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Survodutide

Also known as BI 456906

Experimental dual glucagon and GLP-1 receptor agonist for obesity and MASH.

early-clinical Metabolic & weight research chemical

At a glance

Category
Metabolic & weight
Status
research chemical
Route
subcutaneous, once weekly
Half-life
approximately 6-7 days in humans; steady state after approximately 5 weeks of weekly dosing
Onset
weight loss from a few weeks onwards; in phase 2 weight was still falling up to week 46
Sequence
Acylated 29-amino-acid peptide derived from glucagon, with a fatty acid side chain for albumin binding; sequence not publicly published in standardised form

Not registered. In phase 3 trials (the SYNCHRONIZE programme of Boehringer Ingelheim and Zealand Pharma) for obesity, and in clinical research for MASH. In October 2024 the FDA granted survodutide Breakthrough Therapy designation for adults with non-cirrhotic MASH and moderate or advanced fibrosis (stages 2 or 3), alongside the start of the phase 3 LIVERAGE and LIVERAGE-Cirrhosis trials 6.

Doping status: Prohibited (WADA S0, non-approved substances)

Checked against the WADA 2026 Prohibited List. For a specific product and country, Global DRO is the lookup athletes are expected to use — the List names substances, not brand names.

Mechanism of action

Survodutide activates two receptors: the glucagon receptor and the GLP-1 receptor. Via the GLP-1 receptor it suppresses appetite centrally, stimulates glucose-dependent insulin secretion and slows gastric emptying — the same profile as semaglutide.

The glucagon receptor component acts mainly on the liver and adipose tissue: increased energy expenditure, stimulated lipolysis and fatty acid oxidation, and a reduction in intrahepatic fat. This combination of reduced intake (GLP-1) and increased expenditure (glucagon) explains why the compound is also being studied in MASH.

Unlike retatrutide, survodutide contains no GIP component. The glucagon component is relatively strong, which appears favourable for the hepatic effect but at the same time increases the risk of raised heart rate and of raised glucose. The optimal ratio between the two receptor activities is an open question.

What the research shows

The evidence comes from phase 1 and phase 2 studies with a few hundred participants each. The phase 3 results of the SYNCHRONIZE programme had not been fully published when this text was written. The reported weight effects are comparable to or slightly greater than those of semaglutide, but there is as yet no registration and no long-term safety profile.

Research in humans

The phase 2 dose-finding study (Lancet Diabetes & Endocrinology 2024, n=386 adults with BMI ≥ 27 without type 2 diabetes, 46 weeks) reported a mean weight loss of 14.9% at the 4.8 mg per week dose versus 2.8% with placebo in the primary analysis, which was based on the dose assigned at randomisation. A prespecified sensitivity analysis based on the dose participants actually received during maintenance, counting on-treatment data only, gave 18.7% versus 2.3% — a larger figure that circulates widely, but one that excludes much of the dropout during rapid escalation and is therefore the more flattering of the two 1. A phase 2 study in MASH with fibrosis reported MASH resolution without worsening of fibrosis in a considerably higher proportion than with placebo. A pharmacokinetic study in liver cirrhosis has also been published.

Animal and lab research

Preclinical models support the combined effect on energy intake and energy expenditure and the favourable effect on hepatic steatosis. As with all GLP-1 receptor agonists, thyroid C-cell effects in rodents are a class-wide point of attention.

Caveats. The studies were funded and conducted by Boehringer Ingelheim. The phase 2 obesity study had a considerable dropout rate, largely due to gastrointestinal side effects with rapid titration 1. Rare side effects and long-term risks have not been established. There are no published cardiovascular outcome trials; the CVOT is still running. Head-to-head studies against semaglutide or tirzepatide are lacking.

