Background: SGLT2i is associated with CV benefits, but the mechanisms are not fully elucidated. We report a novel finding associated with improved CV Health in T2D & HFrEF. Elevated ketones, EF%, & heart remodeling have been reported with SGLT2i. This is likely, in part, due to a switch in cardiac metabolism to ketone oxidation. This switch might be present in peripheral tissues, including skeletal muscle (SkM).

Objective: To examine the effects of SGLT2i on SkM energy production, utilization, exercise recovery, lipid content, and cardiopulmonary function.

Methods n=10(Age= 61.6±3.5, BMI= 31.4±1.8, A1c=7.6%±0.4, EF 32.7%±2.7) were randomized to empagliflozin 25mg vs. placebo 2:1 for 12 wks. SkM 31P & 1H MRS was performed. Cardiopulmonary exercise testing (CPET) was done to assess functional capacity and determine CV prognosis.

Results: After SGLT2i, there was a significant improvement in SkM energy production, utilization at rest, and exercise recovery. The VE/VCO2 slope, significantly improved (p<0.05) (Fig.1)

Conclusion: We show for the first time that, in subjects with T2DM & HFrEF, SGLT2i significantly improve SkM bioenergetics and lipid content. This was associated with a significant improvement in CV prognostic markers. These findings may explain novel mechanisms of improvement in peripheral bioenergetics that translate into Global CV Health.

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Disclosure

Y. Qin: None. N.D. Sanchez: None. F.M. Acosta: None. A. Moody: None. S. Neppala: None. C.L. Triplitt: Speaker's Bureau; Novo Nordisk. Consultant; Eli Lilly and Company. Other Relationship; American Diabetes Association. G.D. Clarke: None. E. Cersosimo: None. R.A. DeFronzo: Advisory Panel; AstraZeneca, Novo Nordisk, Boehringer-Ingelheim, Intarcia Therapeutics, Inc., Aardvark, Renalytix, Corcept Therapeutics, Alnylam Pharmaceuticals, Inc. Research Support; Boehringer-Ingelheim, AstraZeneca, 89bio, Inc., Amgen Inc., Medality, Corcept Therapeutics. Speaker's Bureau; AstraZeneca, Corcept Therapeutics, Renalytix. C. Solis-Herrera: Advisory Panel; Novo Nordisk, Bayer Inc.

Funding

Doris Duke Foundation

© 2024 by the American Diabetes Association
2024
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