Survodutide Guide: Evidence & Sourcing

Survodutide at a glance

What it is

Survodutide (development code BI 456906), an investigational once-weekly glucagon receptor and GLP-1 receptor dual agonist; PubChem CID 168429725, molecular formula C192H289N47O61, molecular weight approximately 4,232

Researched for

Obesity (phase 3, published), type 2 diabetes, metabolic dysfunction-associated steatohepatitis and steatotic liver disease including cirrhosis, and cardiovascular safety

Half-life

Consistent with once-weekly dosing, but we could not source a specific published half-life figure from the trial reports checked. A phase 1 study found AUC and Cmax similar in people with cirrhosis and matched healthy individuals, with no pharmacokinetic dose adjustment required

Regulatory status

Not approved anywhere. DailyMed returned zero structured product labels for survodutide and openFDA's Drugs@FDA endpoint returned no match. Investigational; research use only

Educational reference. This page does not publish dose ranges or reconstitution arithmetic.

What it is / mechanism

Survodutide is a synthetic peptide agonist at two receptors at once: the glucagon receptor (GCGR) and the glucagon-like peptide-1 receptor (GLP-1R). Its development code is BI 456906, and it is catalogued in PubChem as CID 168429725 with molecular formula C192H289N47O61 and a molecular weight of about 4,232 — roughly 4.6 times the mass of a small research peptide like BPC-157, and about the size class you would expect for a lipidated, albumin-binding, long-acting analogue dosed once a week rather than daily. The dual-agonist design is what distinguishes it from the semaglutide class. GLP-1 receptor agonism is the familiar half: slowed gastric emptying, increased satiety, glucose-dependent insulin secretion. Glucagon receptor agonism is the addition, and it is a deliberate reversal of the intuition most people bring to glucagon, which they know as the hormone that raises blood sugar. In the dual-agonist rationale, glucagon-receptor signalling contributes increased energy expenditure and direct hepatic effects on fat handling, while the GLP-1 arm supplies the appetite suppression and offsets glucagon's glycaemic effect. That combination is the reason the liver programme exists alongside the obesity programme. Survodutide is in phase 3 for metabolic dysfunction-associated steatohepatitis and steatotic liver disease as well as for obesity, and a mediation analysis published in Hepatology in 2026 explicitly asked whether its liver effects are weight-reduction-dependent or independent of weight loss — a question that only arises for a compound with a direct hepatic mechanism. It is also the reason the flagship obesity trial excluded people with diabetes. SYNCHRONIZE-1 enrolled adults with obesity without diabetes, and type 2 diabetes was studied separately in SYNCHRONIZE-2. When a programme splits its populations that way, the split is information: it says the sponsor wanted the glycaemic question answered in its own trial rather than inside the weight trial.

Researched effects

Survodutide is one of the few compounds in this library where the honest answer to "what does it do" comes from a published phase 3 trial rather than from inference, so it is worth quoting the numbers rather than summarising them. SYNCHRONIZE-1 (NCT06066515) randomised 725 adults with a BMI of 30 or higher, or 27 or higher with at least one obesity-related complication and without diabetes, in a 1:1:1 ratio to once-weekly subcutaneous survodutide titrated up to 3.6 mg, up to 6.0 mg, or placebo, all alongside lifestyle counselling. Mean age was 47.1 years, mean BMI 37.9, mean body weight 108.8 kg, and 40.6% of participants were men. At week 76, mean body-weight change from baseline was -12.2% (95% CI -13.6 to -10.8) in the 3.6 mg group, -13.0% (95% CI -14.4 to -11.6) in the 6.0 mg group, and -5.4% (95% CI -6.9 to -4.0) on placebo. Weight reduction of at least 5% was achieved by 72.6%, 71.9% and 46.3% of participants respectively, with p<0.001 for both comparisons against placebo. The results were published in the New England Journal of Medicine on 7 June 2026 (PMID 42253238) and funded by Boehringer Ingelheim. Three things in that paragraph deserve to be pulled out, because they are the parts most likely to be dropped when the number gets repeated. First, the placebo group lost 5.4%. The drug-attributable difference is therefore about 6.8 percentage points at 3.6 mg and 7.6 at 6.0 mg — real, statistically robust, and roughly half the headline figure. When you see "13% weight loss" quoted for survodutide, that figure includes everything the placebo arm also achieved on lifestyle counselling alone. Second, the two doses barely separated. Going from 3.6 mg to 6.0 mg — a 67% larger maintenance dose — bought 0.8 percentage points of additional mean weight change, and the proportion reaching 5% loss was fractionally lower on the higher dose (71.9% versus 72.6%). On this evidence the dose-response curve for weight is close to flat across the tested maintenance range. Third, the side-effect curve is not flat. Gastrointestinal adverse events occurred in 80.9% of the 3.6 mg group, 89.7% of the 6.0 mg group and 47.9% of placebo. So the step from 3.6 mg to 6.0 mg added about nine percentage points of gastrointestinal adverse events for less than one point of weight change. That is a genuinely useful thing to know and it is visible only if you read both halves of the results. The liver programme has now also reported: SYNCHRONIZE-MASLD, a randomised, double-blind, placebo-controlled phase 3 trial in adults with obesity and metabolic dysfunction-associated steatotic liver disease, was published in Nature Medicine in 2026 (PMID 42252333). None of this is a promise of outcome, and none of it applies to research-market material, which is not the trial product.

