Safety of four SGLT2 inhibitors in three chronic diseases: A meta-analysis of large randomized trials of SGLT2 inhibitors.

Publisher: Sage Publications Country of Publication: England NLM ID: 101234011 Publication Model: Print Cited Medium: Internet ISSN: 1752-8984 (Electronic) Linking ISSN: 14791641 NLM ISO Abbreviation: Diab Vasc Dis Res Subsets: MEDLINE

Publication: 2009- : London : Sage Publications
Original Publication: Edgbaston, Birmingham, UK : Sherborne Gibbs, c2005-

Diabetes Mellitus, Type 2/*drug therapy ; Heart Failure/*drug therapy ; Renal Insufficiency, Chronic/*drug therapy ; Sodium-Glucose Transporter 2 Inhibitors/*therapeutic use; Acute Kidney Injury/epidemiology ; Acute Kidney Injury/prevention & control ; Amputation, Surgical ; Diabetes Mellitus, Type 2/diagnosis ; Diabetes Mellitus, Type 2/epidemiology ; Diabetic Ketoacidosis/epidemiology ; Fractures, Bone/epidemiology ; Heart Failure/diagnosis ; Heart Failure/epidemiology ; Humans ; Hypoglycemia/epidemiology ; Hypoglycemia/prevention & control ; Patient Safety ; Randomized Controlled Trials as Topic ; Renal Insufficiency, Chronic/diagnosis ; Renal Insufficiency, Chronic/epidemiology ; Reproductive Tract Infections/epidemiology ; Risk Assessment ; Risk Factors ; Sodium-Glucose Transporter 2 Inhibitors/adverse effects ; Treatment Outcome ; Urinary Tract Infections/epidemiology

There are no relevant meta-analyses that have assessed the safety of the sodium-glucose transporter 2 (SGLT2) inhibitors in different chronic diseases. We aimed at evaluating the safety of four SGLT2 inhibitors in three chronic diseases by meta-analysis of the large randomized trials of SGLT2 inhibitors. We performed random-effects meta-analysis and carried out subgroup analysis according to type of underlying diseases and type of SGLT2 inhibitors. SGLT2 inhibitors versus placebo significantly reduced the risk of acute kidney injury (RR 0.75, 95% CI 0.66-0.85), and showed the reduced trend in the risk of severe hypoglycemia (RR 0.86, 95% CI 0.71-1.03). SGLT2 inhibitors significantly increased the risks of diabetic ketoacidosis (RR 2.57), genital infection (RR 3.75), and volume depletion (RR 1.14); and showed the increased trends in the risks of fracture (RR 1.07), amputation (RR 1.21), and urinary tract infection (RR 1.07). These effects exhibited by SGLT2 inhibitors were consistent across three chronic diseases (i.e. type 2 diabetes, chronic heart failure, and chronic kidney disease) and four SGLT2 inhibitors (i.e. dapagliflozin, empagliflozin, ertugliflozin, and canagliflozin) (all P subgroup  > 0.05). These findings will guide that specific adverse events are monitored when SGLT2 inhibitors are used in clinical practice.

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Keywords: SGLT2 inhibitors; acute kidney injury; diabetic ketoacidosis; genital infection; volume depletion

0 (Sodium-Glucose Transporter 2 Inhibitors)

Date Created: 20210423 Date Completed: 20210903 Latest Revision: 20221207

20240628

PMC8481734

10.1177/14791641211011016

33887983