Introduction & Objective: Dysregulated lipid profiles in obesity can cause systemic inflammation and elevate cardiovascular (CV) risk. We studied the impact of pemvidutide, a dual GLP-1/glucagon receptor agonist, on lipoprotein and glycoprotein biomarkers of CV inflammation.
Methods: Subjects with overweight or obesity and without diabetes (N=34) were randomly assigned 1:1:1:1 to pemvidutide (1.2, 1.8, 2.4 mg) or placebo administered subcutaneously weekly for 12 weeks. Lipidomic and glycoprotein profiling was conducted using ultra-high performance liquid chromatography-mass spectrometry or NMR on plasma samples at Day -1, Day 43, and Day 85.
Results: Pemvidutide reduced body weight by up to 10.3% and the atherogenic lipids total cholesterol, LDL-C, and triglycerides by up to 28%, 26%, and 38%, respectively. Pemvidutide reduced pro-inflammatory lipidomic signatures such as small-dense LDL-C, short-chain, saturated diglycerides, lysophosphatidylinositols, lysophosphatidylcholines and sphingolipids. Reduction in GlycA and GlycB, biomarkers of systemic inflammation correlated with heart failure, were also observed (Table 1).
Conclusion: Pemvidutide elicited significant weight loss and decreases in pro-inflammatory lipid species associated with atherogenesis and CV risk. These results may reflect beneficial effects of glucagon on lipoprotein and glycoprotein metabolism.
J.J. Suschak: Employee; Altimmune Inc. B. Georges: Employee; Altimmune. M.S. Roberts: Employee; Altimmune Inc. M. Harris: Employee; Altimmune Inc. S.K. Browne: Employee; Altimmune Inc.
