Orforglipron is administered orally, once daily as a pill.

How does orforglipron work?

Orforglipron is a nonpeptide glucagon-like peptide-1 (GLP-1) receptor agonist that works by binding to GLP-1 receptors and stimulating insulin release from the pancreas when it is needed. It also slows down how fast food travels through your digestive tract. This can help you feel fuller for longer, reduce how much you eat, and lead to weight loss.

How effective is orforglipron?

Results of two phase 2 trials funded by Eli Lilly reported favorable results with orforglipron compared to placebo. Frias et al., 2023 also reported a comparison with dulaglutide (Trulicity).

One phase 2 randomized, double-blind trial of 272 participants with an average baseline weight of 108.7kg (average BMI of 37.9 kg/m2) reported (Warton, et al. 2023):

• A weight change of at least 10% occurred in 46% to 75% of people who received orforglipron by week 36 compared to only 9% of those receiving placebo (an inactive tablet)
• The average change from the starting weight was a loss of 9.4% to 14.7% with orforglipron compared to a loss of 2.3% with placebo
• All prespecified improvements in weight and cardiometabolic measures were met by the trial
• The most common side effects were mild to moderate gastrointestinal events and led to discontinuation of orforglipron in 10% to 17% of participants.

A second phase 2 randomized, double-blind trial of 383 participants with an average BMI of 35.2 kg/m2 reported (Frias, et al. 2023):

• Dosages of orforglipron 12mg and greater showed significant reductions in HbA1c and bodyweight compared with placebo or dulaglutide
• At week 26, there was a reduction in HbA1c of up to 2.1% with orforglipron, 0.43% with placebo, and 1.10% with dulaglutide.
• A reduction in body weight after 26 weeks of 10.1kg with orforglipron versus a loss of 2.2kg for placebo and a loss of 3.9kg for dulaglutide was also reported.
• Adverse events were reported in 61.8% to 88.9% of orforglipron treated patients, compared to 61.8% with placebo and 56% with dulaglutide. Most adverse events were mild to moderate gastrointestinal events. Clinically significant hypoglycemia was reported in 3 orforglipron patients and 1 dulaglutide patient. 80 patients did not complete 26 weeks of treatment.

Who makes orforglipron?

Orforglipron is made by Lilly.

Lilly also makes Mounjaro, an injectable dual GIP/GLP-1 receptor agonist which helps lower blood sugar levels in people with type 2 diabetes. Mounjaro is currently in phase 3 clinical trials for weight loss but is not yet FDA approved for weight loss.