What Is VK2735

Nearly 1 in 3 adults (30.7%) are overweight, and more than 2 in 5 adults (42.4%) have obesity. In the last decade the rate of adults with severe obesity has doubled affecting nearly 10% of the US population. A new class of pharmaceuticals, developed for the treatment of diabetes, have also shown incredible results, for weight loss. Incretin mimetics, (compounds that mimic incretin hormones) otherwise known as agonists, are a class of effective drugs, that mimic an incretin called GLP-1. Pharmaceuticals like dulaglutide (Trulicity), liraglutide (Victoza), and semaglutide (Ozempic), have gained increasing popularity showing remarkable results in the treatment of obesity. The newest addition to this drug family combines GLP-1 and another incretin mimic, GIP. VK2735 is a novel dual agonist of glucagon like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors for the potential treatment of various metabolic disorders, including diabetes and obesity. We’re going to speak more about what VK2735 does, how it works, and what the current clinical research shows.

What Is VK2735 

The fascinating thing about biopharmaceutical development, is the prospective therapeutic treatment of metabolic disorder, to advance human health and longevity.

VK2735 is a novel dual agonist of glucagon like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors for the potential treatment of various metabolic disorders, namely obesity.

Created and synthesized by Viking Therapeutics, the same biopharmaceutical company, that developed VK5211, better known as LGD-4033, the selective androgen receptor modulator (SARM), Ligandrol, VK2735 has shown extraordinary effects, indicated to treat obesity and is currently in Phase 2 clinical trials.

The concept and discovery of incretin in the treatment of diabetes, was discovered more than a century ago, by scientists Bayliss and Starling, in 1902. They hypothesized that gut extracts contain a hormone that regulates the endocrine pancreas and showed that administration of gut extracts reduces the amount of urine sugars in patients with diabetes, presumably through stimulation of the endocrine pancreas. In 1929, glucose lowering extracts, were purified, and named incretin.

Two hormones, gastric inhibitory polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1), have been shown to act as incretins.

GIP is a 42‐amino‐acid hormone secreted from K cells of the upper small intestine and found to stimulate insulin secretion and inhibit gastric acid secretion. GLP‐1, a 31‐amino‐acid hormone produced from proglucagon and secreted from L cells of the lower intestine and colon, directly acts on pancreas cells called islets and stimulates insulin secretion in isolated islets [R].

How Does VK2735 Work, What Does VK2735 Do

GLP-1 and GIP are known as incretin hormones. They are secreted from the intestine on ingestion of glucose or nutrients to stimulate insulin secretion from pancreatic beta cells. Incretin mimetics are similar to hormones, made by the gut and brain. They target hunger hormones like leptin and ghrelin, effect insulin sensitivity, and slow down gastric emptying [R].

A 28 day phase 1 study was conducted, with the primary endpoint to determine and evaluate safety, efficacy, and tolerability of single and multiple doses of VK2735. The secondary objective was to evaluate pharmacokinetics.

Activation of the glucagon-like peptide 1 (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.

GLP-1 stimulates insulin secretion (which then allows cells to take up glucose) and inhibits glucagon secretion (which prevents more glucose from going into the bloodstream) to lower blood sugar levels. GLP-1 also slows stomach emptying, meaning that less glucose from food is released into the bloodstream.

VK2735 is a novel dual agonist of glucagon like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. Thus, it mimics both GLP-1 and GIP receptors. 

Currently, Semaglutide, a GLP-1 receptor agonist has been approved by the U.S. Food and Drug Administration 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 glucose-dependent insulinotropic peptide (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 is approved by the U.S. Food and Drug Administration and is currently marketed as Mounjaro [R].

VK2735 Benefits

Type II Diabetes

Mechanistically, GLP-1 and GIP agonists, have shown that incretin mimetics is a viable treatment for diabetes. FDA approved pharmaceuticals, such as Semaglutide, Rybelsus®, Wegovy, and Tirzepatide, with similar mechanisms of action, improve glycemic control, insulin sensitivity, and can lower blood glucose levels.


Phase 1 clinical trials, to evaluate safety and efficacy showed outstanding results amongst obese patients, with treatment of VK2735. In a multiple dose protocol, VK2735 demonstrated encouraging safety and tolerability, after 28 days of administration, with a dose of 7.5mg. Patients saw an average reduction in body weight of 18 pounds from baseline.

With these study results, VK2735 has been established as a potential novel therapeutic treatment for diabetes and obesity.

With the ever-increasing rate of obesity, this new class of novel therapeutics, in the treatment of obesity, has brought us into a new era of elite obesity treatments. 

Is VK2735 FDA Approved For Clinical Use

On September 6, 2023, Viking Therapeutics announced, the initiation of a Phase 2 clinical trial of VK2735.

The Phase 2 VENTURE trial is a randomized, double-blind, placebo-controlled study that will evaluate the safety, tolerability, pharmacokinetics, and weight loss efficacy of four different doses of VK2735, administered subcutaneously, once weekly. 

The 13-week trial will 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 co-morbid condition.  The primary endpoint of the study is the percent change in body weight from baseline to Week 13, with secondary and exploratory endpoints evaluating a range of additional safety and efficacy measures [R].

VK2735: Takeaway

VK2735, has shown astonishing results, thus far as a potential therapeutic treatment for obesity. With the initiation of Phase 2 clinical trials, it will still be several years, until this product is released and commercially available, if therapeutic treatment and efficacy is further established, and approved by the FDA.

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