# Survodutide

Boehringer's GLP-1/glucagon dual agonist: 12-13% weight loss and large liver-fat cuts in phase 3; unapproved.

- Page: https://peprank.xyz/peptides/survodutide
- Category: Metabolic & weight (Research peptide)
- Also known as: BI 456906; 'survo'
- Routes: Injection
- Safety tier: Strict: Avoid · Balanced: Caution · Evidence only: Caution
- Risk axes (0 none to 3 severe): Seen harm 1, Mechanism 3, Data gap 1, Silent harm 3, Product 3
- Positive: 56% of 24 graded reports glowing or positive, shrunk toward the 49% all-report average by 8 reports' weight
- Rank: #26 of 61 research peptides
- Graded reports: 24 (Glowing 1, Positive 13, Mixed 5, Nothing 1, Negative 3, Bad reaction 1)
- Evidence: Human RCTs — Phase 2 in obesity (n=387) and biopsy-proven MASH (n=293); phase 3 SYNCHRONIZE-1 (n=725), SYNCHRONIZE-2 (n=752) and SYNCHRONIZE-MASLD (n=216) published in 2026; cardiovascular and MASH outcome trials running; approved nowhere and no filing announced
- Access: Grey market
- Onset: Appetite effects build as the dose rises over a months-long escalation; grey-market users often feel little below about 1 mg, while some report more energy from the first dose.
- Lasts: Once-weekly injection; some users note a heart-rate bump for one to two days after each dose.
- Cost per month: ≈ €36–140 (researchers' estimate)
- Dose users report: 120–290 mcg/day (median 250 mcg, n=6)
- Updated: 2026-10-30

**Why Avoid under the strict bar:** Unapproved drug bought as grey-market vials, usually stacked on tirzepatide: the GLP-1 class's pancreatitis, gallbladder and dehydration-kidney routes, a glucagon-driven heart-rate rise whose cardiovascular safety trial is still running, and GI effects harsh enough that about one in five phase 3 participants stopped.

## What users report

Twenty-four first-hand reports: six from clinical-trial participants and the rest mostly grey-market survo added to tirzepatide ('ghetto reta'). Trial participants describe 28 kg over 20 months and 110 lb over about 15 months, but also a 3-month stall with hair thinning and one near non-responder. Stackers report stalls broken, recomposition, better liver numbers and more energy, and several say it did not raise their heart rate as retatrutide did. Complaints are GI (one quit over unrelenting diarrhoea at 2.4 mg), fatigue at higher doses, sugar cravings during the first weeks, insomnia, a 10 bpm rise for two days after each dose, and one allergic reaction with eyelid swelling. Many grey-market reports are confounded by tirzepatide. Felt nothing: 1 of 24 reports (a blinded trial participant losing about 1 lb a month) saw little; another with heavy prior GLP-1 tolerance said it 'helped a little'..

**Effects:** weight loss of 12-13% at 76 weeks in phase 3 (up to 16.6% in those who stayed on drug); liver fat cut by 30% or more in 84% vs 24% on placebo; MASH improvement in up to 62% vs 14%; visceral-fat, triglyceride and blood-pressure reductions; appetite and food-noise suppression, often with more energy

**Downsides:** GI effects in 81-90% in phase 3 (vs 48% on placebo), leading 18-20% to stop; fatigue, especially at higher doses; sugar cravings for the first weeks; constipation or diarrhoea; insomnia and a higher resting heart rate in some users

**Risks:** Pancreatitis, gallbladder disease and dehydration-related kidney injury: GLP-1 class harms with label warnings on approved agonists; Heart-rate rise from glucagon-receptor agonism; a dedicated cardiovascular outcomes trial (SYNCHRONIZE-CVOT) has not reported; Thyroid C-cell tumours in rodents for the GLP-1 agonist class (boxed warning on semaglutide, tirzepatide and mazdutide); Stacking on tirzepatide adds a second GLP-1 agonist in a combination never trialled; Grey-market vials of unknown dose, purity and sterility

**Caveat:** SYNCHRONIZE-1's placebo group lost 5.4%, partly because about 15% of them obtained GLP-1 drugs outside the trial, and a rigid dose escalation may have inflated GI dropouts, so the true effect and tolerability sit somewhere between the headline numbers. Users' belief that survodutide does not raise heart rate rests on anecdote; the glucagon arm raises it in the class.

