Abstract Body (Do not enter title and authors here): Background: The incidence of diabetes mellitus (DM) continues to rise and is one of the most prevalent and costly chronic diseases worldwide. Diabetes, obesity, and cardiovascular disease (CVD) are closely linked, with CVD being the leading cause of mortality in individuals with DM. Thus, treatment (tx) of obesity has become a cornerstone in the prevention and management of type T2DM and CVD. Novel incretin mimetics, such as VK2735, a long-acting dual agonist of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptors, may positively impact the risk of CVD in adults with T2DM.
Hypothesis: Capture of cardiometabolic (CM) parameters in studies with VK2735 will provide critical data to determine improvement in CM measures and may support the potential long term benefit on CVD-related outcomes.
Methods: VANQUISH-2 is a Phase 3, 78-week randomized, double-blind, placebo-controlled, parallel arm study that will evaluate the weight loss efficacy, safety, tolerability, pharmacodynamic effects, and pharmacokinetics of VK2735 in adults who are obese or overweight with T2DM. Participants will be recruited from sites in U.S. and will be randomized to receive a weekly subcutaneous injection of placebo or VK2735 (7.5-, 12.5-, or 17.5-mg). The tx period at the final target dose for each group will be a minimum of 52 weeks. Participants will receive lifestyle counseling throughout the tx period and should participate in ≥150 of physical activity per week in addition to a balanced, hypocaloric diet. Key inclusion criteria are adults with BMI ≥27 kg/m2. Key exclusion criteria are current or past diagnosis of type 1 DM, severe hypertriglyceridemia, prior or planned surgical tx or endoscopic and/or device-based tx for obesity and eGFR <30mL/min/1.73m2.
Results: The primary efficacy endpoint of the study is mean percent change in body weight from baseline to end of tx. Key secondary endpoints are percentage of participants that achieve ≥5%, ≥10%, ≥15% and ≥20% body weight reduction by end of tx. Assessed changes in T2DM and CM-related parameters will include HbA1c, BMI, waist circumference, blood pressure and lipid profile. Safety and tolerability will also be assessed. Pancreatitis, gallbladder and CV events will be adjudicated.
Conclusions: VANQUISH-2 will provide the first Phase 3 efficacy and safety data, including CM parameters, of the dual GIP/GLP-1 receptor agonist VK2735 for weight loss in obese or overweight adults with T2DM.