What it is used for

  • Studied for obesity and overweight with comorbidity
  • Studied for MASH (metabolic dysfunction-associated steatohepatitis) with moderate or advanced fibrosis, and for MASH cirrhosis, in the phase 3 LIVERAGE programme 6
  • Studied for type 2 diabetes with overweight
  • Used outside trial settings via the grey market; this use is neither regulated nor controlled

Dosing

Dose
0.6 mg to 6.0 mg per week (doses as studied in phase 2 and phase 3)
Frequency
once weekly
Route
Subcutaneous
Duration
46 weeks in phase 2; the optimal treatment duration has not been established
  • In the phase 2 study titration started at 0.3-0.6 mg per week with increases every 2 weeks to final maintenance doses of 0.6, 2.4, 3.6 or 4.8 mg per week; the rapid titration was accompanied by considerable gastrointestinal dropout.
  • In the phase 3 programme titration goes to 3.6 mg or 6.0 mg per week over a longer build-up period, with the option of dose flexibility in case of tolerability problems.
  • There is no approved dosing schedule. What is set out here is a description of study doses, not a usage instruction.
  • Doses circulating in online user protocols have not been clinically validated.
  • Survodutide is not licensed anywhere, yet it is sold as lyophilised powder in vials online and is reconstituted and self-injected. Trial participants receive a sponsor-prepared solution in a prefilled pen; the powder is a separate, unapproved supply route and none of the study titration schedules have been validated for it.
  • The milligram-versus-microgram trap is the single most likely way someone is harmed with this compound, and the small starting doses make it worse. A 0.6 mg starting dose is 600 micrograms — a factor of a thousand separates the two units — and 'units' on an insulin syringe is a volume (1 unit = 0.01 ml), not a dose, so the same unit count means a different milligram amount at every concentration. The FDA's compounding risk alert of 26 July 2024, describing this exact vial-and-syringe failure mode for semaglutide, records patients administering five to twenty times the intended dose; patients told to inject 5 units injected 50 instead 4.
  • Grey-market powder carries no guarantee of identity, purity, sterility or actual milligram content, so the number on the label may not be the number in the vial, and any calculation is only as good as that label. There is no licensed survodutide product anywhere against which a vial could be compared.
  • The trial escalation schedules exist because gastrointestinal effects are dose-limiting, and survodutide makes the point unusually plainly: in the phase 2 obesity study the rapid two-weekly titration produced considerable dropout, and gastrointestinal adverse events were the main reason participants left the trial. The phase 3 programme lengthened the build-up in response. Starting at a maintenance dose rather than titrating is how people end up vomiting for days and dehydrated, and with a half-life of six to seven days an overdose does not resolve overnight.
  • A self-dosing practice circulates and is recorded in the protocols section below as a social fact, not a validated schedule. The doses passed around are copied either from the trial titration or, by analogy, from the tirzepatide and retatrutide ladders that self-dosers already run, and there is no agreement on where to stop: some settle at the phase 3 target of 3.6 mg, others chase the 4.8 mg used in phase 2 or the 6.0 mg upper target. None of it has a published basis for grey-market material.

These figures describe what the literature and published protocols report. They are not advice and not a dosing instruction.

Protocols

Registered trial up-titration to 3.6 mg weekly (NCT07206290)

published trial

Source: ClinicalTrials.gov record NCT07206290 (survodutide in kidney disease, Boehringer Ingelheim)

Up-titration phase, 16 weeks0.3 mg, then 0.6 mg, 1.2 mg, 2.4 mg and 3.6 mg subcutaneously once weekly
Maintenance phase, 20 weeks3.6 mg subcutaneously once weekly

The registry states the sequence of doses and the total length of the up-titration phase, not how long is spent at each step. The phase 3 obesity programme uses a longer scheme reaching 3.6 mg or 6.0 mg, but its published design paper describes that escalation only in general terms, so it is not reproduced here.

Commonly reported user schedule (weekly subcutaneous)

user protocol — not validated

Source: User reports on peptide and GLP-1 forums together with vendor vial labelling

This is not a validated schedule. It is a pattern that circulates among users and sellers, reproduced because it is what people actually follow — not because it has been tested. No trial established these doses, this interval or this duration, and nobody is checking what is in the vial. Treat every number below as an assertion, not a finding.

Reported startcommonly 0.3-0.6 mg once weekly, copied from the trial starting dose or from a familiar GLP-1 starting point
Reported escalationstepped up every 2-4 weeks, mirroring the trial titration and the tirzepatide/retatrutide ladders
Reported maintenanceno consensus: 3.6 mg, 4.8 mg or 6.0 mg once weekly are all reported as targets
Reported cyclerun continuously; no consistent off-period is described

These figures come from user reports and vendor labelling and have no published pharmacokinetic or safety basis for survodutide used this way. The disagreement over the maintenance target — 3.6 versus 4.8 versus 6.0 mg — is itself the finding: people are copying different arms of different trials, or extrapolating from other dual agonists, because nothing published tells a self-doser what to aim for. The small starting doses make the milligram-versus-microgram error the most likely way to be harmed (0.6 mg is 600 mcg; a syringe 'unit' is a volume, not a dose), and the vials on sale range across 5, 10 and 20 mg, so a unit count copied from someone else's protocol delivers a different milligram amount at each concentration. The FDA has documented five- to twentyfold self-dosing errors of exactly this kind with compounded GLP-1 products 4.

