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 lipo-/glyco-protein 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 lipo-/glyco-protein profiling was performed from stored serum.
Median age was 52 years and BMI 34 kg/m2; 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. Lipo-/glycol-protein 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 lipo-/glyco-protein 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 lipo-/glyco-protein species were observed that did not correlate with magnitude of changes in weight, liver fat or insulin resistance, suggesting an independent mechanism.
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 lipo-/glyco-protein profiling was performed from stored serum.
Median age was 52 years and BMI 34 kg/m2; 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. Lipo-/glycol-protein 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 lipo-/glyco-protein 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 lipo-/glyco-protein species were observed that did not correlate with magnitude of changes in weight, liver fat or insulin resistance, suggesting an independent mechanism.
Authors
Lake Lake, Kitch Kitch, Kantor Kantor, Alonso Alonso, Belaunzaran-Zamudio Belaunzaran-Zamudio, Kulik Kulik, Hyatt Hyatt, Fichtenbaum Fichtenbaum, Brown Brown, Landay Landay, Sattler Sattler, Erlandson Erlandson
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