Research timeline

Dated milestones taken from the primary records: the molecule's discovery, its first registered human study, the trials that shaped the evidence and the regulatory decisions. Each entry links to the record it comes from.

1. Dec 2022Boehringer Ingelheim scientists describe BI 456906, a peptide that activates both the glucagon and GLP-1 receptors and carries a fatty-acid chain to last a week; in mice it reduced body weight more than semaglutide, through higher energy use and lower food intake. PMID 36356832
2. Apr 2023Phase 1 studies in people report body weight 13.8% below placebo after 16 weeks in one schedule; adverse events rose with dose, and in one part 7.5% of participants stopped because of a cardiac or vascular adverse event. PMID 36527386
3. Mar 2024The phase 2 obesity trial (387 adults, 46 weeks) reports weight loss of up to 14.9% against 2.8% with placebo; only about 60% completed the treatment period, and gastrointestinal events affected 75% on survodutide against 42% on placebo. PMID 38330987
4. Jul 25, 2024A phase 2 biopsy trial in fatty-liver inflammation with fibrosis (MASH, 293 participants), published in the New England Journal of Medicine, reports MASH improving without worsening fibrosis in up to 62% on survodutide against 14% on placebo; nausea affected 66% against 23%. PMID 38847460
5. Aug 2026The phase 3 SYNCHRONIZE-MASLD trial (216 adults with obesity and at-risk fatty liver, 48 weeks, sites in the US and Spain) reports liver fat down by at least 30% in 68.5% on survodutide against 28.6% on placebo, and body weight down 8.7% against 1.4%. PMID 42252333
6. Aug 20, 2026SYNCHRONIZE-1 (725 adults with obesity, no diabetes, 76 weeks) is published in the New England Journal of Medicine: body weight fell 13.0% at the higher dose against 5.4% with placebo; gastrointestinal symptoms affected 89.7% against 47.9%. PMID 42253238

Records checked Oct 3, 2026

Claims at a glance

The claims most often made about this compound, each with the strongest kind of evidence we found for it. The grade says what was studied, not whether the claim is true; the line beside it says what that study showed.

• Causes substantial weight lossHuman, randomised trial. In a 76-week phase 3 trial of 725 adults with obesity, weight fell about 12–13% against 5.4% on placebo, counting people who stopped treatment. PMID 42253238
• Reduces liver fatHuman, randomised trial. A 48-week phase 3 trial in fatty liver disease met both main goals; how big the effect looks depends on whether people who stopped are counted. PMID 42252333
• Improves fatty-liver inflammation (MASH) and fibrosisHuman, randomised trial. In a 48-week phase 2 biopsy trial, 43–62% improved against 14% on placebo; the highest dose did worse than the middle one. Phase 3 histology has not reported. PMID 38847460
• Lowers blood sugar in type 2 diabetesHuman, randomised trial. One 16-week phase 2 trial lowered HbA1c against placebo, in the range of an open-label semaglutide arm; the diabetes phase 3 has published only its baseline. PMID 38095657
• Boosts metabolism and energy expenditureAnimal studies only. Higher energy expenditure was shown in obese mice; the human study built to measure it had not reported, so the claim in people is an extrapolation. PMID 36356832
• Protects the heartNo study found. The 5,531-person heart trial finished in June 2026 with no results posted or published; it was designed to show the drug is not worse for the heart, not that it helps. NCT06077864

The reasoning behind each grade, study by study, is in this guide's Benefit & Outcome Review.