Schedules are reproduced as their source states them. Units, IU and milligrams explains why the figures are not interchangeable between products.

Reconstitution

Vial sizes
5 mg, 10 mg, 20 mg
Solvent
bacteriostatic water (0.9% benzyl alcohol)
Storage
No approved storage instruction exists, because there is no approved product. Sellers typically advise storing the powder frozen and protected from light and refrigerating the reconstituted solution, but no stability data for this material have been published, and the FDA has received complaints of GLP-1 products arriving warm or inadequately cooled.

Worked example

Two supply routes, kept apart. Clinical trials use a ready-to-use solution in a prefilled pen and participants reconstitute nothing; there is no registered product and no validated reconstitution protocol. What circulates online is lyophilised powder, reconstituted and measured by the buyer, and the arithmetic for such a vial runs: 10 mg vial + 2 ml bacteriostatic water = 5 mg/ml. A 0.6 mg (600 mcg) starting dose is 0.12 ml, which is 12 units on a U100 insulin syringe; a 4.8 mg dose from the same vial is 0.96 ml, or 96 units. Reconstitute a 5 mg vial with the same 2 ml and the concentration halves to 2.5 mg/ml, at which 12 units delivers 0.3 mg — half the intended dose, from an identical syringe reading.

Vial strengths are not standardised between sellers: 5, 10 and 20 mg all circulate, a fourfold spread that is invisible from the outside, so concentration must be recalculated for every vial and a unit figure copied from another protocol is meaningless. The worked example is descriptive arithmetic, not a protocol, and it changes nothing about the starting material, whose identity, purity, sterility and actual milligram content are unverified.

Work it out for Survodutide

Safety

Side effects

  • Nausea, vomiting, diarrhoea and constipation — very common, dose-dependent and most pronounced during titration; in phase 2 the main reason for trial dropout
  • Reduced appetite, dyspepsia, abdominal pain
  • Increased heart rate, attributed to the glucagon component
  • Injection site reactions
  • Fatigue and headache
  • Loss of fat-free mass with rapid weight loss
  • Class effects of GLP-1 agonists (pancreatitis, gallbladder disorders, gastroparesis) are to be expected but cannot be reliably quantified in the limited study population
  • Rare and late side effects are unknown
  • Overdose from a dosing error with reconstituted powder: the adverse events the FDA recorded for this failure mode were gastrointestinal effects, fainting, headache, migraine, dehydration, acute pancreatitis and gallstones, some requiring hospitalisation 4. With a half-life of six to seven days, the effects of a tenfold error run for days rather than hours
  • Injection-site infection and abscess from non-sterile technique or non-sterile starting material

Do not use if

  • Personal or family history of medullary thyroid carcinoma (MTC) — class contraindication for GLP-1 receptor agonists
  • Multiple endocrine neoplasia type 2 (MEN2)
  • History of pancreatitis
  • Pregnancy, breastfeeding and wish to conceive
  • Serious gastrointestinal disorders including gastroparesis
  • Existing tachycardia or cardiac arrhythmias — given the observed increase in heart rate
  • Use outside clinical trials: no body guarantees the identity, strength or sterility of the product
  • Reconstituting and measuring unregulated powder without being able to do the milligram-to-unit conversion reliably. Tenfold errors at this step are the most frequently documented mechanism of harm with drugs in this class, and the FDA has recorded adverse events, some requiring hospitalisation, from them 4
  • Any assumption that a grey-market vial contains what its label states. There is no licensed survodutide product anywhere, so no verified reference material exists and the label is the only claim there is

Interactions

Not systematically studied. On the basis of the mechanism of action the same points apply as for registered GLP-1 agents: delayed gastric emptying can affect the absorption of oral medication, and combination with insulin or sulfonylureas increases the risk of hypoglycaemia. The glucagon component can raise blood glucose, which complicates the titration of antidiabetic drugs. Pharmacokinetics in liver cirrhosis has been studied and published.

Sources