Semaglutide improves markers of cardiovascular risk in people with HIV

Semaglutide improves cardiovascular disease (CVD) risk in people who are diabetic, overweight, or obese through incompletely understood mechanisms. To address this, we explored novel lipidomic and lipoprotein/glycoprotein profiling with semaglutide therapy.

Secondary analysis of SLIM LIVER (ACTG A5371), an open-label, phase 2b, single-arm trial of 1 mg semaglutide weekly in adult people with HIV (PWH) and metabolic dysfunction-associated steatotic liver disease.

Participants ( n  = 36) experiencing clinical response (>5 lb weight loss) to semaglutide were included. Lipidomic and lipoprotein/glycoprotein profiling was performed from stored serum.

Median age was 52 years and BMI 34 kg/m 2 ; 39% were Hispanic, 28% Black, 45% female, and 22% had stable statin use. Lipidomics: semaglutide reduced triglycerides, diglycerides, and sphingomyelins and increased some bile acids and phosphatidylcholines. Lipoproteins: CVD-linked species decreased; LDL particle size increased and large HDL particle number decreased. Glycoproteins: most participants had elevated baseline GlycA and GlycB, CVD-associated markers of systemic inflammation. 56% with elevated Glyc A improved and 32% normalized; 41% with elevated Glyc B improved and 42% normalized. Lipoprotein/glycoprotein concentrations generally did not correlate with baseline weight, liver fat, or insulin resistance or their magnitude of change.

In this first human report of lipidomic and lipoprotein/glycoprotein profiling during semaglutide therapy in any population, lipidomic changes suggest reductions in toxic lipid species and improved hepatic insulin sensitivity. Significant reductions in CVD-risk associated lipoprotein/glycoprotein species were observed that did not correlate with magnitude of changes in weight, liver fat. or insulin resistance, suggesting an independent mechanism.