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Background: Gemcabene (GEM), an ApoC-III and CRP modulator, showed significant LDL-C, ApoB, TG and hsCRP lowering and trends of glucose lowering in dyslipidemic subjects. In preclinical studies, 3T3L1 differentiated adipocytes treated with 100µM GEM plus insulin resulted in a 25% increase in [14C] deoxyglucose uptake compared to a 70% increase with 5 µM troglitazone, suggesting possible GEM insulin sensitization. To further investigate these observations, we assessed the GEM effect on average glucose disposal rate (GDR) during the last 30 minutes of a 3-hour euglycemic hyperinsulinemic clamp in healthy, obese, non-diabetic subjects.
Methods: Fifty-three subjects with BMI 30 to 40 kg/m2 and fasting glucose <126 mg/dL were randomized 1:1 to GEM 900 mg or PBO orally QD for 4 weeks. A clamp study was performed prior to treatment and 1 hour following the last GEM dose. The % change from baseline in GDR was compared for GEM and PBO using a 2-sample t-test.
Results: GEM 900 mg lowered LDL-C by 40% compared to placebo (p < 0.0001). The point estimate of the mean difference in the % change from baseline in the GDR was in favor of GEM, but did not attain statistical significance.
Conclusions: GEM 900 mg QD was generally well-tolerated and associated with a 6.76% mean increase in GDR compared to placebo. Although statistical significance was not observed in this pilot study, results support further exploration of GEM on glucose and insulin sensitization in a larger study in diabetic subjects.
Poster Hall, Hall C
Sunday, March 19, 2017, 9:45 a.m.-10:30 a.m.
Session Title: Diabetes and Other Issues in Cardiovascular Prevention
Abstract Category: 32. Prevention: Clinical
Presentation Number: 1277-059
- 2017 American College of Cardiology Foundation