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Next Wave of Weight-Loss Drugs Advances With Pills and Multi‑Hormone Shots

Early readouts point to stronger, easier‑to‑take options as approvals and long‑term safety remain unresolved.

Overview

  • Eli Lilly’s oral GLP‑1 pill orforglipron showed greater average weight loss than Novo Nordisk’s oral semaglutide in a year‑long study at top dose and is designed for once‑daily use without food or water restrictions.
  • Pipeline strategies are broadening beyond single‑hormone GLP‑1s, including triple‑agonist retatrutide with roughly 24% average loss in Phase 2 and amylin‑based approaches that aim to reduce gastrointestinal side effects and preserve lean mass.
  • Combination candidates such as Novo Nordisk’s CagriSema reported about 20% weight loss in trials with signals of lower blood pressure and inflammation, and developers are testing more convenient schedules like monthly injections.
  • Despite metabolic gains, expectations for extra‑metabolic benefits were tempered after Novo Nordisk reported that oral semaglutide did not slow Alzheimer’s progression in large trials.
  • New studies highlight unanswered questions, including conflicting findings on pregnancy‑related risks and evidence of weight regain after stopping tirzepatide, reinforcing calls for personalized selection and longer‑term data.