SGLT2 inhibitors and lower limb complications: the diuretic-induced hypovolemia hypothesis.

Abstract

In a recent meta-analysis of randomized controlled trials of sodium glucose co-transporter 2 inhibitors (SGLT2i) in patients with diabetes, Lin and colleagues showed a positive association between SGLT2i-induced blood pressure and weight reduction and the risk of lower limb events. These results support the potential mechanism of a volume depletion effect of SGLT2i to explain the increase risk of amputation observed with this pharmacological class. Since the first result of the CANVAS trial raised a concern regarding the risk of amputation with SGLT2i, this hypothesis emerged from studies showing a higher incidence of amputations in patients with diabetes using diuretics. Furthermore, recent data found that copeptin, a surrogate marker of hydration status was also associated with lower limb outcomes. In conclusion, this assumption of diuretic-induced hypovolemia explanation highlights the fact that medications that induce a contraction of plasma volume, both traditional and novel agents with a diuretic mode of action should be introduced cautiously in patients with diabetes at high risk of diabetic foot events.

• Authors: Louis Potier, Kamel Mohammedi, Gilberto Velho, Ronan Roussel
• Journal: Cardiovascular diabetology (Cardiovasc Diabetol) Vol. 20 Issue 1 Pg. 107 (05 13 2021) ISSN: 1475-2840 [Electronic] England
• PMID: 33985506 (Publication Type: Journal Article, Comment)

Chemical References

• Diuretics
• Sodium-Glucose Transporter 2 Inhibitors

Topics

• Diabetes Mellitus, Type 2
• Diuretics
• Humans
• Hypovolemia
• Lower Extremity
• Sodium-Glucose Transporter 2 Inhibitors