Trial reportBritish journal of clinical pharmacology2021
Endothelial-protective effects of a G-protein-biased sphingosine-1 phosphate receptor-1 agonist, SAR247799, in type-2 diabetes rats and a randomized placebo-controlled patient trial.
Trial report in British journal of clinical pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 14 citations in OpenAlex.
- Endothelial-protective effects of a G-protein-biased sphingosine-1 phosphate receptor-1 agonist, SAR247799, in type-2 diabetes rats and a randomized placebo-controlled patient trial.British journal of clinical pharmacology · 2021Trial
- Apolipoprotein M: Structural insights, functional roles, and therapeutic approaches in vascular disease.The Journal of biological chemistry · 2026Review
- Bioactive lipids and metabolic syndrome-a symposium report.Annals of the New York Academy of Sciences · 2022Article
- S1P Stimulates Erythropoietin Production in Mouse Renal Interstitial Fibroblasts by S1PInternational journal of molecular sciences · 2021Article
- Sphingolipids in metabolic disease: The good, the bad, and the unknown.Cell metabolism · 2021Review
- A label-free impedance assay in endothelial cells differentiates the activation and desensitization properties of clinical S1PFEBS open bio · 2020Article
- Article
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Authors and funding
23 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsSAR247799 is a G-protein-biased sphingosine-1 phosphate receptor-1 (S1P
methodsType-2 diabetes patients, enriched for endothelial dysfunction (flow-mediated dilation, FMD <7%; n = 54), were randomized, in 2 sequential cohorts, to 28-day once-daily treatment with SAR247799 (1 or 5 mg in ascending cohorts), placebo or 50 mg sildenafil (positive control) in a 5:2:2 ratio per cohort. Endothelial function was assessed by brachial artery FMD. Renal function, biomarkers and lymphocytes were measured following 5-week SAR247799 treatment (3 doses) to Zucker diabetic fatty rats and the data used to select the doses for human testing.
resultsThe maximum FMD change from baseline vs placebo for all treatments was reached on day 35; mean differences vs placebo were 0.60% (95% confidence interval [CI] -0.34 to 1.53%; P = .203) for 1 mg SAR247799, 1.07% (95% CI 0.13 to 2.01%; P = .026) for 5 mg SAR247799 and 0.88% (95% CI -0.15 to 1.91%; P = .093) for 50 mg sildenafil. Both doses of SAR247799 were well tolerated, did not affect blood pressure, and were associated with minimal-to-no lymphocyte reduction and small-to-moderate heart rate decrease.
conclusionThese data provide the first human evidence suggesting endothelial-protective properties of S1P
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