result in mean weight reductions of 15 to 20% and demonstrated additional health benefits including managing metabolic dysfunction and decreasing cardiovascular disease risk.
While the use of these injectable medications continues to rise, limitations exist. Many patients don’t like injecting themselves weekly and they continue to struggle to afford the high cost of the medications. An oral GLP-1 receptor agonist may alleviate these concerns and improve access for patients. The ATTAIN-1 trial recently evaluated an new oral GLP-1 receptor agonist medication, Orforglipron, developed by Eli Lilly Pharmaceuticals, to evaluate whether the medication helps people with obesity lose weight safely.
The randomized control clinical trial included over 3,100 adults in nine countries who were diagnosed with obesity but not diabetes. Everyone in the study was asked to follow a healthy diet and regular physical activity in addition to taking a daily pill that was either the medication or a placebo (“dummy”) pill. Participants were randomly assigned and blinded so they did not know which group they were assigned to. Participants receiving the intervention were assigned one of three doses: 6 mg, 12 mg, or 36 mg and took the pill once a day for 72 weeks. The end goal was to measure how much their body weight changed over the study period but they also tracked other measures like blood pressure, cholesterol, and waist circumference.
The Findings
People taking Orforglipron lost more weight overall than those taking the placebo. On the 6mg dose patients had 7.5% weight loss, 8.4% weight loss for the 12mg dose and 11.2% weight loss for the 36 mg dose. The placebo group only achieved 2.1% weight loss. Among the participants on the highest dose (36 mg) more than half (55%) lost at least 10% of their weight. Close to 20% of patients on that high dose lost 20% or more.
Some Considerations
The most common side effects were digestive issues like nausea, constipation, diarrhea and most participants rated it as mild or moderate. A small portion of participants (5%) taking the Orforglipron treatment stopped due to side effects. Like any clinical trial, they evaluated the safety of the medication. Three patients experienced mild pancreatitis (inflammation of the pancreas) in the Orforglipron group, but no complications were reported in those cases.
This is not the first oral GLP-1 medication on the market. Oral semaglutide, Rybelsus, achieved an average weight loss of 15.1% in a trial of 68 weeks with approximately 700 patients. However, this formulation is currently FDA-approved for Type 2 Diabetes only. A larger meta-analysis showed that among oral formulations for GLP-1s receptor agonists, Orforglipron did have the highest risk of nausea.
What Does This Mean For Patients
Orforglipron, if approved by the FDA for treatment of obesity, may offer a convenient oral pill option for patients who don’t want to use an injectable medication. We don’t know how well the medication will be covered by health insurance or what the projected out-of-pocket costs will be.
The weight loss seen in the clinical trial, especially at the highest dose, is clinically meaningful. The researchers saw other beneficial secondary outcomes including lowered blood pressure, decreased cholesterol, and improved metabolic health. Is the oral GLP-1 comparable to the injectable GLP-1s? A head-to-head comparison trial has not been done yet so we can’t say for sure.
This trial also did not study whether this medication should be used for the treatment of type 2 diabetes so more research is needed.
The Bottom Line
This study demonstrates that Orforglipron, a daily pill, has helped many adults with obesity lose a significant amount of weight over about a year and a half. Side effects, especially GI upset, were common, but overall mild. This medication could become yet another helpful tool for medical weight loss in patients who prefer pills.
If you or a loved one is interested in exploring medical weight loss, please connect with us to learn more. Both Dr. Mintz and Dr. Taskier practice medical weight loss in addition to lifestyle medicine. Schedule a meet and greet with us today.
References:
Ismaiel, A., Scarlata, G. G. M., Boitos, I., Leucuta, D.-C., Popa, S.-L., Al Srouji, N., Abenavoli, L., & Dumitrascu, D. L. (2025). Gastrointestinal adverse events associated with GLP-1 RA in non-diabetic patients with overweight or obesity: A systematic review and network meta-analysis. International Journal of Obesity (London), 49(10), 1946–1957. https://doi.org/10.1038/s41366-025-01859-6 PubMed
Elmaleh-Sachs, A., Schwartz, J. L., Bramante, C. T., Nicklas, J. M., Gudzune, K. A., & Jay, M. (2023). Obesity management in adults: A review. JAMA, 330(20), 2000–2015. https://doi.org/10.1001/jama.2023.19897 PubMed+1
(2025). Efficacy and safety of orforglipron in adults with obesity without diabetes. New England Journal of Medicine. Advance online publication. https://doi.org/10.1056/NEJMoa2511774
Drucker, D. J. (2025). GLP-1–based therapies for diabetes, obesity, and beyond. Nature Reviews Drug Discovery, 24(7), 570. https://doi.org/10.1038/s41573-025-01231-3 PubMed
(2024). The public’s use and views of GLP-1 drugs. KFF Health Tracking Poll, May 2024. Kaiser Family Foundation. https://www.kff.org/health-costs/kff-health-tracking-poll-may-2024-the-publics-use-and-views-of-glp-1-drugs/ KFF