Survodutide Research & Studies

Although medications with glucagon-like peptide-1 (GLP-1) receptor agonist activity have transformed the management of obesity and shown substantial cardiometabolic benefits, unmet needs remain. Survodutide, an investigational glucagon receptor-GLP-1 receptor dual agonist, led to substantial weight reduction in a phase 2 trial involving adults with obesity without diabetes.

Survodutide, a novel glucagon receptor and glucagon-like peptide-1 (GLP-1) receptor dual agonist, elicited significant weight loss in a phase 2 trial in individuals with obesity without type 2 diabetes (T2D). Two multinational phase 3 trials are investigating survodutide for obesity management in individuals with or without T2D. We report the baseline characteristics of participants in the SYNCHRONIZE-1 trial in adults with obesity without T2D (ClinicalTrials.gov: NCT06066515).

Survodutide is an investigational glucagon receptor/glucagon-like peptide-1 receptor dual agonist that has shown promise for treating obesity and its complications in Phase 2 trials. Two double-blind, randomized, global Phase 3 trials are designed to assess the efficacy and safety of survodutide for treatment of obesity-SYNCHRONIZE™-1 in people with obesity without type 2 diabetes (T2D) and SYNCHRONIZE™-2 in people with obesity and T2D. This paper describes the baseline characteristics of participants in SYNCHRONIZE-2 (ClinicalTrials.gov identifier NCT06066528).

This post hoc analysis evaluated the effect of survodutide on beta-cell function, insulin sensitivity, and glucose biomarkers in two phase 2 trial populations.

Survodutide is a novel GCG/GLP-1 receptor (GCGR/GLP-1R) dual agonist in clinical development for people with obesity and people with metabolic dysfunction-associated steatohepatitis (MASH). Preclinically, survodutide demonstrated body weight lowering efficacy through decreased energy intake and increased energy expenditure. Here, we investigated the central site of action of survodutide and provide further insights into its mechanism of action in reducing body weight. We assessed GCGR and GLP1R expression in human and mouse circumventricular organs (CVOS) and showed for the first time that GCGR is barely detectable in area postrema (AP) and arcuate nucleus of the hypothalamus (ARH) at the single cell level. In contrast, GLP1R is expressed in these tissues. Using a fluorophore labeled survodutide to visualize sites of action in the mouse brain, survodutide was observed to directly access the CVOs and adjacent hypothalamic and hindbrain nuclei, without evidence of uniformly crossing the blood-brain-barrier. In addition, c-Fos labeling showed that multiple nuclei associated with the control of food intake were activated by survodutide. Consistent with the hypothesis that the intake suppressive effects of survodutide are GLP-1R dependent, a long-acting GCGR agonist did not induce neuronal activation in satiety-mediating regions, nor reduced food intake but showed reduction in body weight. These data further support the dual mode of action of survodutide and its potential to provide clinical benefit for people with obesity and/or MASH.

There is an unmet need for effective pharmacotherapy for obesity disease management in Japan. Survodutide is a novel glucagon receptor/glucagon-like peptide-1 receptor (GLP-1R) dual agonist with the potential to induce greater weight reductions than GLP-1R mono-agonists. We report the design and baseline participant characteristics of the SYNCHRONIZE-JP trial evaluating survodutide in Japanese adults with obesity disease (ClinicalTrials.gov: NCT06176365).

Survodutide represents an innovative approach to obesity management and metabolic-associated fatty liver disease (MAFLD). These conditions, often closely linked with type 2 diabetes (T2DM) and cardiovascular diseases, demand effective treatment strategies. Survodutide acts by targeting both GLP-1 and glucagon receptors. This new dual agonist offers potential transformative benefits, with early clinical trials showcasing significant weight loss and improvements in metabolic markers. Survodutide's mechanism of action includes appetite regulation, enhanced glucose metabolism, and increased energy expenditure, making it a promising option for those struggling with obesity and related health issues. This review assesses Survodutide's pharmacology, efficacy, and safety in MASH and obesity, while also outlining its broader metabolic and cardiovascular benefits. It compares Survodutide's dual-agonist mechanism and clinical performance with single-target incretin therapies to clarify its potential role in the evolving treatment landscape. While the initial results are promising, the review emphasizes the importance of continued research to fully understand Survodutide's long-term safety and effectiveness. Ongoing trials will provide critical insights into its overall impact, side effects, patient response, and cost considerations. This article highlights Survodutide's potential in the treatment of obesity and metabolic disordersand evaluates its place in therapy for seeking improved outcomes.

