Objective: GLP-1RAs are recommended as first-line therapy for cardiorenal risk reduction in people with T2D. We have shown that SGLT2 inhibitor therapy increased circulating vascular regenerative (VR) cell content in individuals with T2D. The ORIGINS-RCE trial recently reported that VR cell content was decreased in South Asian (SA) individuals compared to people of White European (WE) origin. This sub-analysis sought to determine the impact of GLP-1RA and SGLT2 inhibitor therapy on VR cell content in SA vs. WE individuals with T2D.

Methods: ORIGINS-RCE enrolled 120 individuals of SA or WE ethnicity with T2D and/or CVD. Within this cohort, 88 had T2D amongst whom 22 were on a GLP-1RA, 39 on an SGLT2 inhibitor, and 27 on neither. Multi-parametric flow cytometry was used to enumerate pro-vascular vs. pro-inflammatory progenitor cell subsets.

Results: The absolute count of VR cells (ALDHhiSSClowCD133+ cells/106 MNC) in the GLP-1RA group (310 ±56) was similar to that in the SGLT2 inhibitor group (244 ± 23; P=0.32), but greater than that in the neither therapy group (216 ± 33; P=0.027). The GLP-1RA group also had greater endothelial progenitor cell content (ALDHhiSSClowCD34+CD45-CD133+; 11 ± 3) compared to the neither therapy group (7 ± 2; P=0.011). The pro-inflammatory burden of ALDHhiSSChi precursor cells in the GLP-1RA group (41845 ± 12616) was lower than that of the neither therapy (53900 ± 7249; P=0.015). While there was no difference in ALDHhiSSClowCD133+ content between WE and SA individuals within the GLP-1RA and neither therapy groups, there were less of these cells among the SA (vs. WE) individuals in the SGLT2 inhibitor group (202 ±28 vs. 318 ± 31; P=0.010), suggesting a lack of a protective response of SGLT2 inhibitor therapy in SA people.

Conclusion: In individuals with T2D, VR progenitor cell content varied according to medication use and ethnic origin. These data uncovered conserved cardioprotective benefits of GLP-1RA therapy in high-risk SA individuals.

Disclosure

A. Krishnaraj: None. B. Park: None. E. Bakbak: None. R. Verma: None. A. Quan: None. H. Teoh: Other Relationship; Canadian Medical and Surgical Knowledge Translation Research Group. D.A. Hess: None. S. Verma: Other Relationship; Amarin Corporation, Amgen Inc., AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Canadian Medical and Surgical Knowledge Translation Research Group, Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Novartis AG, Novo Nordisk, Pfizer Inc., PhaseBio Pharmaceuticals, Inc., S&L Solutions Event Management, Sanofi.

Funding

CIHR (#369189 and #186065); Heart and Stroke Foundation (#G-23-0035127)

© 2024 by the American Diabetes Association
2024
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