Mazdutide

Mazdutide (IBI362/LY3305677) is a first-in-class dual glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist, and a synthetic analog of oxyntomodulin. Unlike tirzepatide which targets GIP/GLP-1, mazdutide uniquely combines GLP-1's appetite suppression with glucagon's ability to stimulate thermogenesis and increase energy expenditure. Phase 3 trials (GLORY-1, GLORY-2) have demonstrated up to 20% weight loss, with recent head-to-head trials showing superiority over semaglutide for both glycemic control and weight reduction in patients with type 2 diabetes and obesity.

• Severe Obesity Management
• Metabolic Syndrome Improvement
• Liver Fat Reduction

Up to 20% body weight loss, superior glycemic control vs semaglutide, increased energy expenditure via glucagon receptor activation, improved cardiometabolic markers (BP, lipids, liver fat), once-weekly convenience

Dual agonist of GLP-1 and glucagon receptors. GLP-1 activation: stimulates insulin release, suppresses glucagon, slows gastric emptying, reduces appetite via hypothalamic signaling. Glucagon activation: increases energy expenditure and thermogenesis, improves hepatic fat metabolism. The dual mechanism provides synergistic weight loss effects while GLP-1 counteracts glucagon's glucose-raising effects.

Research protocols from published literature — not dosing recommendations.

• Semaglutide — Avoid Combination: Both are GLP-1 agonists - combining increases hypoglycemia and severe GI side effect risk. Head-to-head trials show mazdutide is superior; no benefit to combining
• Tirzepatide — Avoid Combination: Both target GLP-1 receptor - combining creates additive effects on GI symptoms and hypoglycemia risk without proven additional benefit
• Liraglutide — Avoid Combination: Another GLP-1 agonist - dual therapy contraindicated due to additive receptor activation and adverse effect risk
• Insulin — Monitor Closely: May require significant insulin dose reduction due to improved glucose control. Monitor blood glucose carefully to prevent hypoglycemia
• Sulfonylureas — Monitor Closely: Increased hypoglycemia risk when combined. Dose reduction of sulfonylureas may be necessary
• Metformin — Synergistic: Complementary mechanisms for diabetes management. Clinical trials allowed stable metformin use with mazdutide showing enhanced efficacy
• CJC-1295 — Compatible: Growth hormone support may help preserve muscle mass during rapid weight loss phase
• Ipamorelin — Compatible: May help maintain metabolic rate and muscle preservation during caloric restriction
• BPC-157 — Compatible: No known interactions, may support gut health and potentially reduce GI side effects
• Oral Contraceptives — Monitor Timing: GLP-1 agonists may affect absorption of oral medications due to delayed gastric emptying. Take oral contraceptives 1 hour before or 4 hours after mazdutide
• Levothyroxine — Monitor Timing: Delayed gastric emptying may affect thyroid hormone absorption. Monitor thyroid function and adjust timing if needed

Supplies:

• Mazdutide lyophilized powder vial
• Bacteriostatic water (BAC) for injection
• Insulin syringes (29-31 gauge, 0.5ml or 1ml)
• Alcohol prep pads
• Sterile work surface
• Refrigerator for storage (2-8°C)

1. 1Remove mazdutide vial from freezer/refrigerator and allow to reach room temperature (15-20 minutes)
2. 2Clean vial top with alcohol swab using circular motion, allow to air dry completely
3. 3Calculate appropriate reconstitution volume based on desired concentration
4. 4Draw calculated amount of bacteriostatic water into syringe, remove air bubbles
5. 5Insert needle at 45-degree angle against vial wall, NOT directly into powder
6. 6Slowly inject BAC water down the side of the vial - drop by drop to prevent foaming
7. 7Remove needle and gently swirl vial in circular motion - NEVER shake vigorously
8. 8Allow solution to sit 2-3 minutes if cloudiness persists, then swirl gently until completely clear
9. 9Final solution should be completely clear and colorless - discard if cloudy or contains particles
10. 10Label vial with reconstitution date and concentration
11. 11Store reconstituted solution at 2-8°C, use within 30 days

Week 1-2: Appetite reduction, possible mild nausea, decreased portion sizes. Week 3-4: Early weight loss begins (1-2%), improved satiety after meals. Week 4-8: Dose escalation phase, GI symptoms typically improving, 3-5% weight loss. Week 8-16: Steady weight loss continues (7-12%), energy expenditure effects evident. Week 16-32: Significant weight reduction (12-17%), metabolic markers improving. Week 32-60: Peak effects (up to 20% weight loss), sustained improvements in BP, lipids, glucose. Note: Weight loss continues without plateau through 60 weeks in clinical trials. Diabetic patients: Blood glucose improvements within 1-2 weeks, HbA1c reduction by week 12-20.

Start with lowest dose and escalate gradually every 4 weeks to minimize GI side effects. GI symptoms (nausea, diarrhea, vomiting) are most common - typically mild-moderate and improve over time. Increased heart rate (5-17 bpm) observed but not associated with cardiac events in trials. Monitor for signs of pancreatitis - severe persistent abdominal pain radiating to back. Caution with personal/family history of medullary thyroid carcinoma or MEN2 syndrome (class warning for GLP-1 agonists). If taking insulin or sulfonylureas, monitor blood glucose closely and reduce doses as needed. Not recommended during pregnancy or breastfeeding - insufficient safety data. Stay well hydrated, especially during initial weeks when GI symptoms may occur.

Start with lowest dose and escalate gradually every 4 weeks to minimize GI side effects. GI symptoms (nausea, diarrhea, vomiting) are most common - typically mild-moderate and improve over time. Increased heart rate (5-17 bpm) observed but not associated with cardiac events in trials. Monitor for signs of pancreatitis - severe persistent abdominal pain radiating to back. Caution with personal/family history of medullary thyroid carcinoma or MEN2 syndrome (class warning for GLP-1 agonists). If taking insulin or sulfonylureas, monitor blood glucose closely and reduce doses as needed. Not recommended during pregnancy or breastfeeding - insufficient safety data. Stay well hydrated, especially during initial weeks when GI symptoms may occur.

Mazdutide should be stored at Lyophilized: -20°C long-term; Reconstituted: 2-8°C use within 30 days.