Grades checked Oct 6, 2026

Half-life & pharmacokinetics

Survodutide is dosed once weekly in every trial in its programme, which places its half-life firmly in the multi-day range characteristic of albumin-binding, lipidated peptide analogues. Beyond that, we are not going to publish a number. We could not source a specific published elimination half-life for survodutide from the trial reports checked for this page, and there is no approved label to take one from — DailyMed holds no structured product label for this compound and openFDA's Drugs@FDA endpoint returns no match. Figures do circulate in secondary summaries; none of the ones we encountered named the study they came from, and this library's standing rule is that an unattributed pharmacokinetic figure is worth less than a plain statement of what is documented. What is documented, and is more practically informative than a half-life anyway, comes from the phase 1 trial in people with cirrhosis (NCT05296733, Journal of Hepatology 2024, PMID 38857788). After a single 0.3 mg subcutaneous dose, mean area under the curve to infinity and mean Cmax were similar in people with Child-Pugh class A, B or C cirrhosis and in matched healthy individuals, with the 90% confidence intervals for the adjusted geometric mean ratios spanning 1. The authors concluded that survodutide does not require pharmacokinetic-related dose adjustment in cirrhosis. For a compound being developed for liver disease, having that answered in the population with the most impaired clearance is a more useful pharmacokinetic fact than a half-life in healthy volunteers would be. The practical reading: treat this as a once-weekly compound whose exposure is stable enough that even substantial hepatic impairment did not change it materially, and treat any specific half-life figure you encounter as unsourced until someone names the study.

Storage & handling

• Lyophilized (powder): store sealed and refrigerated at 2-8°C, protected from light and moisture; long-term storage is commonly at -20°C or below. Do not use past intended research shelf life.
• Reconstituted (liquid): refrigerate at 2-8°C, protect from light, and avoid freeze-thaw cycles and vigorous shaking.
• A once-weekly compound means a reconstituted vial is entered repeatedly across weeks, which is the case bacteriostatic water exists for — the benzyl alcohol preservative is what makes a multi-entry vial multi-entry. Sterile water carries no preservative and is a single-entry diluent.

Evidence File

The Survodutide Evidence File: 31 Trials, Two Estimands, and the Numbers the Press Releases Dropped

Survodutide is the rare research-market compound with published phase 3 results, which changes what an evidence file is for: not scraping for data, but auditing it. This file reads the complete ClinicalTrials.gov record - including the early trials that a search for the drug's name does not return - and fifteen published abstracts, from the first-in-human study through the 2026 Nature Medicine liver trial. It traces the figures that circulate in marketing copy back to the specific analyses that produced them, documents which completed trials have published nothing, and compares what the protocols actually did against what the research market assumes. Every number was checked against a source fetched on the verification date.

• 33 registry records reviewed; 7 findable only under BI 456906
• 6 circulating figures traced to their originating analysis
• 0 terminated, withdrawn or suspended trials in the registry
• 4 completed phase 3 trials with no published primary result

Sourcing File

The Survodutide Sourcing File: No CAS Number, One Undefined Stereocentre, and What a Real COA Must Show

There is no approved survodutide product anywhere, so every vial on the research market is a synthetic peptide whose identity rests entirely on the certificate that comes with it. This file anchors the compound's identity to its authoritative chemical record - down to which identifiers that record does and does not contain - and works out, number by number, what a mass spectrum and a purity trace of genuine material must look like. It then maps the specific ways a survodutide vial can be wrong, from substitution to salt-form arithmetic, and walks a certificate of analysis line by line, flagging which entries are commonly asserted rather than measured.

• 4 comparator peptides identity-verified against PubChem records
• 7 mislabelling and adulteration modes mapped to the tests that catch them
• 0 CAS or UNII identifiers on the compound's PubChem record
• 1 undefined stereocentre flagged on the authoritative record

Benefit & Outcome Review

Survodutide Benefit and Outcome Review: What Is Proven, What Is Mouse, and What Has Never Been Measured

Survodutide's claims come in three kinds. Some rest on large randomised human trials, including published phase 3 results - rare territory for a research-market peptide. Some rest on mouse experiments that marketing copy quietly promotes into human facts. And some rest on nothing located at all, which this review treats as findings in their own right: each absence is documented with the exact literature search that returned empty. This file grades every major claim - weight, liver, glucose, metabolism, blood pressure, heart, combinations - against what was actually measured, in which species, at which trial phase, and states plainly where the record simply stops.

• 2 outcomes supported by human phase 3 data
• 1 core mechanism claim with zero human measurements
• 8 absences documented with the exact searches that found nothing
• 0 published cardiovascular outcome results

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