Survodutide

Metabolic

Also known as BI 456906

Glucagon and GLP-1 receptor dual agonist. Investigational.

Read this first

The published half-life is contradictory across sources. Curves for this compound are less reliable than for the approved drugs.

How it works

Fully activates the GLP-1 receptor but only partially activates the glucagon receptor at therapeutic exposures. The glucagon arm raises energy expenditure and drives the liver-fat effect that the MASH programme is built on.

Subcutaneous

In the body

Half-life

4.2 days

Time to peak

30 h

90% gone after

13.8 d

Builds up to

1.45×

Steady state after about 21.1 d at once weekly.

Shape of a single dose, modelled as one compartment with first-order absorption. The peak is normalised to 100% because bioavailability and volume of distribution are not published for most of these compounds.

Roughly 4 days, from a secondary review. Note the manufacturer's own trial protocol states 10 to 15 hours, which is inconsistent with weekly dosing and a 28-day residual effect period, and appears to be an error. Treat this curve as provisional.

Doses

300 mcg, 6 mgonce weeklyClinical trial

Phase 2 MASH escalation to 6 mg

NCT04771273 protocol, Table 4.1.4:1 · 46 weeks total

wk 1, 2300 mcg2 weeks
wk 3, 4600 mcg2 weeks
wk 5, 6900 mcg2 weeks
wk 7, 81.2 mg2 weeks
wk 9, 101.8 mg2 weeks
wk 11, 122.4 mg2 weeks
wk 13, 143 mg2 weeks
wk 15, 163.6 mg2 weeks
wk 17, 184.2 mg2 weeks
wk 19, 204.8 mg2 weeks
wk 21, 225.4 mg2 weeks
wk 23, 466 mg24 weeks

Two weeks per step throughout. Phase 3 deliberately slowed this down after gastrointestinal effects clustered in the escalation phase.

Side effects

Nausea in about two thirds of participants at maintenance doses
Vomiting up to 48%, diarrhoea up to 56%
Discontinuation for adverse events 16 to 27%, concentrated in the escalation phase rather than maintenance
Cholelithiasis reported at the higher doses

Cautions

Not an approved medicine. No label and no verified supply.

Status

Investigational. Holds FDA Breakthrough Therapy designation for non-cirrhotic MASH. Phase 3 SYNCHRONIZE trials are complete; not yet filed.

Sources

Reference information for personal record-keeping. Not medical advice, and not a recommendation to use any of these compounds.