Survodutide

Survodutide is a synthetic peptide derived from the human glucagon sequence, modified to also activate the GLP-1 receptor. It is composed of 29 amino acids and includes a non-standard residue (Ac4c) and a C18 fatty-acid chain attached via a linker to prolong its action.

Survodutide’s dual activation of the glucagon receptor (GCGR) and the GLP-1 receptor (GLP-1R) is thought to offer metabolic benefits: it may reduce appetite, boost insulin secretion, increase energy expenditure, and promote fat metabolism

Survodutide is a dual agonist that activates both glucagon and GLP‑1 receptors, and this gives it clear metabolic advantages. In a phase 2 obesity trial, once‑weekly injections of survodutide produced up to ~14.9 % mean weight loss at 46 weeks, with higher doses leading to greater reductions in body mass ¹. A meta‑analysis of randomized controlled trials confirmed that it significantly lowers body weight, BMI, and waist circumference, especially at higher doses and over longer treatment periods ². Preclinical animal studies show that its effectiveness comes from not only reducing food intake but also increasing energy expenditure via glucagon receptor activation ³.

Beyond weight loss, survodutide appears to improve liver health in people with metabolic dysfunction‑associated steatohepatitis (MASH). In a 48‑week phase 2 trial of patients with biopsy‑confirmed MASH and fibrosis (F1–F3), survodutide substantially improved MASH without worsening fibrosis; in the 4.8 mg dose group, 62 % had histologic improvement compared to 14 % with placebo ⁴. The same study showed that up to 67 % of treated patients saw at least a 30 % reduction in liver fat and that 36 % achieved at least one‑stage improvement in fibrosis ⁵. Thus, survodutide offers both strong weight‑reduction benefits and meaningful therapeutic effects on liver fat and fibrosis.

Survodutide’s most common and troubling side effects in clinical trials are gastrointestinal. In a 16‑week Phase II trial in people with type 2 diabetes, 77.8 % of survodutide-treated participants reported at least one adverse event, and 55.3 % of them were GI disorders such as nausea, vomiting, diarrhea, or dyspepsia ⁶. Serious adverse events occurred in 3.6 % of patients, and 15.9 % discontinued treatment, mostly during the rapid dose–escalation phase, with GI issues being the primary reason ⁷.

In a longer 46‑week Phase II obesity trial, up to 91 % of participants on survodutide experienced adverse events, and 75 % of those were GI-related (nausea, vomiting, diarrhea, constipation). About 24.6 % of participants stopped treatment due to these side effects, especially early on when doses were being increased quickly ^{9, 10}. In conclusion, while survodutide shows promise for weight loss and glycemic control, its high rate of gastrointestinal side effects—especially during the early, rapid escalation of dose—represents a major tolerability challenge in clinical use.

Survodutide is a balanced dual agonist for the glucagon receptor (GCGR) and the GLP‑1 receptor (GLP‑1R), allowing it to engage both pathways simultaneously. Preclinical rodent studies showed it increased cyclic AMP signaling through both receptors, leading to weight loss by reducing food intake via GLP‑1R and enhancing energy expenditure through GCGR-mediated lipolysis and gluconeogenesis ⁸. Human clinical trials in individuals with obesity or type 2 diabetes confirmed target engagement, showing changes in amino acids and glucagon levels consistent with GCGR activation, along with reductions in HbA1c reflecting GLP‑1R activation. Phase 2 studies demonstrated significant weight loss, reduced waist circumference, and lower triglycerides, highlighting its integrated metabolic effects ^{9, 10}. Overall, Survodutide exerts coordinated metabolic control by simultaneously modulating appetite, energy expenditure, and glucose metabolism.

Survodutide (BI 456906) is currently in clinical development in the United States — it has not yet received FDA approval for general use, though it was granted Breakthrough Therapy status for treatment of non‑cirrhotic metabolic dysfunction–associated steatohepatitis (MASH) and is being evaluated in Phase III trials ¹¹. For athletes, Survodutide is not explicitly listed on the World Anti-Doping Agency's (WADA) current prohibited substances list because it is still an investigational drug in clinical trials and not yet approved for general use. However, if it receives regulatory approval in the future, it will almost certainly be classified as a prohibited substance in sports.