The Pill That Could Change Weight Loss: Why Doctors Are Excited About Orforglipron

Orforglipron, a new once-daily oral medication, could expand obesity treatment options by offering an easier-to-take alternative to injectable weight loss drugs. The U.S. Food and Drug Administration (FDA) accepted the drug application in late 2025 and is reviewing it under an accelerated program designed for significant public health priorities, with a decision expected by April 10, 2026.

How Is Orforglipron Different From Current Weight Loss Drugs?

If you've heard about weight loss medications like semaglutide (Ozempic, Wegovy) or tirzepatide (Zepbound), you know most require weekly injections. Orforglipron takes a different approach. It's a small-molecule, non-peptide glucagon-like peptide-1 (GLP-1) receptor agonist—meaning it activates the same appetite-suppressing pathway as injectable drugs, but in pill form.

The key advantage? Unlike oral semaglutide, the only current oral GLP-1 option, orforglipron doesn't require strict fasting or water-only dosing conditions to work. You simply take it once daily without special preparation, which could make it easier for people to stick with long-term.

What Do the Clinical Trial Results Show?

Orforglipron's application is backed by three major clinical trials involving thousands of participants. Here's what the data revealed:

• Weight Loss in People Without Diabetes: In the ATTAIN-1 trial with over 3,100 participants, the highest dose (36 mg) led to an average 11.2% body weight reduction after 72 weeks, compared to just 2.1% with placebo. More than half (54.6%) of people taking the 36 mg dose lost at least 10% of their body weight.
• Weight Loss in People With Type 2 Diabetes: The ATTAIN-2 trial included over 1,600 participants with both obesity and diabetes. The 36 mg dose produced a 9.6% average weight reduction, with 45.6% of participants achieving at least 10% weight loss. Bonus: blood sugar control improved significantly, with hemoglobin A1C (a measure of long-term blood sugar) dropping by up to 1.66%.
• Maintaining Weight Loss After Switching: The ATTAIN-MAINTAIN trial tested whether people could maintain their weight loss after switching from injectable drugs. Participants who had previously lost weight on semaglutide or tirzepatide and then switched to oral orforglipron kept nearly all their results—regaining only about 2 pounds after semaglutide or 11 pounds after tirzepatide over one year.

Side effects were generally mild to moderate, with gastrointestinal issues (nausea, constipation, diarrhea) being the most common, especially during the initial dose-escalation phase.

Why Does This Matter for Weight Management?

The obesity treatment landscape has shifted dramatically in recent years with the rise of GLP-1 drugs. However, many people struggle with weekly injections—whether due to needle anxiety, inconvenience, or simply forgetting doses. An effective once-daily pill without strict dosing requirements could remove a major barrier to treatment adherence.

The ATTAIN-MAINTAIN results are particularly noteworthy because they suggest orforglipron could serve as a maintenance option for people who've already achieved weight loss on injectable therapies. This flexibility could help more people sustain their results long-term.

What's Next for Orforglipron?

Beyond weight management, Eli Lilly plans to submit an additional application this year for orforglipron as a type 2 diabetes treatment, based on the Phase 3 ACHIEVE clinical trial program evaluating its effects on blood sugar control and heart health outcomes.

The FDA's accelerated review under the Commissioner's National Priority Voucher Pilot Program reflects the agency's recognition that obesity is a significant public health priority. This intensive, senior-level review maintains the FDA's usual safety and efficacy standards while shortening the timeline compared to traditional reviews.

If approved, orforglipron could join a growing arsenal of oral GLP-1 options, offering patients more choices based on their preferences, medical history, and lifestyle. For now, the weight loss community is watching closely for the FDA's April decision.