Abstract 62: The Effect of ETC-1002 on Low Density Lipoprotein-Cholesterol and Additional Risk Factors in Patients With Type 2 Diabetes

Background Patients with type 2 diabetes (T2DM) are at high risk for cardiovascular (CV) disease and over half do not achieve LDL-C goal. Statins lower CV risk by reducing LDL-C and inflammation, but have been associated with worsening glycemic control and new onset diabetes, resulting in class label warnings for all statins. ETC-1002 is an oral investigational drug in Phase 2 development to treat dyslipidemia and other cardio-metabolic risk factors through dual adenosine monophosphate-activated protein kinase activation and adenosine triphosphate-citrate lyase inhibition. Methods Sixty T2DM patients received either ETC-1002 (80 mg for 2 weeks followed by 120 mg for 2 weeks) or placebo (PBO) for 4 weeks following a 4 week T2DM drug washout and 1 week PBO run-in. Results ETC-1002 lowered LDL-C by 43% (PBO corrected mean -39%; p<.0001) and non-HDL-C by 32% (PBO corrected mean -31%; p<.0001). Median reductions in high sensitivity C-reactive protein (hsCRP) were 41% and 11% for ETC-1002 and PBO (p=.0011). Post hoc analyses showed additional benefits of ETC-1002. An LDL-C goal of <100 mg/dL was achieved by 88% of ETC-1002 (21/24) and 4% of PBO subjects (1/24) not at baseline goal (p<.0001 versus PBO). Reductions in post-prandial hyperglycemia following standard meal challenge were observed which were significant in a subgroup of patients with BMI ≥ 30 kg/m 2 (p=.0246 versus placebo). Using continuous glucose monitoring, ETC-1002 treatment resulted in significant peak glycemic reduction between hours 6-12 and a trend between hours 12-18 and 18-24. A weight loss trend was observed with ETC-1002. In patients with 24 hour diastolic ambulatory blood pressure (DBP) > 80 mmHg, a 7 mmHg reduction versus PBO was observed (p=.0474). ETC-1002 was safe and well tolerated with no drop-outs, dose limiting side effects or serious adverse events, and no liver function tests >2 times upper limit normal. Conclusion In patients with T2DM and dyslipidemia, ETC-1002 produced statin-like reduction in LDL-C, robust reduction in hsCRP and was associated with modest to significant improvement of blood pressure, glucose control and weight loss. The novel mechanism of action of ETC-1002 may provide unique benefit to these patients.