Survodutide: Novel GCGR/GLP-1RA Shows Promise in Obesity, MASH Treatment

New data presented at the 60th Annual Meeting of the European Association for the Study of Diabetes (EASD) 2024 showed survodutide (Boehringer Ingelheim) may be beneficial for individuals with obesity or overweight and metabolic dysfunction-associated steatohepatitis (MASH).

The findings from two phase 2 clinical trials were presented during a symposium on multiagonist therapy for the treatment of diabetes and obesity.

Study #1: Efficacy of survodutide in persons with overweight/obesity

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The first study (NCT04667377) examined the efficacy of the novel glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R) dual agonist in 387 persons aged 18 to 75 years with overweight or obesity without type 2 diabetes (T2D). Participants were randomly assigned to receive placebo or 1 of 5 doses of survodutide once-weekly: 0.6 mg, 2.4 mg, 3.6 mg, or 4.8 mg.

Results showed that survodutide was associated with up to an 18.7% dose-dependent reduction in body weight over 46 weeks compared with placebo. “What is very interesting to see here is that at the higher doses, we have not yet achieved a plateau, suggesting that with longer treatment duration an even greater body weight loss is conceivable,” presenter Anton Pekcec, MD, head of diabetes and obesity research at Boehringer Ingelheim in Germany said during his review of the data.

Moreover, up to 40% of participants who received survodutide achieved a body weight reduction of 20% or more after 46 weeks of treatment. Pekcec also stated that survodutide treatment reduced absolute systolic and diastolic blood pressure up to 8.6 mm Hg and 4.8 mm Hg over the treatment period.

In addition, survodutide had an acceptable safety profile, and most adverse events (AEs) were gastrointestinal-related which is expected with GLP-1RAs. According to Pekcec, most treatment discontinuation due to AEs that occurred were caused by the rapid dose-escalation phase and may be mitigated with more gradual dose-escalation.

Study #2: Survodutide in persons with MASH

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The second study (NCT04771273) assessed survodutide in 295 adults with MASH who were randomly assigned to receive placebo or 1 of 3 doses of survodutide (2.4 mg, 4.8 mg, or 6 mg). The phase 2 study’s primary endpoint was histologic improvement of MASH without worsening of fibrosis after 48 weeks of treatment, defined as a reduction of ≥2 points in non-alcoholic fatty liver disease activity score (NAS) with ≥1 point decrease in lobular inflammation or ballooning subscores.

According to Pekcec, the primary endpoint was met, with up to 83% of survodutide-treated participants showing improvement in MASH with no worsening in fibrosis. Also, one of the key secondary endpoints—decrease in liver fat content (LFC) of 30% or more from baseline—was met, with up to 87% of survodutide-treated individuals reaching improvement in LFC.

Pekcec noted at the end of his presentation that survodutide is currently being investigated in a phase 3 clinical trial program among patients with obesity.

Reference: Pekcec A. Survodutide: A novel GCGR/GLP-1R dual agonist in development for people living with overweight/ obesity and MASH. Presented at EASD 2024; September 10-13, 2024. Madrid, Spain.