VK2735 (Subcutaneous & Oral Formulations)
Dual GLP-1/GIP Receptor Agonist

Obesity and Metabolic Disorders


Overview & Profile

We are developing a unique series of novel dual agonists of the glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors for the potential treatment of various metabolic disorders such as obesity, NASH, and certain rare disorders.

Our lead clinical program’s drug candidate is VK2735. Data announced during the first quarter of 2023, from a Phase 1 trial evaluating VK2735 (dosed subcutaneously) for metabolic disorders, demonstrated an encouraging safety and tolerability profile as well as positive signs of clinical benefit. 

Based on these promising initial Phase 1 data, the company initiated the Phase 2 VENTURE trial of VK2735 in patients with obesity in September 2023. The Phase 2 VENTURE trial is a randomized, double-blind, placebo-controlled study intended to evaluate the safety, tolerability, pharmacokinetics, and weight loss efficacy of VK2735, administered subcutaneously, once weekly. The 13-week trial was designed to enroll approximately 125 adults who are obese (BMI ≥30 kg/m2), or adults who are overweight (BMI ≥27 kg/m2) with at least one weight-related comorbid condition. Due to heightened clinician and patient interest, the trial’s enrollment size was increased to 176 from the original target. The primary endpoint of the study will assess the percent change in body weight from baseline to Week 13 among patients treated with VK2735 as compared with placebo, with secondary and exploratory endpoints evaluating a range of additional safety and efficacy measures. The VENTURE trial will evaluate weekly VK2735 doses of up to 15 mg, compared to the 10 mg top dose evaluated in the prior Phase 1 multiple ascending dose (MAD) study.

The Phase 1 trial of VK2735 was a randomized, double-blind, placebo-controlled single ascending dose (SAD) and multiple ascending dose (MAD) study in healthy adults. The SAD portion of the study evaluated VK2735 in healthy adults, while the MAD portion of the study enrolled healthy adults with a minimum body mass index (BMI) of 30 kilograms per meter squared (kg/m2). The primary objectives of the study were to evaluate the safety and tolerability of single and multiple doses of VK2735 administered subcutaneously, and identify suitable doses for further clinical development. The secondary objective was to evaluate the pharmacokinetics of VK2735 in healthy subjects. The SAD portion of the study evaluated escalating single doses of VK2735. In the MAD portion of the study subjects received VK2735 once weekly for 28 days.

Viking selected VK2735 from a series of internally developed dual GLP-1/GIP receptor agonists evaluated as part of a program focused on the development of best-in-class therapies for metabolic diseases. The results of certain in vivo studies from this program were presented at ObesityWeek® 2021, highlighting the promising effects observed following treatment with VK2735 and other compounds from the series. Data demonstrated improvements in the metabolic profile of diet-induced obese (DIO) mice treated with Viking’s compounds as compared to control cohorts.

GLP-1 and GIP are gut hormones secreted from intestinal L cells and K cells, respectively. Together, these hormones account for most of the enhanced insulin secretion observed in healthy adults after a meal.1 The receptors have complementary distribution and activities.2

Oral Formulation of VK2735

Also during the first quarter of 2023, Viking initiated a Phase 1 clinical study to evaluate a novel oral formulation of VK2735. The company believes the potential to provide both a subcutaneously injected and an oral dosage form represent a significant expansion of the opportunity for VK2735.

This study is an extension of the Phase 1 trial described above. The study is a randomized, double-blind, placebo-controlled study in healthy adults with a minimum BMI of 30 kg/m2. The primary objective of the study is to evaluate the safety and tolerability of VK2735 administered as an oral tablet once daily for 28 days. The secondary objective is to evaluate the pharmacokinetics of orally administered VK2735 in healthy subjects. Exploratory pharmacodynamic measures include assessments of changes in body weight and plasma glucose.

GLP-1/GIP Receptor Co-Activation and Downstream Effects

Samms RJ, Coghlan MP, Sloop KW. How May GIP Enhance the Therapeutic Efficacy of GLP-1? Trends in Endocrinology & Metabolism. 2020;31(6):410-421 (link).

Activation of the GLP-1 receptor has been shown to decrease glucose, reduce appetite, lower body weight and improve insulin sensitivity in patients with type 2 diabetes, obesity, or both. Semaglutide is a GLP-1 receptor agonist that has been approved by the U.S. Food and Drug Administration (FDA) and is currently marketed in various dosage strengths and forms as Ozempic®, Rybelsus®, and Wegovy®. More recently, research efforts have explored the potential co-activation of the GIP receptor as a means of enhancing the therapeutic benefits of GLP-1 receptor activation. Tirzepatide is a dual GLP-1/GIP receptor agonist that has been recently approved by the FDA and is currently marketed as Mounjaro™. There is growing excitement around the therapeutic promise of single agents designed to target multiple metabolic receptors, and preclinical data thus far suggest that VK2735 has best-in-class potential as a dual GLP-1/GIP agonist.

