Mechanisms

Letters to the Editor Gliflozins for the Treatment of Congestive Heart Failure and Renal Failure in Type 2 Diabetes by Anna Katharina Seoudy, Prof. Dr. med. Dominik M. Schulte, Dr. med. Tim Hollstein, Dr. med. Ruwen Böhm, Prof. Dr. med. Dr. rer. nat. Ingolf Cascorbi, and Prof. Dr. med. Matthias Laudes in issue 8/2021

The extensive review article (1) did not make any mention of potential mechanisms of the gliflozins underlying cardioprotection. It is worth pointing out that neither the healthy myocardium nor the failing one possess SGLT2. To explain a decrease in myocardial inflammation, cardiac remodeling, and the effect on oxidative stress, a recently published critique discusses the importance of erythrocytosis induced by gliflozins in association with the activation of sirtuin-1 and hypoxia-inducible factor 2 (HIF-2a) on the release of cells from damaged organelles (mitochondria and perixosomes), known as autophagy (2).

Regarding euglycemic ketoacidosis, the importance of the much publicized low carb diets or ketogenic diets should be considered in addition to other predisposing factors.

In my opinion it should also be pointed out that diabetes patients with worsened renal function have a 23% higher risk reduction for 3-point major adverse cardiac events (3P-MACE) than patients whose renal function remains intact (reduction of 9%) (3).

Finally I would like to mention the rare but potentially life-threatening necrotizing fasciitis of the perineum—also known as Fournier’s gangrene—and its possible association with the administration of gliflozins. Diabetes alone constitutes a risk factor in this context. Obesity, lacking genital hygiene, and immunodeficiency, alcohol abuse, liver failure, and renal failure all play a contributing role. It is reassuring that a cohort study including almost 2 million diabetes patients did not find an increased risk for hospital admission for Fournier’s gangrene for patients treated with gliflozins compared with patients receiving other antidiabetic medications or insulin. The authors did, however, point out that more research is needed (4).

DOI: 10.3238/arztebl.m2021.0196

Dr. med. Athanasios Alexopoulos

Innere Medizin

Kurpark-Klinik Bad Nauheim

Conflict of interest statement

The author declares that no conflict of interest exists.

References

1. Seoudy AK, Schulte DM, Hollstein T, Böhm R, Cascorbi I, Laudes M: Gliflozins for the treatment of congestive heart failure and renal failure in type 2 diabetes. Dtsch Arztebl Int 2021; 118: 122–9

2. Parker M: Critical examination of mechanisms underlying the reduction in heart failure events with SGLT2 inhibitors: identification of a molecular link between their actions to stimulate erythrocytosis and to alleviate callular stress. Cardiovasc Res 2021; 117: 74–84

3. Giugliano D, De Nicola L, Maiorino M et al.: Preventing major adverse cardiovascular events by SGTL2 inhibition in patients with type 2 diabetes: the role of kidney. Cardiovasc Diabetol 2020, 19: 35–41

4. Wang T, Patel SM, Hickmann A: SGTL2 inhibitors and the risk of hospitalization for Fournier`s Gangrene: a nested-case-control study. Diabetes Ther 2020; 11: 711–23