Predictors of cardio-kidney complications and treatment failure in patients with chronic kidney disease and type 2 diabetes treated with SGLT2\xa0inhibitors

Csaba Kovesdy,Linda Fried,Kerstin Folkerts,Michael Batech,Kevin Bowrin,Hanaya Raad,Niklas Schmedt

doi:10.1186/s12916-021-02191-2

Abstract

BackgroundClinical practice guidelines recommend sodium-glucose co-transporter 2 inhibitors (SGLT2is) to mitigate adverse kidney and cardiovascular outcomes in patients with type 2 diabetes (T2D), including patients with comorbid chronic kidney disease (CKD), also referred to as diabetic kidney disease (DKD), who are at even higher risk. In this study, we sought to identify predictors of cardio-kidney events, cardio-kidney complications, and treatment failure (i.e., addition/initiation of a new T2D class, insulin, or discontinuation of SGLT2is) after new initiation of SGLT2is in patients with CKD and T2D (DKD).MethodsIn this retrospective cohort study, we identified adult patients with DKD who initiated SGLT2is between April 1, 2012, and June 30, 2019, in Optum claims data. Outcome rates per 1000 person-years (PY) are reported with 95% confidence intervals (CIs). Cox proportional hazards regression identified patient characteristics associated with each outcome.ResultsThe study population consisted of 6389 initiators of SGLT2is. The rate of CV hospitalization was 26.0 (95% CI 21.6, 30.4) per 1000 PY. Baseline characteristics associated with higher risk of CV hospitalization included age, atrial fibrillation, peripheral vascular disease (PVD), and cancer. The rate of kidney hospitalization was 12.0 (95% CI 9.0, 15.0) per 1000 PY. The risk increased significantly with baseline evidence of heart failure, hyperkalemia, respiratory failure, depression, and use of loop diuretics. In total, 55.0% of all SGLT2i initiators discontinued treatment during the follow-up period. The rate of treatment failure was 510.5 (95% CI 492.9, 528.1) per 1000 PY. Analysis of key time-dependent SGLT2i-associated adverse events showed that experiencing diabetic ketoacidosis and volume depletion were associated with risk of treatment failure.ConclusionsOur study demonstrated high rates of residual cardio-kidney outcomes and treatment failure in patients with DKD treated with SGLT2is. Patients with high baseline CV risk and the presence of certain conditions, such as atrial fibrillation, PVD, and heart failure, were at higher risk for cardio-kidney events. Further research is needed to assess the potential relationship between adverse events and SGLT2i treatment failure.

Highlights

Clinical practice guidelines recommend sodium-glucose co-transporter 2 inhibitors (SGLT2is) to mitigate adverse kidney and cardiovascular outcomes in patients with type 2 diabetes (T2D), including patients with comorbid chronic kidney disease (CKD), referred to as diabetic kidney disease (DKD), who are at even higher risk
CKD progression differs by factors such as age [2], gender, and genetic [3] characteristics and entails compromised kidney function or kidney injury attributed to persistent uncontrolled hyperglycemia, the presence and/or release of proinflammatory proteins and pro-fibrotic proteins, and hypertension or high intra-glomerular pressure associated with elevated rates of cardiovascular disease (CVD) compared to T2D alone [4]
The study population consisted of 6389 patients with DKD at baseline who newly initiated Sodium-glucose co-transporter 2 inhibitors (SGLT2is) patients

Summary

Introduction

Clinical practice guidelines recommend sodium-glucose co-transporter 2 inhibitors (SGLT2is) to mitigate adverse kidney and cardiovascular outcomes in patients with type 2 diabetes (T2D), including patients with comorbid chronic kidney disease (CKD), referred to as diabetic kidney disease (DKD), who are at even higher risk. Determining the factors associated with cardiokidney complications and treatment failure after the initiation of SGLT2is may help to better understand the overall unmet need of SGLT2i-treated patients despite the availability of this risk-reducing medication. To better understand these factors, we sought to identify predictors of cardio-kidney events and predictors of treatment failure among initiators of SGLT2i with DKD using US-based real-world data

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