OnePin Peptide Library · Weight
Mazdutide
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.
How it works
Mazdutide simultaneously activates two G-protein-coupled receptors with complementary metabolic actions:
GLP-1 Receptor (GLP-1R)
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.
Glucagon Receptor (GCGR)
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.
Net Effect
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.
Lipidation
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.
Glycemic Control
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.
What to expect
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.
Evidence
Interactions & stacking
What's safe to combine, and what belongs in a separate pin.
Keep separate
Side effects & safety
Commonly reported
- Nausea (most common, dose-dependent, often improves with titration)
- Vomiting
- Diarrhea or constipation
- Decreased appetite (intended)
- Injection site reactions
- Headache
- Fatigue (early dose tier)
- Mild gallbladder symptoms in some users
Less common & notes
- Pancreatitis (class warning - personal/family history is contraindication).
- Gallbladder disease, cholelithiasis - rapid weight loss is itself a gallstone risk factor.
- Acute kidney injury secondary to dehydration from severe GI side effects.
- Diabetic retinopathy worsening with rapid glucose lowering (rare).
- Medullary thyroid carcinoma class signal from rodent studies - human relevance uncertain but contraindicated in MTC/MEN2 history.
- Hypoglycemia in patients on insulin or sulfonylureas.
- Long-term safety beyond Phase 3 trial duration not established.
- CV outcomes trials ongoing.
Pharmacokinetics
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.
Regulatory status
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.
Put it to work
Calculate, log & track
Open Mazdutide straight into OnePin with your vial and dose pre-filled, then let it handle the syringe math and remind you before the vial runs out.
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The guide & community
The complete Mazdutide walkthrough, real protocol discussion and coaching live inside the BlessUp community on Skool.
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