LY3437943-Maz
Mazdutide (LY3305677, IBI362) is a dual GLP-1 receptor / glucagon receptor (GCGR) co-agonist developed by Eli Lilly and Innovent Biologics, currently in late-stage clinical trials for obesity and type 2 diabetes. Architecturally similar to Semaglutide (lipidated peptide with fatty acid tail for albumin-mediated extended half-life) but adds glucagon receptor agonism for enhanced fat oxidation and energy expenditure on top of GLP-1's appetite suppression and insulin sensitization.
Same day each week. Inject into abdominal subcutaneous tissue, thigh, or upper arm. Rotate sites. Pen device or reconstituted vial. Take with a meal during titration to reduce nausea.
Start here. Every protocol below is ordered lowest-first. Begin at the smallest effective dose, hold about a week to assess tolerance, and step up only if needed.
Mazdutide simultaneously activates two G-protein-coupled receptors with complementary metabolic actions:
Expressed on pancreatic beta cells, hypothalamic appetite centers, and gastrointestinal smooth muscle. Activation drives glucose-dependent insulin secretion, glucagon suppression (counterintuitively coexists with the glucagon receptor agonism elsewhere), delayed gastric emptying, and hypothalamic appetite reduction. Same mechanism as Semaglutide.
Expressed on hepatocytes and adipocytes. Activation increases hepatic fat oxidation, gluconeogenesis (counterbalanced by GLP-1's insulin-mediated suppression), and energy expenditure. The GCGR component is what distinguishes mazdutide from pure GLP-1 agonists - it adds a thermogenic and lipolytic drive.
Appetite suppression (GLP-1) + increased energy expenditure (GCGR) + hepatic fat reduction (GCGR) = larger weight loss than GLP-1 alone in head-to-head comparisons. The GCGR-driven hepatic fat oxidation explains MASH/NAFLD interest.
C-20 fatty acid tail binds serum albumin reversibly, extending plasma half-life to ~5-7 days and enabling weekly dosing - same architecture as Semaglutide and Tirzepatide.
GLP-1 component provides glucose-dependent insulin secretion (low hypoglycemia risk vs sulfonylureas). GCGR component's hepatic glucose output is offset by GLP-1's insulin secretion - net effect is glucose lowering similar to other GLP-1 RAs in type 2 diabetes populations.
Week 1-4: appetite suppression, GI side effects most prominent. Expect 2-4% body weight reduction by week 4.
Month 2-6: peak weight loss velocity. Sustained 8-12% body weight reduction typical at maintenance dose.
Month 6-12+: plateau. -14% peak weight loss at 6mg dose per GLORY-1 36-week data. Long-term beyond Phase 3 not established.
Each reference below was re-fetched from its PubMed record, and the quoted sentence was confirmed to appear in that abstract and to support the claim it sits under. Follow any of them to read the source.
Evidence boundary from the checked abstract: We further explored the safety and efficacy of mazdutide dosed up to 9 mg and 10 mg.
We further explored the safety and efficacy of mazdutide dosed up to 9 mg and 10 mg.
Evidence scope. This entry supports only the exact statement quoted from the live abstract; it does not independently verify OnePin's displayed dose, route, frequency, formulation, population, or broader mechanism.
Claims we could not support
No abstract we checked supports these for this molecule at this route. That is not the same as saying they are false — it marks where the evidence is missing.
Dose/route: 1.5mg; Subcutaneous (SubQ) injection; 1x weekly. No checked live PubMed abstract verified this exact displayed dose, route, and frequency for the same molecule/formulation and relevant population.
Primary safety claim: No primary safety text present in source JSON. No checked live PubMed abstract directly verified this source-JSON safety claim at the displayed formulation, route, and regimen.
Lipidation drives extended half-life
Post-injection (SubQ)
Weekly steady-state achieved after 4-5 weekly doses
subQ ~40-60%
Weekly dosing maintains therapeutic plasma concentration
Hepatic and renal proteolysis; lipidation slows clearance via albumin binding
Storage. Lyophilized vial: refrigerate (2-8°C / 36-46°F). Do NOT freeze. Light-sensitive. After reconstitution with bacteriostatic water: refrigerate, use within 28 days. Pen-device formulations have specific post-loading expiration windows. Discard if cloudy, discolored, or contains particulates. Lipidated peptide is generally robust to brief room-temperature exposure during travel but should not be left unrefrigerated for extended periods.
Approved by China NMPA (National Medical Products Administration) in 2025 for type 2 diabetes and chronic weight management - Innovent Biologics (China license) and Eli Lilly co-developers. NOT FDA-approved or EMA-approved as of this writing - regulatory submissions ongoing. Outside China, mazdutide is investigational. Sale of research-grade mazdutide for human use in non-approved jurisdictions follows the same legal framework as other research-chemical peptides (gray-area; not FDA-endorsed). Class S2 WADA prohibition for peptide hormones applies.
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