Empagliflozin Improves Cognitive Impairment in Frail Older Adults With Type 2 Diabetes and Heart Failure With Preserved Ejection Fraction

Abstract

Objective: To assess whether the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin improves cognitive impairment in frail older adults with diabetes and heart failure with preserved ejection fraction (HFpEF).

Research design and methods: We designed a prospective study to assess cognitive and physical function in consecutive frail older adults with diabetes and HFpEF, comparing the effects of empagliflozin, metformin, and insulin.

Results: A total of 162 frail older adults with HFpEF and diabetes successfully completed the study. Montreal Cognitive Assessment scores at baseline and after 1 month were 19.80 ± 3.77 vs. 22.25 ± 3.27 (P < 0.001) in the empagliflozin group, 19.95 ± 3.81 vs. 20.71 ± 3.56 (P = 0.26) in the metformin group, and 19.00 ± 3.71 vs. 19.1 ± 3.56 (P = 0.81) in the insulin group. A multivariable regression analysis confirmed the beneficial effects of empagliflozin. Additionally, we observed a marked amelioration of physical impairment, assessed by the 5-m gait speed test, in the empagliflozin and metformin groups but not in the insulin group.

Conclusions: This study is the first to show significant beneficial effects of the SGLT2 inhibitor empagliflozin on cognitive and physical impairment in frail older adults with diabetes and HFpEF.

Trial registration: ClinicalTrials.gov NCT04962841.

Figure 1

MoCA score in the empagliflozin, metformin, and insulin groups evaluated at baseline and follow-up. Data are means ± SD. **P < 0.01, ***P < 0.001.

Figure 2

The 5mGS in the empagliflozin, metformin, and insulin groups measured at baseline and follow-up. Data are means ± SD. *P < 0.05, ***P < 0.001.

Figure 3

A: Dispersion model at baseline between MoCA score and 5mGS (r = 0.508, P < 0.001). B: Dispersion model at follow-up between MoCA score and 5mGS test results in the empagliflozin group (r = 0.711, P < 0.001).