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Review
. 2021 Sep;46(Suppl 2):151-158.
doi: 10.1007/s00059-020-04994-0. Epub 2020 Oct 12.

[Heart failure protection by SGLT2 inhibitors in patients with type 2 diabetes mellitus: evidence and possible mechanisms : A systematic review]

[Article in German]
Andreas J Rieth  1   2 , Christian W Hamm  3   4   5 , Christoph Wanner  6 , Veselin Mitrovic  3   4 , Till Keller  7   8   9
Affiliations
Review

[Heart failure protection by SGLT2 inhibitors in patients with type 2 diabetes mellitus: evidence and possible mechanisms : A systematic review]

[Article in German]
Andreas J Rieth et al. Herz. 2021 Sep.

Abstract
in English, German

Background: Renal sodium-glucose cotransporter‑2 (SGLT2) inhibitors seem to have a cardioprotective effect beyond the antidiabetic effect. The underlying mechanisms are unclear.

Methods: Selective search in PubMed with a focus on heart failure endpoints and possible mechanisms of action.

Results: During treatment with three of the substances analyzed, there were fewer hospitalizations for heart failure compared with placebo; however, the numbers needed to treat within the primary analyses were relatively high (72-117). We found that loss of weight and lowering of blood pressure were more pronounced during treatment with verum than with placebo and an association of the preventive effect with more severely impaired renal function.

Conclusion: The SGLT2 inhibitors show a moderate heart failure protective effect in diabetic patients. It is likely that a nephroprotective effect with modulation of the cardiorenal interaction is an important part of the mechanism of action but this must be substantiated in further investigations.

Zusammenfassung: HINTERGRUND: Hemmstoffe des renalen Natrium-Glukose-Kotransporters 2 („sodium glucose-linked transporter 2“; SGLT2i) scheinen außer der antidiabetischen auch eine kardioprotektive Wirkung zu besitzen; deren Mechanismus ist jedoch unklar.

Methoden: Selektive Literaturrecherche in PubMed (Fokus Herzinsuffizienz und Wirkmechanismen).

Ergebnisse: Unter Therapie mit 3 der untersuchten Substanzen kam es im Vergleich mit Placebo zu weniger herzinsuffizienzbedingten Krankenhausaufenthalten, allerdings mit einer relativ hohen Anzahl von Behandlungen pro verhindertes Ereignis (72–117). Außer einer stärkeren Gewichtsabnahme und Blutdrucksenkung unter dem Verum gegenüber Placebo fiel eine Zunahme des kardioprotektiven Effekts bei stärker eingeschränkter Nierenfunktion auf.

Schlussfolgerung: Ein moderater herzinsuffizienzpräventiver Effekt von Hemmstoffen des renalen SGLT2 kann bei Diabetikern als gesichert gelten. Ein wesentlicher Wirkmechanismus beruht wahrscheinlich auf einem nephroprotektiven Effekt mit Modulation der kardiorenalen Interaktion, was jedoch weiterer Abklärung bedarf.

Keywords: Canagliflozin; Cardioprotective effect; Cardiorenal interaction; Dapagliflozin; Empagliflozin.

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