Space Kitty Archive
Research dossier · version 1 · updated Oct 29, 2026

GLP-1 & Incretin Therapies: State of the Field (October 2026)

Covers semaglutide, tirzepatide, the new oral GLP-1 agonists and next-generation triple-agonist and amylin-combination drugs, with their effects on weight, diabetes, cardiovascular, kidney, heart-failure, liver, sleep-apnea, joint and brain outcomes as of October 2026. The central takeaway: the field has moved from proving weight loss to proving organ protection. Placebo-adjusted mean weight loss at the top doses of pivotal trials in adults without diabetes now ranges from about 9 percentage points (oral orforglipron) to about 21 (retatrutide, not yet approved), and the main open questions are durability after stopping, lean-mass and rare safety signals, cost and access, and how much of the benefit is independent of weight loss.

5,487 words100 sources36 evidence-mapped claims12 benchmarks18 timeline events✓ citation-verified Oct 29, 2026

AI-assisted synthesis of the cited literature, independently fact-checked against its sources; not peer reviewed. Research summary, not medical advice.

Contents

  1. Executive summary
  2. Background and core concepts
  3. Timeline of key milestones
  4. State of the art
  5. Semaglutide: injectable and oral
  6. Tirzepatide and head-to-head evidence
  7. Next-generation agents: triple agonists, amylin combinations, monthly dosing
  8. Oral small molecules
  9. Cardiovascular, kidney and heart-failure outcomes
  10. Liver: MASLD and MASH
  11. Other indications: sleep apnea, osteoarthritis, type 1 diabetes
  12. Neuropsychiatric and addiction outcomes
  13. Real-world effectiveness, persistence and cost
  14. Quantitative benchmarks
  15. Open problems and active debates
  16. Major programs and players
  17. Outlook: what to watch (November 2026 - April 2028)
  18. Key papers
  19. Glossary

Sample findings

  • Once-weekly semaglutide 2.4 mg produced a mean body-weight change of -14.9% vs -2.4% with placebo at 68 weeks in adults with overweight or obesity without diabetes (STEP 1, n=1,961).
  • Tirzepatide 5, 10 and 15 mg produced mean weight changes of -15.0%, -19.5% and -20.9% vs -3.1% with placebo at 72 weeks (SURMOUNT-1, treatment-regimen estimand).
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