Survodutide was associated with improvements in liver-related endpoints in a phase 2 trial in MASH (NCT04771273). This post hoc mediation analysis evaluated the proportion of the direct treatment effect versus the indirect effect mediated by weight reduction.

Cardiovascular disease remains the leading cause of mortality worldwide, with obesity, type 2 diabetes, and metabolic dysfunction-associated steatohepatitis (MASH) serving as major upstream drivers. Current therapies largely address downstream risk factors, leaving a need for agents that modify the metabolic contributors to cardiovascular disease. Survodutide, a dual glucagon and glucagon-like peptide-1 receptor agonist, represents an emerging therapy with broad metabolic effects, including potent weight reduction, glycemic control, hepatic fat reduction, and anti-inflammatory activity. Phase 2 trials have demonstrated weight loss up to 18.7% and HbA1c reductions up to -1.71%, outperforming semaglutide for weight outcomes while maintaining comparable glycemic efficacy. In MASH, survodutide achieved significant improvements in liver fat and fibrosis, offering potential cardiovascular protection through reductions in systemic inflammation and fibrosis-related remodeling. Its mechanistic profile suggests benefits for visceral and epicardial adiposity, with implications for heart failure with preserved ejection fraction. Early signals of renal benefit further underscore its role in cardiorenal syndromes. Adverse events, primarily gastrointestinal intolerance and modest heart rate increases, remain important limitations, contributing to discontinuation rates higher than comparator agents. The ongoing Survodutide for the treatment of obesity study (SYNCHRONIZE-CVOT) trial will clarify whether these robust metabolic effects translate into reduced cardiovascular events and long-term safety. Survodutide has the potential to reshape cardiometabolic care by addressing multiple converging pathways that drive cardiovascular disease. Confirmation of its safety and efficacy in outcomes trials could establish dual agonism as a cornerstone therapeutic strategy for patients with obesity, type 2 diabetes, MASH, and cardiorenal disease.

This meta-analysis aimed to evaluate the efficacy and safety of survodutide on glycemic control and weight loss in adults.

The objective of this study was to describe the rationale and design of two multinational phase 3 clinical trials of survodutide, an investigational glucagon and glucagon-like peptide-1 receptor dual agonist for the treatment of obesity with or without type 2 diabetes (T2D; SYNCHRONIZE-1 and -2).

Dual agonism of glucagon receptor and glucagon-like peptide-1 (GLP-1) receptor may be more effective than GLP-1 receptor agonism alone for treating metabolic dysfunction-associated steatohepatitis (MASH). The efficacy and safety of survodutide (a dual agonist of glucagon receptor and GLP-1 receptor) in persons with MASH and liver fibrosis are unclear.

Obesity is a widespread and chronic condition that requires long-term management; research into additional targets to improve treatment outcomes remains a priority. This study aimed to investigate the safety, tolerability, and efficacy of glucagon receptor-GLP-1 receptor dual agonist survodutide (BI 456906) in obesity management.

Glucagon-like peptide-1 receptor (GLP-1 R) agonists have demonstrated remarkable effectiveness in the treatment of obesity and type 2 diabetes. Although these agents provide beneficial effects for metabolic dysfunction-associated steatohepatitis (MASH) through their glucose-lowering and weight-reducing properties, their efficacy in promoting fibrosis regression remains unproven. Survodutide, an investigational dual agonist that simultaneously targets both the glucagon receptor (GCGR) and GLP-1 R, has emerged as a promising therapeutic candidate for the comprehensive management of obesity and MASH. By engaging these two critical receptors, this drug has the potential to offer a broad spectrum of metabolic benefits, addressing multiple pathogenic mechanisms underlying these interrelated disorders.

To describe the biomarker strategy that was applied to select survodutide (BI 456906), BI 456908 and BI 456897 from 19 dual glucagon receptor (GCGR)/ glucagon-like peptide-1 receptor (GLP-1R) agonists for in-depth pharmacological profiling, which led to the qualification of survodutide as the clinical development candidate.

ClinicalTrials.gov NCT04153929 and EudraCT 2019-002390-60.

Survodutide is a glucagon/glucagon-like peptide-1 receptor dual agonist in development for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). We investigated the pharmacokinetic and safety profile of survodutide in people with cirrhosis.