Survodutide — Research, Dosing & Price Guide

Survodutide (BI 456906) is a dual glucagon/GLP-1 receptor agonist developed by Boehringer Ingelheim. Unlike tirzepatide (GLP-1/GIP), survodutide pairs GLP-1 receptor agonism with glucagon receptor agonism, specifically targeting hepatic fat metabolism and energy expenditure. It has shown remarkable efficacy for both obesity and MASH (metabolic dysfunction-associated steatohepatitis), with Phase II data demonstrating up to 19% weight loss and dramatic liver fat reduction.

Survodutide activates two receptors: the GLP-1 receptor and the glucagon receptor (GCGR). The GLP-1R component provides appetite suppression, improved glucose-dependent insulin secretion, and slowed gastric emptying — mechanisms well established by semaglutide. The glucagon component adds unique metabolic effects: it increases hepatic fat oxidation, stimulates energy expenditure through thermogenesis, promotes amino acid catabolism, and enhances ketogenesis. Glucagon traditionally raises blood glucose, but the concurrent GLP-1R activation offsets this with improved insulin sensitivity and secretion, creating a metabolic environment where fat is preferentially mobilized and oxidized while glycemia remains controlled. This dual mechanism is particularly potent for reducing liver fat — glucagon directly activates hepatic lipid oxidation pathways (CPT1α, PPARα) while GLP-1 reduces lipogenesis and hepatic inflammation.

• Phase II obesity trial (2024, NEJM) showed 18.7% body weight loss at the 4.8 mg dose over 46 weeks
• Phase II MASH trial demonstrated up to 83% relative reduction in liver fat content measured by MRI-PDFF
• 47% of MASH patients achieved histological resolution of steatohepatitis with survodutide vs. 14% placebo
• The glucagon component produced greater reductions in liver fat than seen with GLP-1-only agents
• Survodutide improved ALT and AST liver enzymes significantly, suggesting hepatoprotective effects
• Energy expenditure measurements showed survodutide increased resting metabolic rate compared to GLP-1-only treatment

• Phase II trial doses: escalation from 0.3 mg to target doses of 2.4 mg, 4.8 mg, or 6 mg weekly
• Dose escalation over 16–20 weeks with incremental increases every 4 weeks
• Administered as a subcutaneous injection once weekly
• No established clinical or off-label protocol for non-trial use
• GI side effect management requires slow, careful dose titration
• Inject in abdomen, thigh, or upper arm; rotate sites

Known Side Effects

• Nausea (up to 50% of participants in trials), the most common and dose-limiting side effect
• Vomiting and diarrhea, particularly during dose escalation
• Decreased appetite — pharmacological effect but can be excessive
• Increased heart rate (2–5 bpm) observed in trial participants
• Injection site reactions
• Potential for hypoglycemia when combined with insulin or sulfonylureas
• Discontinuation rate due to GI side effects was 5–10% in trials

Safety Profile

Survodutide is investigational and not yet FDA-approved. Phase II data show a safety profile broadly consistent with the GLP-1 class, with GI side effects being the primary tolerability concern. The glucagon component raises theoretical concerns about hyperglycemia, but this has been well-controlled by the GLP-1 component in trials. As with all GLP-1 class agents, the medullary thyroid carcinoma boxed warning from rodent studies applies. Pancreatitis monitoring is advised. Liver safety data has been favorable — in fact, liver function improved in MASH trials. Cardiovascular outcome trials are ongoing. Not recommended during pregnancy. Long-term safety data beyond 46 weeks is limited.

Week 1–4: Mild appetite reduction during low-dose escalation. GI side effects (nausea, occasionally vomiting) are common but typically manageable. Weight loss of 1–3% possible. Week 5–12: Appetite suppression strengthens with dose escalation. Weight loss accelerates to 1–2 lbs per week. Liver fat begins reducing significantly (measurable by imaging at 12 weeks). Week 12–24: Substantial weight loss (10–15%) and dramatic liver fat reduction (50–80% relative reduction). Metabolic markers (HbA1c, liver enzymes, triglycerides) improve. Week 24–46: Continued weight loss approaching 15–19% at highest doses. Liver histology improvements in MASH patients. GI side effects generally plateau and may diminish.

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