Sodium glucose co-transporter-2 (SGLT 2) inhibitors, initially developed for the treatment of hyperglycaemia in type 2 diabetes, have been shown in large placebo-controlled randomized trials to be effective at reducing cardiovascular risk and risk of kidney disease progression in people with chronic kidney disease (CKD) irrespective of diabetes status, level of kidney function, or primary kidney diagnosis. SGLT 2 inhibitors have also been shown to be beneficial for people with diabetes at high cardiovascular risk and people with heart failure irrespective of left ventricular ejection fraction. This update to the 2021 guideline was necessary as two further important large trials reported in 2022: DELIVER, which investigated the use of the SGLT 2 inhibitor dapagliflozin in people with heart failure with preserved or mildly reduced ejection fraction, and EMPA-KIDNEY, which investigated the use of empagliflozin in people with chronic kidney disease, including people with and without diabetes and people with and without albuminuria. The results from these trials and meta-analysis of the totality of the evidence greatly expanded our understanding of the uses of SGLT 2 inhibitors and have increased the strength of evidence on which to make recommendations for use.
The guideline retains its previous modular format with individual sections considering evidence in people with and without diabetes separately. For this Executive Summary, however, we provide a simpler quick reference list of the types of individuals with CKD who are likely to benefit from SGLT 2 inhibitors.
We make grade 1 recommendations for use to slow kidney disease progression (or rate of kidney function decline) or to reduce cardiovascular risk. These include the following groups irrespective of diabetes status*:
- eGFR of 20-45 ml/min/1.73m2
- eGFR of >45 ml/min/1.73m2 & a urinary albumin-to-creatinine ratio (uACR) of ≥25 mg/mmol†
- Symptomatic heart failure, irrespective of ejection fraction
* excludes those with polycystic kidney disease, type 1 diabetes, or a kidney transplant;
† urinary protein-to-creatinine ratio of 35 mg/mmol can be considered equivalent.
We recommend initiating SGLT 2 inhibition in people with type 2 diabetes and established coronary disease (if eGFR ≥20 ml/min/1.73m2), and that SGLT 2 inhibition can be continued until the need for dialysis or kidney transplantation arises.
We make grade 2 recommendations to suggest/consider treating the following groups:
- eGFR <20 ml/min/1.73m2 to slow progression of kidney disease
- Type 2 diabetes, an eGFR 45-60 ml/min/1.73m2 and a uACR of <25 mg/mmol
We also provide a summary of current indications for use of SGLT 2 inhibitors in the UK. We do suggest the kidney and cardiovascular benefits increasingly resemble a class effect. To support implementation we provide a quick reference guide for implementation (Table 1, below), template patient information leaflets, and a full lay summary of the guideline.
We would like to thank the working group for all their contributions.