Research · GLP-1 · Reviewed by Thomas Okafor, Peptide Chemist · Published October 6, 2026

Most GLP-1 drugs are peptides: chains of amino acids modeled on the gut hormone GLP-1. 2026 brought news on two fronts that show where the class is heading. One is a peptide that acts on three hormone receptors at once. The other is a GLP-1 drug that isn’t a peptide at all.

Retatrutide: one peptide, three receptors

Semaglutide acts on the GLP-1 receptor. Tirzepatide acts on GLP-1 and GIP receptors. Retatrutide, from Eli Lilly, adds a third: the glucagon receptor. All three trials below ran for 80 weeks and compared weekly injections against placebo.

Trial (announced) Who took part Average weight change at 80 weeks
TRIUMPH-1 (May 21, 2026) 2,339 adults with obesity, or overweight with a weight-related condition, without diabetes 4 mg: −19.0% · 9 mg: −25.9% · 12 mg: −28.3% [1][2]
TRIUMPH-2 (July 23, 2026) 1,152 adults with type 2 diabetes and obesity or overweight 4 mg: −12.7% · 9 mg: −19.1% · 12 mg: −20.8% · placebo: −4.0% [3]
TRIUMPH-3 (July 23, 2026) 1,949 adults with a BMI of 35 or higher and established cardiovascular disease 9 mg: −21.6% · 12 mg: −22.6% · placebo: −3.2% [3]

In a pre-planned extension of TRIUMPH-1 for participants with a BMI of 35 or higher, the 12 mg group reached an average of 30.3% at 104 weeks [2]. In TRIUMPH-2, A1C fell by up to 1.6 percentage points from a baseline of 7.7%, compared with 0.2 points on placebo [3].

Side effects and dropouts

The most common side effects were gastrointestinal. In TRIUMPH-1, at the 12 mg dose versus placebo, nausea was reported by 42.4% vs 14.8% of participants, diarrhea by 32.0% vs 13.5%, constipation by 26.1% vs 10.9% and vomiting by 25.3% vs 4.8% [2]. Discontinuation due to adverse events was 11.3% at 12 mg, compared with 4.9% on placebo [2]. Across TRIUMPH-2 and TRIUMPH-3, discontinuation ranged from 3.8% to 11.6% on retatrutide versus 4.9% on placebo [3].

Where it goes from here

Lilly has said it plans to file for US approval in the first quarter of 2027 [3]. Until FDA reviews and approves it, retatrutide is not an approved drug and is not available by prescription. Products sold online as “retatrutide” are not the approved medicine, because no approved version exists yet.

Orforglipron: a GLP-1 pill that isn’t a peptide

On April 1, 2026, FDA approved orforglipron, sold as Foundayo, for chronic weight management in adults with obesity, or overweight with at least one weight-related condition [4][5]. It was reviewed under the Commissioner’s National Priority Voucher pilot program, and approval came about 50 days after filing [4].

What sets it apart for a peptide site is its chemistry. Orforglipron is a small molecule that activates the GLP-1 receptor without being built from amino acids [4]. Peptides are usually broken down by digestion, which is why most GLP-1 drugs are injected and why the existing oral semaglutide tablet needs an absorption enhancer and strict dosing conditions [4]. A small molecule avoids that problem, and orforglipron can be taken without food or water restrictions [4].

In the trial data cited at approval, adults with overweight or obesity lost an average of 7.8%, 9.3% and 12.4% of body weight at 72 weeks on the 6 mg, 12 mg and 36 mg doses [4].

WADA’s 2027 Prohibited List keeps GLP-1 receptor agonists permitted for athletes. See our WADA 2027 update in this section for details.

For more on how these compounds are studied, browse Weight & Metabolism.

Semaglutide, tirzepatide and orforglipron are prescription medicines; retatrutide is investigational. This article reports published trial results for education only. Questions about treatment belong with a licensed clinician.

Sources

  1. Eli Lilly, “Lilly’s triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial,” May 21, 2026. https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss
  2. AJMC, “Retatrutide Achieves Up to 30.3% Average Weight Loss in Phase 3 TRIUMPH-1 Trial” (ClinicalTrials.gov NCT05929066). https://www.ajmc.com/view/retatrutide-achieves-up-to-30-3-average-weight-loss-in-phase-3-triumph-1-trial
  3. Pharmaceutical Executive, “Retatrutide Delivers Up to 22.6% Weight Loss in Two New Phase III Trials,” July 2026. https://www.pharmexec.com/view/retatrutide-delivers-22-weight-loss-two-phase-iii-trials
  4. Healio, “FDA approves orforglipron, an oral GLP-1 for adults with obesity,” April 1, 2026. https://www.healio.com/news/endocrinology/20260401/fda-approves-orforglipron-an-oral-glp1-for-adults-with-obesity
  5. ABC7 News (AP), “FDA grants speedy approval to Eli Lilly’s weight-loss pill for obesity.” https://abc7news.com/post/fda-grants-speedy-approval-eli-lillys-weight-loss-glp-1-pill-foundayo-obesity/18823509/