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

Research dossier · v1 · updated 2026-10-29 · 5,487 words · 100 sources · 36 claims · verification: verified

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.

## Contents

- Executive summary
- Background and core concepts
- Timeline of key milestones
- State of the art
  - Semaglutide: injectable and oral
  - Tirzepatide and head-to-head evidence
  - Next-generation agents: triple agonists, amylin combinations, monthly dosing
  - Oral small molecules
  - Cardiovascular, kidney and heart-failure outcomes
  - Liver: MASLD and MASH
  - Other indications: sleep apnea, osteoarthritis, type 1 diabetes
  - Neuropsychiatric and addiction outcomes
  - Real-world effectiveness, persistence and cost
  - Quantitative benchmarks
- Open problems and active debates
- Major programs and players
- Outlook: what to watch (November 2026 - April 2028)
- Key papers
- 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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