BI 456906 (MASH)
Evidence Grade C — Moderate human evidence. 60 published studies, 38 human. 22 registered clinical trials.
This entry covers survodutide's development specifically for MASH (metabolic dysfunction-associated steatohepatitis) — a liver disease caused by fat accumulation that leads to inflammation and scarring. The same drug is listed separately for its obesity indication. The MASH programme has produced some of the strongest liver histology data of any drug in development.
60 published studies: 38 human, 0 animal, 1 in-vitro, 31 reviews
Survodutide is in Phase III development for MASH (not yet approved for this indication). The Phase II MASH trial (293 patients, 48 weeks, with liver biopsies) showed MASH improvement without worsening fibrosis in up to 62% of patients, compared to 14% with placebo. Per-protocol analysis showed up to 83% MASH improvement. Liver fat reductions of 64–67% were observed.
Phase III trials for MASH are underway. The biopsy-confirmed results from Phase II are among the strongest reported for any MASH drug candidate. See compound #160 for the obesity indication.
For the MASH indication, survodutide's glucagon receptor activation directly stimulates liver fat oxidation, reduces new fat production, and promotes fat mobilisation from liver cells. The GLP-1 component contributes weight loss and anti-inflammatory effects. This dual hepatic mechanism addresses both the root cause (excess liver fat) and the inflammatory consequence of MASH.
The Phase II MASH trial (293 patients) used liver biopsies — the gold standard for assessing liver disease — and showed MASH improvement without worsening fibrosis in up to 62% of patients, with per-protocol analysis reaching 83%. Liver fat reductions of 64-67% were observed. These results earned Breakthrough Therapy Designation from the FDA. The Phase III LIVERAGE programme (approximately 1,800 patients) began in October 2024, with a separate trial for patients with liver cirrhosis. Key uncertainties include the non-linear dose response seen in Phase II (6.0 mg was less effective than 4.8 mg), the high treatment discontinuation rate, and whether the impressive Phase II results will translate to Phase III. The MASH space is increasingly competitive, with tirzepatide, retatrutide, pemvidutide, and efinopegdutide all pursuing the same indication.
A Study in Healthy People or Otherwise Healthy With Overweight or Obesity to Compare 2 Formulations of Survodutide Given in Different Ways, Either as a Pre-filled Syringe or a Pen-like Injector
Albuminuria Reduction Study With Survodutide Treatment in Kidney Disease
A Study in People With Overweight or Obesity to Compare How 2 Different Formulations of Survodutide Are Taken up by the Body
A Study in Healthy People to Compare How 2 Different Formulations of Survodutide Are Taken up by the Body
A Study in Healthy People to Compare How 2 Different Formulations of Survodutide Are Taken up in the Body
The information on this page is provided for educational and research reference purposes only. This is not medical advice. Always consult a qualified healthcare professional before making any health-related decisions.
Exenatide was the first GLP-1 receptor agonist approved anywhere, reaching the market as Byetta in April 2005. The once-weekly formulation Bydureon followed in 2012. Clinical trials showed blood sugar reductions (HbA1c) of 1.6–1.9% and modest weight loss of 2–4 kg. The EXSCEL cardiovascular outcomes trial, involving over 14,700 patients, showed a trend toward cardiovascular benefit but narrowly missed statistical significance. While exenatide was groundbreaking as the first in its class, it has been largely overtaken by newer GLP-1 treatments that offer greater efficacy, less frequent dosing, and proven cardiovascular benefits. It remains available and in clinical use, particularly in combination products.
Lixisenatide was marketed as Adlyxin in the US (approved July 2016), though it has since been discontinued in the US market. The ELIXA cardiovascular trial, involving over 6,000 patients, was the first cardiovascular outcomes trial for any GLP-1 medication to report results. It showed a neutral cardiovascular profile — neither harmful nor beneficial — meeting safety requirements but not demonstrating the heart benefits later shown by semaglutide and liraglutide. Lixisenatide found its primary clinical role in combination with basal insulin, marketed as Soliqua (lixisenatide plus insulin glargine). This combination addresses both fasting blood sugar (via insulin) and post-meal spikes (via lixisenatide) in a single daily injection. As a standalone treatment, it has been largely superseded by more potent GLP-1 medications.
Pramlintide is marketed as Symlin (approved March 2005) and remains the only approved amylin-based treatment. It is used alongside mealtime insulin in both type 1 and type 2 diabetes. Clinical trials showed modest blood sugar improvements (HbA1c reductions of 0.2–0.6%) and approximately 2.3 kg of weight loss — less dramatic than GLP-1 treatments but meaningful as an add-on therapy. Symlin carries a boxed warning for severe hypoglycaemia, particularly when combined with insulin, and requires careful dose adjustment. Practical uptake has been limited by the need for separate injections at each meal alongside existing insulin injections. Despite its modest clinical impact, pramlintide remains the only medication that addresses the amylin deficiency in diabetes, filling a distinct biological role that GLP-1 treatments do not cover.
