Oral Weight Loss Pill Orforglipron Helps Maintain Results After Injectable GLP-1 Drugs

Two new randomized studies published in Nature Medicine demonstrate that daily oral orforglipron helps patients maintain most of the weight loss achieved with injectable GLP-1 drugs such as tirzepatide and semaglutide. The double-blind, placebo-controlled trial enrolled 376 adults across 29 sites in the United States who had completed 72 weeks of treatment in the SURMOUNT-5 study.

Participants were randomized to receive orforglipron at a maximum tolerated dose of 36 mg or placebo once daily for 52 weeks. Among those who had reached a weight plateau on tirzepatide, orforglipron users maintained 74.7 percent of their prior weight reduction after one year compared with 49.2 percent for the placebo group.

The estimated treatment difference was 25.5 percentage points. Patients previously treated with semaglutide who switched to orforglipron retained 79.3 percent of their weight loss versus 37.6 percent on placebo, producing an estimated treatment difference of 41.7 percentage points.

Both primary endpoints reached statistical significance with P values below 0.001. All key secondary endpoints were also met. More than half of semaglutide patients on orforglipron maintained at least 80 percent of their prior weight loss, compared with fewer than 7 percent on placebo.

Participants who continued orforglipron also preserved improvements in waist circumference, blood pressure, lipids, fasting glucose and HbA1c levels achieved during the injectable phase. At the end of the maintenance year, mean body weight stood at approximately 96 kg for the tirzepatide-to-orforglipron cohort.