Full text is available at the source.
Journal of hepatology···
Pemvidutide's effects on fatty liver disease in a controlled clinical trial
Updated
Abstract
At week 12, relative reductions in liver fat content (LFC) were 46.6%, 68.5%, and 57.1% for the pemvidutide doses of 1.2 mg, 1.8 mg, and 2.4 mg, respectively, compared to 4.4% for placebo.
- Pemvidutide treatment is associated with significant reductions in liver fat content compared to placebo.
- At the 1.8 mg dose, 94.4% of patients achieved a 30% reduction in LFC, and 55.6% achieved normalization of LFC.
- The treatment also led to a maximal weight loss of -4.3% and a decrease in alanine aminotransferase levels by -13.8 IU/L.
- Pemvidutide was well-tolerated across all doses, with no severe or serious adverse events reported.
Simplified
BACKGROUND & AIMS: This was a randomized, double-blind, placebo-controlled study to assess the effects of pemvidutide, a glucagon-like peptide-1 (GLP-1)/glucagon dual receptor agonist, on liver fat content (LFC) in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD).
METHODS: Patients with a BMI ≥28.0 kg/mand LFC ≥10% by magnetic resonance imaging-proton density fat fraction were randomized 1:1:1:1 to pemvidutide at 1.2 mg, 1.8 mg, or 2.4 mg, or placebo administered subcutaneously once weekly for 12 weeks. Participants were stratified according to a diagnosis of type 2 diabetes mellitus. The primary efficacy endpoint was relative reduction (%) from baseline in LFC after 12 weeks of treatment. 2
RESULTS: Ninety-four patients were randomized and dosed. Median baseline BMI and LFC across the study population were 36.2 kg/mand 20.6%; 29% of patients had type 2 diabetes mellitus. At week 12, relative reductions in LFC from baseline were 46.6% (95% CI -63.7 to -29.6), 68.5% (95% CI -84.4 to -52.5), and 57.1% (95% CI -76.1 to -38.1) for the pemvidutide 1.2 mg, 1.8 mg, and 2.4 mg groups, respectively, vs. 4.4% (95% CI -20.2 to 11.3) for the placebo group (p <0.001 vs. placebo, all treatment groups), with 94.4% and 72.2% of patients achieving 30% and 50% reductions in LFC and 55.6% achieving normalization (≤5% LFC) at the 1.8 mg dose. Maximal responses for weight loss (-4.3%; p <0.001), alanine aminotransferase (-13.8 IU/L; p = 0.029), and corrected cT1 (-75.9 ms; p = 0.002) were all observed at the 1.8 mg dose. Pemvidutide was well-tolerated at all doses with no severe or serious adverse events. 2
CONCLUSIONS: In patients with MASLD, weekly pemvidutide treatment yielded significant reductions in LFC, markers of hepatic inflammation, and body weight compared to placebo.
IMPACT AND IMPLICATIONS: Metabolic dysfunction-associated steatotic liver disease, and its progressive form steatohepatitis, are strongly associated with overweight/obesity and it is believed that the excess liver fat associated with obesity is an important driver of these diseases. Glucagon-like peptide-1 receptor (GLP-1R) agonists elicit weight loss through centrally and peripherally mediated effects on appetite. Unlike GLP-1R agonists, glucagon receptor agonists act directly on the liver to stimulate fatty acid oxidation and inhibit lipogenesis, potentially providing a more potent mechanism for liver fat content reduction than weight loss alone. This study demonstrated the ability of once-weekly treatment with pemvidutide, a dual GLP-1R/glucagon receptor agonist, to significantly reduce liver fat content, hepatic inflammatory activity, and body weight, suggesting that pemvidutide may be an effective treatment for both metabolic dysfunction-associated steatohepatitis and obesity.
CLINICAL TRIAL NUMBER: NCT05006885.
Related papers
Jun '23
Efinopegdutide's safety and effectiveness compared to another treatment in patients with non-alcoholic fatty liver disease
top 1% journal
cited by 174 papers
randomized controlled trial
Mar '24
Safety and effectiveness of Efruxifermin combined with a GLP-1 drug in patients with fatty liver disease and type 2 diabetes
top 2% journal
cited by 72 papers
randomized controlled trial
Sep '20
Dulaglutide's impact on liver fat in people with type 2 diabetes and fatty liver disease
top 2% journal
cited by 201 papers
randomized controlled trial
Jun '24
Changes in Liver Stiffness with Diabetes Drug Use in Fatty Liver Disease Linked to Metabolic Problems
top 50% journal
cited by 3 papers
journal article
Dec '24
Safety and effectiveness of the combined GLP-1 and FGF21 drug HEC88473 in fatty liver disease and type 2 diabetes
top 1% journal
cited by 30 papers
randomized controlled trial
Aug '18
Effects of a new drug activating both blood sugar and energy control receptors: Results from early tests in healthy people and patients
cited by 150 papers
randomized controlled trial
Oct '18
Safety and effectiveness of LY3298176, a new drug targeting two hormone receptors, in people with type 2 diabetes: a controlled phase 2 trial
top 1% journal
cited by 714 papers
randomized controlled trial
Jun '24
Using glucagon to treat metabolic diseases like type 2 diabetes and obesity
top 5% journal
cited by 30 papers
journal article
Jun '23
Retatrutide, a drug targeting three hormone receptors, for people with type 2 diabetes in a controlled US clinical trial
top 1% journal
cited by 344 papers
randomized controlled trial
Aug '24
Glucagon-like peptide 1 drugs may help treat fatty liver disease linked to metabolism problems
cited by 15 papers
editorial