Sodium-glucose co-transporter-2 (SGLT-2) inhibitors for patients with chronic kidney disease: a risk-stratified clinical practice guideline.

Article type
Authors
Agarwal A1, Zeng X2, Ponte B3, Li S4, Vandvik P5, Agoritsas T6
1Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada; MAGIC Evidence Ecosystem Foundation, Oslo, Norway
2MAGIC Evidence Ecosystem Foundation, Oslo, Norway; Department of Nephrology, West China Hospital, Sichuan University, Chengdu, China
3Division of Nephrology, Department of Medicine, Hôpitaux Universitaire de Genève and University of Geneva, Geneva, Switzerland
4Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China; Chinese Evidence-Based Medicine Center, Cochrane China Center and MAGIC China Center, West China Hospital, Sichuan University, Chengdu, China
5MAGIC Evidence Ecosystem Foundation, Oslo, Norway; Clinical Effectiveness Research Group, Institute of Health and Society, University of Oslo, Oslo, Norway
6MAGIC Evidence Ecosystem Foundation, Oslo, Norway; Division General Internal Medicine & Division of Clinical Epidemiology, University Hospitals of Geneva, Geneva, Switzerland
Abstract
Background: Recent trials have demonstrated cardio-renal benefits with sodium-glucose cotransporter 2 (SGLT-2) inhibitors among patients with chronic kidney disease (CKD), both with and without type 2 diabetes mellitus (T2DM). Existing guidance regarding SGLT-2 inhibitors for adults with CKD addresses use in patients with concomitant T2DM only, does not incorporate risk stratification, and does not consider long-term benefits and harms in absolute terms.

BMJ Rapid Recommendations, led by the MAGIC Evidence Ecosystem Foundation, accelerate the translation of evidence into practice by developing trustworthy recommendations. This work builds on 23 published Rapid Recommendations providing evidence-based practice guidance, and seeking to further develop guideline methodology in line with the GRADE approach.

Objectives: To produce risk-stratified practice guidance regarding the use of SGLT-2 inhibitors to improve cardio-renal outcomes and survival among adults living with CKD.

Methods: An international panel including patients, clinicians, and methodologists was convened to produce recommendations, following standards for trustworthy guidelines and using GRADE. After reviewing existing prognostic models, risk stratification schema and large-scale cohort data-sets, the panel ultimately adopted the 2012 Kidney Disease Improving Global Outcomes (KDIGO) classification to make recommendations for typical risk groups of patients (from low to very high risk of CKD progression and related complications).

Results: A systematic review and meta-analysis of 13 trials including 29,614 participants informed recommendations. SGLT-2 inhibitors, relative to placebo or standard care without SGLT-2 inhibitors, were associated with large relative reductions in risks of all-cause and cardiovascular mortality, hospitalization for heart failure, end-stage kidney disease, non-fatal myocardial infarction, and non-fatal stroke; risks of diabetic ketoacidosis, genital infections and symptomatic hypovolemia were higher.

For each pre-defined risk group, the guideline panel considered absolute effects over a five-year time-frame along with other contextual factors in suggesting the use of SGLT-2 inhibitors for adults at low and moderate risk of CKD progression and complications (weak recommendations) and recommending use for adults at high and very high risk (strong recommendations).

Conclusions: This guideline, part of the Rapid Recommendations series, provides novel risk-stratified recommendations for the use of SGLT-2 inhibitors for adults with CKD. Guidance is accompanied by interactive evidence summaries and decision aids.