Clinical · 2026-02-10

Five years after STEP-1: the GLP-1 obesity era, in numbers

On the five-year anniversary of STEP-1's NEJM publication, a perspective piece looks at how the field has evolved.

February 2026 marks five years since the publication of STEP-1 (Wilding et al., NEJM 2021;384:989–1002), the trial that established semaglutide 2.4 mg as the first non-surgical obesity therapy capable of producing double-digit percentage weight loss.

A perspective piece this month puts the milestones in numbers: from a single FDA-approved injectable GLP-1 for obesity in 2014 (liraglutide 3.0 mg), to two pivotal phase-3 trials reading out in 2021 (STEP-1 for semaglutide, then SURMOUNT-1 for tirzepatide in 2022), to four FDA-approved indications for the two agents (T2D, chronic weight management, OSA, CV risk reduction) by 2026, plus an entire compounded-telehealth supply chain that did not exist before 2022.

The piece notes that the next generation of triple-agonist therapies (retatrutide, others) is poised to push the effect-size frontier still further over the second half of the decade.

By Dr. ParmisReviewed by Adam Kennah, M.D.Published February 10, 2026Updated May 25, 2026

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