**Typical use:** Trials: slow weekly escalation (20-24 weeks in phase 2) to 3.6 mg or 6.0 mg in phase 3 (phase 2 tested 0.6-4.8 mg). Grey-market users: start 0.2-0.3 mg, usually 1-2.5 mg weekly beside tirzepatide.

**Getting it:** Unapproved; obtainable legitimately only in clinical trials. Grey-market vials (mostly 10 mg) are bought for tirzepatide stacks, often via Telegram groups.

**Stacked with:** tirzepatide (The 'ghetto reta' stack adding glucagon agonism; the dominant grey-market use, never trialled.); cagrilintide (Occasionally added for appetite, or kept on when switching from retatrutide.); retatrutide (Not combined; users switch to survodutide when retatrutide raises their heart rate or causes anxiety.)

## Risk profile

- **Seen harm 1/3:** No label, no published case reports and no deaths across about 2,400 phase 2-3 participants. Serious adverse events were not raised in phase 2 (4% vs 7% in obesity, 8% vs 7% in MASH). The striking signal is GI discontinuation (18-20% vs 3% in SYNCHRONIZE-1), which is not serious harm by the rubric. Reddit adds one anecdotal allergic reaction with eyelid swelling that needed medication.
- **Mechanism 3/3:** As a GLP-1 receptor agonist it belongs to a class shown in vivo to cause acute pancreatitis and gallbladder disease in humans and thyroid C-cell tumours in rodents (label warnings on semaglutide, tirzepatide and the sister dual agonist mazdutide); survodutide's own rodent carcinogenicity data are not public. Its glucagon arm raises heart rate, and Boehringer is running a dedicated cardiovascular outcomes trial because the cardiovascular effects of dual glucagon/GLP-1 agonism are unknown.
- **Data gap 1/3:** Not approved anywhere and no filing announced, but controlled trials have now put well over a thousand people on survodutide for up to 76 weeks (phase 3 SYNCHRONIZE-1, -2 and -MASLD; phase 2 obesity and MASH). Cardiovascular and liver-outcome trials are still running, and nothing covers it stacked on tirzepatide.
- **Silent harm 3/3:** The mechanism axis points at the GLP-1 class's thyroid C-cell tumour concern, a theoretical tumour pathway that the rubric scores 3; the heart-rate rise is also silent without a monitor. Pancreatitis, cholecystitis, dehydration and GI effects would be noticed quickly.
- **Product 3/3:** Outside trials the only source is grey-market injectable vials, usually 10 mg, reconstituted at home and dosed by the vendor's label claim; users discuss buying through Telegram groups.
- **Never if:** Personal or family history of medullary thyroid carcinoma or MEN 2 (GLP-1 class); Pregnancy, planned pregnancy or breastfeeding; History of pancreatitis or gallbladder disease; Gastroparesis or severe GI disease; Uncontrolled hypertension, recent cardiovascular event or tachyarrhythmia (excluded from SYNCHRONIZE-1); Poorly controlled mood disorder (excluded from SYNCHRONIZE-1); Under 18

