Mazdutide

IBI362 / LY3305677 · A-tier (Dr. Alex Tatem) · Strong evidence

The first approved drug that pairs GLP-1 with glucagon activity — think retatrutide without the GIP piece. Strong phase 3 data in China and promising US phase 2 results.

Dr. Tatem’s take

A tier: “a legit compound” with good phase 2 and 3 data. Mechanistically retatrutide “should absolutely smoke it,” so the open question is where it lands among GLP-1s.

In Dr. Tatem’s tier list

• A GLP-1 drug most people haven’t heard of yet, with “really, really good phase 2 and phase 3 data” and approval in China.
• Mechanism map: tirzepatide = GLP-1 + GIP; retatrutide = GLP-1 + GIP + glucagon; mazdutide = GLP-1 + glucagon — “think of it as retatrutide but minus the GIP activation.”
• It will work because semaglutide works, and glucagon activity may help liver health.
• The question is whether glucagon without GIP adds much — retatrutide is coming first and should outperform it. Verdict: A tier.

History & background

Mazdutide was discovered by Eli Lilly, modeled on oxyntomodulin, a natural gut hormone that activates both GLP-1 and glucagon receptors. Lilly licensed China rights to Innovent Biologics in 2018.

Innovent ran the phase 3 GLORY and DREAMS programs, and China’s regulator approved it in June 2025 — the first dual GLP-1/glucagon drug approved anywhere. Lilly’s US phase 2 results were published in August 2026.

Benefits

• 14% average weight loss at 48 weeks on 6 mg (GLORY-1, n=610).
• Up to 18% at 32 weeks on 16 mg in a US phase 2 trial.
• Beat semaglutide 1 mg on weight and blood sugar in a head-to-head diabetes trial (press release).
• Glucagon activity may help liver fat.

Risks

• GI effects are common: nausea in 33–51% in GLORY-1.
• About 1 in 5 quit the highest US phase 2 dose due to side effects.
• Presumed GLP-1 class risks (pancreatitis, gallbladder disease).

Dosing protocols (informational, labeled by evidence)

• Clinical trial / label: Phase 3 GLORY-1 (China) — 4 or 6 mg/wk maintenance, SubQ, Weekly, 48 wk (−12.0% / −14.8% vs −0.5% placebo)
• Clinical trial / label: NMPA (China) approved product — Maintenance 4–6 mg/wk (9 mg studied in GLORY-2), SubQ, Weekly, Chronic

Status: Approved in China (June 2025) for chronic weight management. Investigational in the US (Eli Lilly holds rights outside China).

Grade and commentary: Dr. Alex Tatem. Watch: Truth About More Popular Peptides (What Works, What’s Overhyped) | Peptide Tier List pt.2. Subscribe: @DrAlexTatem.