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Retatrutide Guide

Reference asset · April 2026

GLP-1 timeline: from exenatide (2005) to retatrutide (2026?)

A two-decade chronology of the most consequential drug class in modern medicine. Every approval, pivotal trial, and regulatory inflection point that brought the GLP-1 era to its current shape.

Editorially reviewed April 2026Updated April 28, 2026Independent medical reviewer onboarding

Timeline · 2005 – present

Two decades of GLP-1: every milestone, in order

  1. Approval· Exenatide

    Exenatide approved (Byetta) — first GLP-1 agonist

    FDA approves Byetta for type 2 diabetes. Twice-daily injection. Marks the start of the GLP-1 era.

  2. Approval· Liraglutide

    Liraglutide approved (Victoza) for type 2 diabetes

    Once-daily GLP-1 with longer half-life. Establishes the daily-injection format and sets the stage for chronic dosing in metabolic disease.

  3. Approval· Exenatide ER

    Bydureon approved — first once-weekly GLP-1

    Once-weekly extended-release exenatide. The first proof that once-weekly cadence is viable for the class.

  4. Approval· Liraglutide

    Saxenda approved — first GLP-1 for chronic weight management

    Higher-dose liraglutide receives obesity indication. SCALE Obesity trial showed ~8% mean weight loss vs. placebo at 56 weeks.

  5. Approval· Semaglutide

    Ozempic approved for type 2 diabetes

    Novo Nordisk's once-weekly semaglutide enters the T2D market. Larger HbA1c reductions than predecessors and meaningful weight loss as a side benefit.

  6. Approval· Semaglutide

    Rybelsus approved — first oral GLP-1

    Daily oral semaglutide for T2D. Demonstrates that GLP-1 peptides can be administered orally with sufficient bioavailability.

  7. Publication· Semaglutide

    STEP 1 published — semaglutide produces ~15% weight loss in obesity

    STEP 1 Phase 3 trial in NEJM: ~14.9% mean weight loss at 68 weeks. The headline result that re-frames obesity as a treatable medical condition for many clinicians.

  8. Approval· Semaglutide

    Wegovy approved for chronic weight management

    Higher-dose semaglutide receives obesity indication. Demand quickly outstrips supply; shortages persist for years.

  9. Approval· Tirzepatide

    Mounjaro approved for type 2 diabetes

    Eli Lilly's GLP-1/GIP dual agonist enters the T2D market. First multi-receptor agonist to win approval.

  10. Discovery· Coskun et al.

    Retatrutide discovery paper published

    Coskun et al. publish the LY3437943 (retatrutide) discovery paper in Cell Metabolism, establishing the triple-agonist mechanism and Phase 1 proof of concept.

  11. Publication· Retatrutide

    Phase 2 obesity trial published — ~24% weight loss at 48 weeks

    Jastreboff et al. publish retatrutide Phase 2 obesity results in NEJM. The 12 mg dose produces an average 24.2% weight loss at 48 weeks — the largest ever reported in a published obesity-drug trial.

  12. Publication· Retatrutide

    Phase 2 type 2 diabetes results in The Lancet

    Rosenstock et al.: ~2.0 percentage point HbA1c reduction at 36 weeks at the highest dose, with ~17% weight loss as a co-benefit.

  13. Approval· Tirzepatide

    Zepbound approved for chronic weight management

    Tirzepatide receives obesity indication based on SURMOUNT-1 (~21% weight loss at 72 weeks) — the largest weight loss ever approved at the time.

  14. Corporate· LillyDirect

    Lilly launches direct-to-consumer Zepbound vials program

    Self-pay program brings entry-level Zepbound pricing to as low as $349 per month. Shifts the access conversation toward cash-pay channels.

  15. Trial· Survodutide

    Survodutide Phase 2 readout — GLP-1/glucagon dual agonist

    Boehringer / Zealand's GLP-1/glucagon dual agonist reports Phase 2 obesity results, validating the glucagon-receptor approach as an alternative path to multi-receptor weight loss.