## Top reports

- Glowing, metabolic: “I have lost 110 pounds on Survodutide. It’s works great. I started April 2024 at 307 and now weigh 197. I’m in a trial for people with kidney and cardiovascular disease.” — [r/survodutide](https://www.reddit.com/r/survodutide/comments/1lzm0l7/survotirz_stack_starting_today/n3vmeoa/)
- Positive, metabolic, 0.3 mg rising to 0.6 mg/week: “Yesterday had noticeable energy increase. Today a slight increase. Less hungry than I if I was just on tirz.” — [r/survodutide](https://www.reddit.com/r/survodutide/comments/1mfhdgu/started_survo_yesterday/)
- Positive, metabolic: “I was on a trial for the last 20 months. I lost 28kg/62lbs in that time. I didn’t do any other GLPs in that time” — [r/survodutide](https://www.reddit.com/r/survodutide/comments/1r2huv3/has_anyone_here_done_survo_without_stacking_other/o4xd4cg/)
- Positive, metabolic: “Im on survo. I love it. Great appetite suppression..mild constipation and it doesn't increase my resting heart rate.” — [r/survodutide](https://www.reddit.com/r/survodutide/comments/1ldp3h3/survo_vs_rettirz/myb1fzh/)
- Positive, metabolic, 3.6 mg/week: “Been on it for 3 months dose of 3.6 no vision changes, only other one I’ve taken was semaglutide alone. The food noise decrease is much better with survo” — [r/survodutide](https://www.reddit.com/r/survodutide/comments/1mfhdgu/started_survo_yesterday/n6if217/)

## Studies

- [le Roux et al. 2026: SYNCHRONIZE-1, survodutide once weekly for adults with obesity (NEJM)](https://pubmed.ncbi.nlm.nih.gov/42253238/) (rct, n=725, 2026): At 76 weeks weight fell 12.2% (3.6 mg) and 13.0% (6.0 mg) vs 5.4% on placebo; GI effects in 81-90% vs 48%, and 18-20% stopped for GI effects vs 3%.
- [Wharton et al. 2026: SYNCHRONIZE-2, survodutide in adults with obesity and type 2 diabetes (NEJM)](https://pubmed.ncbi.nlm.nih.gov/42820639/) (rct, n=752, 2026): In type 2 diabetes weight fell 8.2% and 9.8% vs 3.9% on placebo at 76 weeks, with HbA1c down about 0.9 points.
- [SYNCHRONIZE-MASLD 2026: survodutide in obesity with at-risk fatty liver disease (Nature Medicine)](https://pubmed.ncbi.nlm.nih.gov/42252333/) (rct, n=216, 2026): After 48 weeks on 6 mg, 84% vs 24% on placebo cut liver fat by at least 30%, and weight fell 12.2% vs 1.0%.
- [Sanyal et al. 2024: phase 2 trial of survodutide in MASH and fibrosis (NEJM)](https://pubmed.ncbi.nlm.nih.gov/38847460/) (rct, n=293, 2024): On biopsy, MASH improved without fibrosis worsening in 47-62% vs 14% on placebo over 48 weeks; nausea 66%, diarrhoea 49% and vomiting 41%, with serious adverse events 8% vs 7%.
- [le Roux et al. 2024: dose-finding phase 2 trial of survodutide for obesity (Lancet Diabetes Endocrinol)](https://pubmed.ncbi.nlm.nih.gov/38330987/) (rct, n=387, 2024): Weight fell 6.2-14.9% vs 2.8% on placebo at 46 weeks, but 25% on survodutide stopped for adverse events (mostly GI) vs 4% on placebo.

## Sources

- [le Roux et al. 2026, SYNCHRONIZE-1 (NEJM)](https://www.nejm.org/doi/full/10.1056/NEJMoa2600751)
- [Sanyal et al. 2024, survodutide phase 2 in MASH (NEJM)](https://doi.org/10.1056/NEJMoa2401755)
- [SYNCHRONIZE-CVOT rationale and design (JACC Heart Failure 2024)](https://pubmed.ncbi.nlm.nih.gov/39453356/)
- [pharmaphorum: ADA 2026, survodutide GI dropout 19% vs 2.9%; no filing plans announced](https://pharmaphorum.com/news/ada-safety-data-offset-efficacy-survodutide)
- [Boehringer Ingelheim: SYNCHRONIZE-1 topline, 16.6% weight loss (efficacy estimand)](https://www.newswire.ca/fr/news-releases/boehringer-ingelheim-s-novel-glucagon-glp-1-dual-agonist-survodutide-achieved-significant-weight-loss-of-16-6-delivering-meaningful-metabolic-improvement-in-people-with-obesity-or-overweight-in-phase-iii-trial-860299396.html)
- [FDA: concerns with unapproved GLP-1 drugs used for weight loss](https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss)