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Extra-Glycaemic Indications of SGLT2 Inhibitors

Guidelines presents Primary Care Hacks, a series of clinical aide-memoires across a range of topics. Developed by Dr Kevin Fernando, Primary Care Hacks aim to provide a quick and easy resource for primary healthcare professionals and ultimately help improve patients' lives.

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Extra-Glycaemic Indications of SGLT2 Inhibitors

SGLT2 inhibitors are now the standard of care for the majority of people living with type 2 diabetes as preferred add-on therapy to metformin. SGLT2 inhibitors are now also being used in people without type 2 diabetes; however, currently available SGLT2 inhibitors have different licensed indications as well as estimated glomerular filtration rate (eGFR) thresholds for use. This makes life potentially confusing for primary healthcare professionals.

This Primary Care Hack summarises the extra-glycaemic indications of currently available SGLT2 inhibitors, to allow you to prescribe these drugs safely and appropriately in primary care.

Latest Updates

September 2023:

  • new recommendations were added regarding the continuation of empagliflozin in chronic kidney disease (CKD) stage 4–5 patients with symptomatic chronic heart failure (HF) regardless of ejection fraction (HFrEF and HF with preserved ejection fraction [HFpEF]) in adults with or without T2D already initiated with treatment
  • new indication and recommendation was added for treatment with empagliflozin in adult patients with CKD with or without CKD
  • indication for cardiovascular (CV) risk reduction as add-on to standard of care in adults with T2D and established CV disease was removed.
January 2023: 
  • update made to the treatment indication of dapagliflozin, from symptomatic chronic HF with HFrEF in adults with or without T2D, to symptomatic chronic HF regardless of ejection fraction (HFrEF and HFpEF) in adults with or without T2D, following a Medicines and Healthcare products Regulatory Agency licence extension for dapagliflozin in Great Britain in December 2022 for the treatment of symptomatic chronic HF. See the dapagliflozin summary of product characteristics for further details.

Expand the table for full view. Find a downloadable PDF of the table at the end of the article.

SGLT2IndicationCKD Stage (ml/min/1.73 m2)
  Stages G1 and G2 eGFR ≥60Stage G3a eGFR 45–49Stage G3b eGFR 30–44Stage G4 eGFR 15–30Stage G5 eGFR <15
CanagliflozinTreatment of diabetic kidney disease in adults with T2D as add-on to standard of careInitiate or continue 100 mgIf urinary ACR ≥30 mg/mmol, continue 100 mg and continue dosing until dialysis or renal transplantation

Do not initiate if eGFR <30

DapagliflozinTreatment of symptomatic chronic heart failure regardless of ejection fraction (HFrEF and HFpEF) in adults with or without T2DInitiate or continue 10 mgNo dose adjustment is required based on renal function

It is not recommended to initiate if eGFR <15

Treatment of CKD in adults with or without T2D
EmpagliflozinTreatment of symptomatic chronic heart failure regardless of ejection fraction (HFrEF and HFpEF) in adults with or without T2DInitiate or continue 10 mgContinue 10 mg in patients already started but due to limited experience, it is not recommended to initiate if eGFR <20
Treatment of CKD in adults with or without T2D
  • The glucose-lowering efficacy of all SGLT2 inhibitors is dependent on renal function and is reduced when eGFR <45 and likely in people with severe renal impairment. Therefore, if eGFR falls <45, additional glucose-lowering treatment should be considered in people living with T2D
  • SGLT2 inhibitors are not recommended for people living with T1D
  • NICE TA775 and SMC2428 advise initiation in people with eGFR 25–75 and T2S or ACR ≥22.6 mg/mmol (≥23 mg/mmol in SMC2428)
  • Table based on author's interpretation and summaries of product characteristics
  • At the time of publication, ertugliflozin has no extra-glycaemic indications.
ACR=albumin/creatinine ration; CKD=chronic kidney disease; eGFR=estimated glomerular filtration rate; HFpEF=heart failure with preserved injection fraction; HFrEF=heart failure with reduced ejection fraction; NICE TA=NICE technology appraisal; SGLT2=sodium–glucose cotransporter 2; SMC=Scottish Medicines Consortium; T1D=type 1 diabetes; T2D=type 2 diabetes.
Click on the link below for a downloadable PDF of the Primary Care Hack

Extra-Glycaemic Indication of SGLT2 Inhibitors

Primary Care Hacks are developed by Dr Kevin Fernando, GP Partner, North Berwick Health Centre; GP with special interest in CVRM and medical education; Content Advisor for WebMD Medscape Global and UK. This Primary Care Hack is based on the author's interpretation of relevant summaries of product characteristics. Primary Care Hacks are for information for primary healthcare professionals in the UK only. They bring together currently available recommendations and/or prescribing information and indications for therapeutics licensed within Great Britain. Licensed indications and/or prescribing information for Northern Ireland may differ. You are advised to review local licensed indications before prescribing any therapeutic. Primary Care Hacks are reviewed intermittently to ensure the information is up to date at the time of publication. Primary Care Hacks are independently produced by WebMD, LLC and have not been created in conjunction with any guideline or prescribing body.

Erratum, October 2023: An earlier version of this Primary Care Hack incorrectly stated dosing for dapagliflozin and empagliflozin at 100 mg. This has now been corrected to 10 mg.