Oral GLP-1/GIP Dual Agonist VK2735 Achieves Up to 12% Weight Loss in Phase II VENTURE Trial

Author(s):

Key Takeaways

VK2735 achieved significant weight reduction, with up to 12.2% mean body weight loss from baseline over 13 weeks.
The trial's exploratory cohort showed effective weight maintenance with a down-titration strategy from 90 mg to 30 mg.
Safety and tolerability were encouraging, though VK2735 had a higher discontinuation rate due to adverse events compared to placebo.
Viking plans to advance VK2735 into Phase III trials, focusing on obesity and type 2 diabetes in the VANQUISH program.

The Phase II VENTURE-Oral Dosing study of VK2735 met primary and secondary endpoints, with once-daily treatment leading to progressive weight reductions, high responder rates, and encouraging safety over 13 weeks.

Credit: Key design | stock.adobe.com

What clinops professionals need to know

The Phase II VENTURE-Oral Dosing trial of VK2735 met primary and secondary endpoints, showing up to 12.2% mean weight loss at 13 weeks with strong dose response. An exploratory cohort maintained reductions after down-titration, supporting a potential maintenance strategy. VK2735 was generally well tolerated, and Phase III trials are underway.

Viking Therapeutics has shared new data from its Phase II VENTURE-Oral Dosing trial (NCT06828055) of VK2735, a dual agonist of the glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. The trial met both its primary and secondary endpoints with VK2735 demonstrating statistically significant reductions in body weight compared with placebo.¹

Significant weight reductions achieved with VK2735

More detailed results from this readout of the VENTURE-Oral Dosing study show:

Once-daily oral VK2735 produced statistically significant mean body weight reductions of up to 12.2% from baseline at 13 weeks.
Compared to placebo, VK2735 achieved statistically significant relative weight reductions of up to 10.9%.
Weight loss was progressive across all doses with no plateau observed at 13 weeks.
Statistically significant differences versus baseline and placebo were observed for all doses above 15 mg starting at week 1 and sustained through week 13.
On the key secondary endpoint, up to 97% of VK2735-treated participants achieved at least 5% weight loss, compared to 10% on placebo.
Up to 80% of VK2735-treated participants achieved at least 10% weight loss, compared to 5% on placebo.

In a press release, Brian Lian, PhD, chief executive officer of Viking, said: "We are excited to report the top-line Phase II study results for the once-daily oral tablet of VK2735. As in prior studies we observed a clear dose response and impressive weight loss across the 13-week treatment period. The progressive nature of the weight loss curves suggests the potential for further improvement with longer dosing periods. The experimental maintenance arm of this study provides an encouraging signal that supports our belief that transitioning patients from higher doses, injectable or oral, to low oral doses represents a promising approach to weight maintenance therapy. We look forward to exploring this further in an upcoming maintenance dosing study."

Exploratory dosing cohort evaluates weight maintenance

The trial also included an exploratory cohort which evaluated weight loss maintenance in participants who were rapidly titrated to 90 mg of VK2735 once daily. Results from this patient population show:

After four weeks at 90 mg, participants were down-titrated to 30 mg once daily and maintained at that dose for seven weeks.
Weight loss was rapid and progressive during the 90 mg dosing period.
Weight reduction was maintained after transitioning to 30 mg daily dosing.
Findings suggest that effective weight maintenance may also be possible at doses below 30 mg.

In terms of safety and tolerability, VK2735 demonstrated encouraging outcomes following 13 weeks of once-daily dosing. During the VENTURE-Oral Dosing study, 13% of participants in the placebo arm discontinued treatment due to an adverse event, compared with 20% of those receiving VK2735.

Trial design and study endpoints

The VENTURE-Oral Dosing trial was a randomized, double-blind, placebo-controlled, multicenter study evaluating VK2735 oral tablets.

The trial enrolled 280 adults who were either obese (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with at least one weight-related comorbidity.
Participants were randomized evenly across six VK2735 dosing arms or placebo.
Treatment was administered once daily for 13 weeks.
The primary endpoint was percent change in body weight from baseline at week 13.
Secondary and exploratory endpoints assessed additional safety and efficacy outcomes, as well as pharmacokinetics and tolerability.

Phase III VANQUISH program to follow

Earlier in June, Viking announced it would be progressing VK2735 into Phase III development through the VANQUISH clinical program which includes two studies: VANQUISH-1 (NCT07104500) and VANQUISH-2 (NCT07104383).²

VANQUISH-1 will be evaluating VK2735 in adults with obesity while VANQUISH-2 will be evaluating the GLP-1 in obese or overweight adults with type 2 diabetes. Both studies are randomized, double-blind, placebo-controlled, multicenter trials assessing VK2735 administered by subcutaneous injection once weekly for 78 weeks.

References

1. Viking Therapeutics Announces Positive Top-Line Results from Phase 2 VENTURE-Oral Dosing Trial of VK2735 Tablet Formulation in Patients with Obesity. News release. Viking Therapeutics. August 19, 2025. Accessed August 19, 2025. https://www.prnewswire.com/news-releases/viking-therapeutics-announces-positive-top-line-results-from-phase-2-venture-oral-dosing-trial-of-vk2735-tablet-formulation-in-patients-with-obesity-302533355.html

2. Viking Therapeutics Announces Initiation of Phase 3 Obesity Clinical Program with GLP-1/GIP Agonist VK2735. News release. Viking Therapeutics. June 25, 2025. Accessed August 19, 2025. https://www.prnewswire.com/news-releases/viking-therapeutics-announces-initiation-of-phase-3-obesity-clinical-program-with-glp-1gip-agonist-vk2735-302490496.html

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