For how we live.
An updated Annals review now covers 38 randomised trials and 25,816 people. Tirzepatide leads the marketed drugs at 19.0% placebo-subtracted weight loss; the experimental multiagonists run higher.
Orforglipron removes the injection from weight-loss medicine — a real change for people who refused one. Supply, cost, and coverage are the harder problems it does not solve.
Tirzepatide topped weight loss at 14.9%. But only subcutaneous semaglutide showed a mortality benefit — and no drug moved the needle on quality of life or kidney failure.
Lilly's oral GLP-1 pill actually lowered liver enzymes on average, and its rate of serious liver-injury criteria matched placebo exactly — six cases in each group, none attributable to the drug.
ATTAIN-MAINTAIN tested orforglipron as a maintenance therapy for people who'd already lost weight on tirzepatide or semaglutide. Those on placebo regained roughly half of what the pill preserved.
ACHIEVE-3 randomised 1,698 people to orforglipron or oral semaglutide for 52 weeks. Orforglipron cut HbA1c more at every dose comparison — and produced more side effects and more dropouts.
In ATTAIN-2, the highest dose of the oral GLP-1 pill cut body weight 9.6% over 72 weeks in adults with type 2 diabetes, against 11.2% in the earlier trial of adults without diabetes.