  16. Trial· Retatrutide

    All four TRIUMPH Phase 3 trials reach full enrollment

    Lilly confirms TRIUMPH-1 through TRIUMPH-4 are fully enrolled, setting up sequential 2026 readouts.

  17. Trial· Orforglipron

    Orforglipron oral GLP-1 Phase 3 readout

    Lilly's daily oral GLP-1 reports Phase 3 efficacy. Establishes oral as a viable channel for chronic-weight-management market segments.

  18. Trial· Retatrutide

    TRIUMPH-1 topline readout (expected)

    Lilly guidance points to first Phase 3 readouts during 2026. Will be the largest weight-loss dataset for retatrutide to date.

  19. Regulatory· Retatrutide

    Possible US approval decision

    Standard FDA review of a complete submission takes 10-12 months. Late 2026 / 2027 is the most commonly cited analyst window for a potential US approval decision.

Highlighted events mark inflection points for the drug class — first-in-class approvals, headline trial readouts, or major regulatory milestones. Not an exhaustive list of every GLP-1-class event; selected for cross-class significance.

Five eras in one timeline

Looking at the timeline from a distance, five distinct phases of the GLP-1 era come into focus.

1. The diabetes years (2005 – 2014)

Exenatide, liraglutide, and the first wave of GLP-1 drugs were developed and marketed for type 2 diabetes. Weight loss was an observed side benefit, not the primary indication. Cadence moved from twice-daily to daily to once-weekly over this period.

2. The obesity pivot (2014 – 2020)

Saxenda's 2014 approval was the first GLP-1 drug cleared for chronic weight management. The category was small. Liraglutide's ~8% mean weight loss was clinically meaningful but not transformative.

3. The semaglutide breakthrough (2021 – 2022)

STEP 1 (March 2021) and Wegovy's approval (June 2021) changed everything. Once a drug could deliver ~15% weight loss with weekly injections, obesity treatment moved from niche to mainstream. Demand outpaced supply for years.

4. The multi-receptor era (2022 – 2025)

Tirzepatide's Mounjaro/Zepbound launches established that adding receptor targets to a single molecule produced larger weight loss. Retatrutide's 2023 Phase 2 readout (~24% at 48 weeks) suggested the trajectory continues. CagriSema, survodutide, mazdutide, and orforglipron all advanced through this period.

5. The pivotal Phase 3 readouts (2026 – 2027, expected)

The next two years will determine whether retatrutide replicates Phase 2 in larger Phase 3 studies and whether the broader pipeline of next-generation GLP-1 drugs converts trial promise into approved products. The TRIUMPH program is the centerpiece.

What the timeline doesn't show

  • Demand and supply.The Wegovy and Zepbound launches both ran into severe supply constraints. The timeline doesn't capture the patient-access story of the last several years.
  • Compounding. Compounded semaglutide and tirzepatide became a meaningful access channel during shortage windows. Regulatory and legal status has shifted repeatedly and is not detailed here.
  • Cardiovascular outcomes.Major cardiovascular outcomes trials (LEADER, SUSTAIN-6, SELECT) are not on this timeline. They are critical to the class's standing but tangential to the obesity thread.
  • Earlier-stage candidates. Phase 1 and preclinical molecules are not on the timeline. Many will enter Phase 2 in 2026-2027.

Update history

  • April 2026 — Initial publication.

Sources

Primary sources cited on this page

  1. U.S. Food and Drug Administration. Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book). FDA. 2026. Source ↗
  2. Wilding JPH, et al.. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021. Source ↗
  3. Jastreboff AM, et al.. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med. 2022. Source ↗
  4. Jastreboff AM, et al.. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med. 2023. Source ↗
  5. Coskun T, et al.. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss. Cell Metabolism. 2022. Source ↗
  6. Pi-Sunyer X, et al.. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management (SCALE Obesity). N Engl J Med. 2015. Source ↗