Clinical Data

In 2022, Viking initiated a Phase 1 SAD and MAD clinical trial of VK2735. During the first quarter of 2023, the company announced results from this study, which demonstrated that treatment with VK2735 was safe and well-tolerated when dosed for up to 28 days in healthy obese volunteers. In addition, treatment with VK2735 led to mean weight loss of up to 18 pounds from baseline.

In the SAD portion of the Phase 1 study, VK2735 demonstrated promising safety and tolerability, as well as a predictable pharmacokinetic profile. Following single subcutaneous doses, VK2735 demonstrated a half-life of approximately 170 to 250 hours, a Tmax (time to reach maximum plasma concentration) ranging from approximately 75 to 90 hours, and excellent therapeutic exposures.

In the 28-day MAD portion of the study, VK2735 demonstrated encouraging safety and tolerability, and positive signs of clinical activity. All cohorts receiving VK2735 experienced reductions in mean body weight from baseline, ranging up to 7.8%. Cohorts receiving VK2735 also demonstrated reductions in mean body weight relative to placebo, ranging up to 6.0%. Statistically significant differences compared to placebo were maintained or improved at the Day 43 follow-up time point, 21 days after the last dose of VK2735 was administered.  The company believes that the tolerability data from this study indicate that higher doses may be achieved with longer titration windows, and Viking plans to evaluate further dose escalation in the upcoming Phase 2 trial.

Importantly, VK2735 demonstrated encouraging safety and tolerability following repeated dosing. The majority of observed adverse events (98%) were reported as mild or moderate, and the majority of GI related adverse events (99%) were also reported as mild or moderate. No subjects were discontinued for nausea, vomiting, or GI adverse events. Notably, despite robust activation of the incretin receptor pathways, no hypoglycemia was reported.

Preclinical Data

Viking presented 2 posters (#2063 and #2074) with preclinical data from a series of internally developed dual agonists of the GLP-1 and GIP receptors at ObesityWeek® 2021 (November).5 The presentations highlight the effects of treatment on body weight and metabolic profile in diet-induced obese (DIO) mice as compared to control cohorts treated with vehicle, the GLP-1 agonist semaglutide, or the dual GLP-1/GIP agonist tirzepatide.

The results of the studies demonstrate that addition of GIP receptor activity improves upon the observed effects resulting from activation of the GLP-1 receptor alone in DIO mouse models. Weight loss, glucose, and insulin effects are enhanced in the Viking series of dual-agonist compounds compared to the effects observed with the GLP-1 agonist comparator, semaglutide, when administered at the same dose for the same time period.3 In separate studies, the effect sizes observed with the Viking series of dual agonists were similar to those observed following treatment with tirzepatide, a dual GLP-1/GIP receptor agonist. Reductions in liver fat content were generally numerically larger among animals treated with Viking compounds relative to liver fat reductions observed among tirzepatide-treated animals.4

Overweight and Obesity6

Overweight and obesity are defined as abnormal or excessive fat accumulation that may impair health. For adults, the definition of overweight is a body mass index (BMI) ≥ 25, and obesity is a BMI ≥ 30 (BMI is defined as a person’s weight in kilograms divided by the square of his height in meters, kg/m2).

Some recent (2016) global estimates are:

  • More than 1.9 billion adults aged 18 years and older were overweight. Of these over 650 million adults were obese.
  • 39% of adults aged 18 years and over (39% of men and 40% of women) were overweight.
  • Overall, about 13% of the world’s adult population (11% of men and 15% of women) were obese.
  • The worldwide prevalence of obesity nearly tripled between 1975 and 2016.

Some of the common health consequences of overweight and obesity are cardiovascular diseases (mainly heart disease and stroke), diabetes, musculoskeletal disorders (especially osteoarthritis, a highly disabling degenerative disease of the joints), and some cancers.


  1. Frias JP, Bastyr III EJ, Vignati L, Tschöp MH, et al. The Sustained Effects of a Dual GIP/GLP-1 Receptor Agonist, NNC0090-2746, in Patients with Type 2 Diabetes. Cell Metab. 2017;26(2):343–352 (link).   
  2. Samms RJ, Coghlan MP, Sloop KW. How May GIP Enhance the Therapeutic Efficacy of GLP-1? Trends Endocrinol. Metab. 2020;31(6):410-421 (link).
  3. Yagiz K, Barker G, Barnes M, Stevens E, et al. Novel Co-agonists of GLP-1 and GIP Receptors Produce Robust Weight Loss in a Rodent Model of Obesity. Poster (#206) presented at the annual meeting of The Obesity Society (ObesityWeek® 2021) (link).
  4. Yagiz K, Barker G, Barnes M, Stevens E, et al. Novel Dual Incretin Receptor Agonists Reduce Body Weight and Improve Metabolic Profile in DIO Mice. Poster (#207) presented at the annual meeting of The Obesity Society (ObesityWeek® 2021) (link).
  5. Viking Therapeutics Presents Preclinical Data on Novel Dual GLP-1/GIP Agonists at ObesityWeek® 2021. Viking Therapeutics press release, 11/1/2021 (link).
  6. World Health Organization (WHO): Obesity and overweight (link).