GLP-1/GIP dual agonists show favorable effects on liver fat and blood lipids beyond weight loss

October 18, 2023

2 min read


We are unable to process your request. Please try again later. If you are still experiencing this issue, please contact customerservice@slackinc.com.

Key points:

  • In a Phase 1 study, the investigational GLP-1/GIP dual agonist resulted in weight loss of up to 7.8% at 28 days.
  • Reduced liver fat was observed in adults with NAFLD.

DALLAS — New data published at ObesityWeek show encouraging early performance in healthy adults for an investigational dual GLP-1/GIP receptor agonist, a spokesperson said.

VK2735 (Viking Therapeutics) is a novel dual agonist of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors, which is under development and can be used to treat various metabolic diseases such as obesity.



Key takeaways from the VK2735 Phase 1 trial
Data from Neutel J et al. Oral-089. Posted in: Obesity Week; October 14-17, 2023; Dallas.

Joel Neutel, MD, FASH, Research Director, Orange County Heart Institute and Research Center, Tustin, CA First-in-human, Phase 1, randomized, double-blind, placebo-controlled single-dose and multiple-dose studies of VK2735 in healthy adults are described. The single-dose portion of the study evaluated treatment in healthy adults; the multiple-dose portion included healthy adults with a BMI as low as 30 kg/m2. The purpose of the study is to evaluate the safety and tolerability of single and multiple subcutaneous doses of VK2735 and to determine appropriate doses for further clinical development, according to a company press release.

You can see the very encouraging early characteristics observed in healthy subjects with a BMI greater than 30 kg/m2 in this Phase 1 study of dual agonists2“After only 28 days, we found a dose-dependent improvement in body weight in a small number of patients, up to 7.8%,” Neutel said in his presentation. Sustained weight loss for 21 days post-dose. “We saw rapid effects on liver fat, suggesting potential benefit for patients with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).”

In the multiple ascending dose portion of the study, researchers observed a 7.8% reduction in mean body weight from baseline at 28 days and a 6% reduction compared with placebo. Compared with placebo, body weight changes with VK2735 were maintained or improved over 43 days of follow-up.

Potential benefits for liver fat and blood lipids

On day 28, liver fat content also decreased, with a reduction of up to 47.3% compared to baseline. Liver fat reduction was more pronounced in the subgroup of participants with NAFLD, with up to 49.7% reduction in liver fat after 4 weeks of weekly dosing and up to 58.5% reduction in liver fat compared to placebo.

“These subjects experienced an impressive and significant reduction in liver fat after just 28 days, clearly demonstrating that longer treatment can provide benefits for NAFLD and NASH,” Neutel said.

The study also evaluated changes in blood lipid levels after 28 days of treatment, including apolipoprotein B (up to 20.5% change from baseline), LDL cholesterol (up to 23% change from baseline), and total cholesterol (up to 21% change from baseline) . Reductions in blood lipid levels were observed after taking the drug four times per week. The researchers reported dose-dependent effects across all cohorts. HDL cholesterol levels did not change.

Mot adverse events were minor

Neutel also highlighted previously reported safety and tolerability results from the Phase 1 trial. VK2735 was well tolerated in the multiple-dose portion of the study. Adverse events observed during the study were mild (80%) or moderate (18%) and included gastrointestinal-related adverse events. Nausea was the most common gastrointestinal-related adverse event, with 89% being mild and 11% being moderate. No consistent dose relationship was observed for gastrointestinal-related adverse events, and there were no discontinuations due to gastrointestinal-related adverse events, Neutel said.

Two serious adverse events were reported; one was acute choledocholithiasis requiring surgery and the other was infectious mononucleosis. There were no reports of hypoglycemia.

Viking Therapeutics said it plans to build on these Phase 1 data with its ongoing Phase 2 VENTURE study, which is evaluating the safety and efficacy of VK2735 in obese patients for 13 weeks.

refer to:

Viking Therapeutics presented new data from a Phase 1 clinical trial of the dual GLP-1/GIP receptor agonist VK2735 in an oral presentation at ObesityWeek 2023. Available at https://www.prnewswire.com/news-releases/viking-therapeutics-presents-new-bi-glp-1gip-agonist-vk2735-in-oral-presentation-at-obesityweek-2023-301959191 .html Phase 1 clinical trial data. Release date: October 17, 2023. Accessed: October 18, 2023.

Source/Disclosure

collapse

source:

Neutel J et al. Oral-089. Posted in: Obesity Week; October 14-17, 2023; Dallas.


Disclosure: Neutel reports consulting services for E Star Pharmaceuticals, Oramed Pharmaceuticals and Viking Therapeutics.

Source link

Leave a Comment