Dual GLP-1/GIP agonist shows promising impact on liver fat, lipids on top of weight loss
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Key takeaways:
- An investigational GLP-1/GIP dual agonist induced up to 7.8% weight loss at 28 days in a phase 1 study.
- Reductions in liver fat were observed for adults with NAFLD.
DALLAS — New data presented at ObesityWeek demonstrate an encouraging early profile of an investigational dual GLP-1/GIP receptor agonist in healthy adults, according to a speaker at ObesityWeek.
VK2735 (Viking Therapeutics) is a novel dual agonist of the GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors in development for the potential treatment of various metabolic disorders such as obesity.
Joel Neutel, MD, FASH, director of research at the Orange County Heart Institute and Research Center in Tustin, California, presented the first-in-human, phase 1, randomized, double-blind, placebo-controlled single- and multiple-dose study of VK2735 in healthy adults. The single-dose portion of the study evaluated treatment in healthy adults; the multiple-dose portion included healthy adults with a minimum BMI of 30 kg/m2. The study objections were to evaluate safety and tolerability of single and multiple doses of subcutaneous VK2735 and to identify suitable doses for further clinical development, according to a company press release.
“You can see in this phase 1 study looking at a dual agonist a very encouraging early profile observed in healthy subjects with a BMI of greater than 30 kg/m2,” Neutel said during the presentation. “We saw dose-dependent improvements in weight of up to 7.8% in a small amounts of patients after just 28 days. Durable weight loss was maintained 21 days after dosing. We saw a rapid effect on liver fat, suggestion a potential benefit in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) patients.”
In the multiple-ascending dose portion of the study, the researchers observed reductions in mean body weight from baseline ranging up to 7.8% and reductions compared with placebo ranging up to 6% at 28 days. Significant differences in weight change with VK2735 compared with placebo were maintained or improved at 43 days of follow-up.
Potential benefits on liver fat, lipids
At 28 days, liver fat content was also reduced, with reductions ranging up to 47.3% from baseline. In a subgroup of participants with NAFLD, liver fat reductions were even more pronounced, with reductions from baseline after 4 weekly doses of up to 49.7%, and up to 58.5% compared with placebo.
“When you look at the very impressive and significant reductions in liver fat after only 28 days in these subjects, it clearly suggests longer treatment could provide benefits in NAFLD and NASH,” Neutel said.
The study also evaluated change in 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). Reductions in lipid levels were observed after four weekly doses. The researchers reported dose-dependent effects across all cohorts. There were no changes in levels of HDL cholesterol.
Mot adverse events mild
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%), including GI-related adverse events. Nausea was the most common GI-related adverse event reported, with 89% of those reports being mild and 11% moderate. Neutel said no consistent dose relationship was observed for the GI-related adverse events and there were no discontinuations related to GI-related adverse events.
There were two severe adverse was reported; one was acute choledocholithiasis requiring surgery and the other being infectious mononucleosis. No hypoglycemia was reported.
Viking Therapeutics said it plans to build upon these phase 1 data with its ongoing phase 2 VENTURE study, which is evaluating safety and efficacy of VK2735 in patients with obesity over 13 weeks of treatment, according to the release.
Reference:
Viking Therapeutics presents new data from phase 1 clinical trial of dual GLP-1/GIP receptor agonist VK2735 in oral presentation at ObesityWeek 2023. Available at https://www.prnewswire.com/news-releases/viking-therapeutics-presents-new-data-from-phase-1-clinical-trial-of-dual-glp-1gip-receptor-agonist-vk2735-in-oral-presentation-at-obesityweek-2023-301959191.html. Published Oct. 17, 2023. Accessed Oct. 18, 2023.
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Neutel J, et al. Oral-089. Presented at: ObesityWeek; Oct. 14-17, 2023; Dallas.
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