Survodutide

Survodutide (BI 456906) is an investigational dual glucagon receptor (GCGR) and GLP-1 receptor (GLP-1R) agonist designed for once-weekly subcutaneous administration. This 29-amino acid peptide with C18 fatty acid acylation represents a novel approach to metabolic disease treatment by simultaneously targeting both energy intake reduction (via GLP-1R) and energy expenditure increase (via GCGR), demonstrating robust efficacy in clinical trials for obesity and metabolic dysfunction-associated steatohepatitis (MASH).

• Obesity Without Diabetes
• Obesity With Type 2 Diabetes
• Sustained Weight Management

Dual mechanism for superior weight loss, once-weekly dosing, demonstrated efficacy in obesity/MASH/T2D, well-established safety profile from Phase 2/3 trials

Balanced agonism of glucagon receptors (increases energy expenditure, hepatic fat oxidation) and GLP-1 receptors (reduces appetite, slows gastric emptying) with ~6-day half-life enabling weekly dosing

Peak plasma concentration: 2 days. Elimination half-life: 6.5 days. Largely cleared by: ~32.5 days.

Research protocols from published literature — not dosing recommendations.

• Semaglutide/Tirzepatide — Use Caution: Both are GLP-1 receptor agonists - combining may lead to excessive GLP-1 activation and increased gastrointestinal side effects. Not recommended without medical supervision.
• Metformin — Compatible: No direct interaction. Can be used together as demonstrated in Phase 2 trials with type 2 diabetes patients on metformin background therapy.
• SGLT2 Inhibitors — Compatible: No known interactions. Phase 3 trials allow concurrent use of SGLT2 inhibitors with appropriate monitoring of glycemic control.
• Sulfonylureas — Monitor Combination: Risk of hypoglycemia when combined. Monitor blood glucose closely and consider sulfonylurea dose reduction if needed.
• Insulin — Dose Dependent: May require insulin dose adjustment due to improved glycemic control. Start with lower insulin doses and titrate based on glucose monitoring.
• Oral Contraceptives — Requires Timing: Delayed gastric emptying may affect absorption. Take oral contraceptives at least 1 hour before survodutide injection.
• Warfarin — Monitor Combination: May affect warfarin absorption due to delayed gastric emptying. Monitor INR more frequently when initiating or changing survodutide dose.
• Other Glucagon Agonists — Avoid Combination: Risk of excessive glucagon receptor activation. Do not combine with other glucagon receptor agonists.

Supplies:

• Survodutide lyophilized powder vial
• Bacteriostatic water (typically 1-2mL)
• Insulin syringe (29-31 gauge)
• Alcohol swabs
• Sterile mixing needle (if separate from injection)

1. 1Remove survodutide vial from refrigerator and allow to reach room temperature (15-30 minutes)
2. 2Clean rubber stoppers of both vials with alcohol swabs
3. 3Draw prescribed amount of bacteriostatic water into syringe
4. 4Insert needle into survodutide vial at 45-degree angle
5. 5Slowly inject BAC water down the side of vial to minimize foaming
6. 6Gently swirl vial - do not shake vigorously
7. 7Allow to sit for 2-3 minutes for complete dissolution
8. 8Solution should be clear to slightly opalescent without particles
9. 9Store reconstituted solution in refrigerator immediately

Week 1-4: Possible nausea, reduced appetite - most common during dose escalation. Week 4-8: Initial weight loss begins, improved satiety between meals. Week 8-16: Progressive weight loss, potential improvement in energy levels. Week 16-24: Approaching steady-state levels, more consistent effects. Week 24+: Sustained weight loss, metabolic improvements become more apparent. Long-term: Average 15-19% weight loss at higher doses by week 46.

Common GI side effects: nausea (40-66%), diarrhea (25-49%), vomiting (15-41%). Most GI effects occur during dose escalation - use flexible dosing if needed. Heart rate may increase slightly (mean 2-5 bpm) - monitor if cardiac conditions. Not recommended in pregnancy or breastfeeding - use contraception. No dose adjustment needed for hepatic impairment including cirrhosis. Monitor blood glucose if on diabetes medications - may need adjustment.

Common GI side effects: nausea (40-66%), diarrhea (25-49%), vomiting (15-41%). Most GI effects occur during dose escalation - use flexible dosing if needed. Heart rate may increase slightly (mean 2-5 bpm) - monitor if cardiac conditions. Not recommended in pregnancy or breastfeeding - use contraception. No dose adjustment needed for hepatic impairment including cirrhosis. Monitor blood glucose if on diabetes medications - may need adjustment.

Survodutide should be stored at Refrigerate at 2-8°C, protect from light, use within 4 weeks of reconstitution.