Survo

Survo is a 29-amino-acid synthetic analogue of glucagon designed for simultaneous engagement of both the GLP-1 receptor (GLP-1R) and glucagon receptor (GCGR). Structural work describes a backbone incorporating substitutions from GLP-1 and exendin peptides, along with the non-natural amino acid Ac4c (1-aminocyclobutane-1-carboxylic acid) at position 2. The Lys-24 side chain is acylated with an 18-carbon dicarboxylic acid, extending plasma half-life through reversible albumin binding — a strategy also used across other long-acting acylated peptides in this class. Thomas et al. (2024) profiled Survo in vitro alongside related dual agonist peptides, measuring intracellular cAMP production in cells expressing human GLP-1R and GCGR, as well as in rodent islet cell preparations. This work characterized the compound's receptor engagement at both targets using standard cAMP reporter assays and places Survo within the class of long-acting dual class B GPCR agonists.

Thomas et al. (2024) included rodent islet preparations to assess insulinotropic activity in vitro and characterized the pharmacological properties of Survo and related analogues in cell-based systems. Pharmacokinetic studies in animal models demonstrated that Survo's acylation strategy supports extended plasma exposure, consistent with other fatty-acid-linked peptides in this class. Preclinical pharmacology literature for this class of dual agonists has additionally described rodent models of metabolic dysfunction, though Survo's own preclinical data have been reported primarily alongside clinical-stage investigations.

Le Roux et al. (2024) reported a phase 2, randomized, placebo-controlled trial examining multiple once-weekly dose levels of Survo in a metabolic clinical research population, over 46 weeks. Primary endpoints included metabolic endpoints, with pharmacodynamic assessments of heart rate and glycemic parameters also included. The safety assessment protocol monitored gastrointestinal events consistent with GLP-1 receptor pharmacology. The trial examined these endpoints across a dose range, characterizing Survo's pharmacological profile in a metabolic clinical research setting.

Sanyal et al. (2024, N Engl J Med) reported a phase 2, placebo-controlled trial in adults with biopsy-confirmed metabolic-associated steatohepatitis (MASH) with liver fibrosis, examining Survo over 48 weeks. The trial's primary endpoints included liver histology assessment and MRI-PDFF measurement of hepatic fat content. The study design focused on whether combined GLP-1 and glucagon receptor engagement could be evaluated through histological and imaging endpoints in a MASH population. Glucagon receptor signaling is studied in the context of hepatic lipid metabolism, making dual GLP-1/GCGR agonism a pharmacological area of interest in steatohepatitis research.

Sanyal et al. (2024, J Hepatol) reported a phase 1 study (NCT05296733) examining the pharmacokinetics of Survo in subjects with compensated and decompensated liver cirrhosis, compared with matched healthy volunteers. Single and multiple dose levels were administered, with standard pharmacokinetic parameters (Cmax, AUC) measured across populations. Exploratory assessments included noninvasive liver measurements — MRI-based hepatic fat and stiffness — over 28 weeks. The study characterized whether hepatic impairment alters Survo's exposure profile relative to subjects with normal liver function.