SGLT2 inhibitors and kidney outcomes in the real world

Dear Editor,

Sodium glucose cotransporter 2 (SGLT2) inhibitors have established efficacy for glucose lowering in routine clinical practice with recent RCT data confirming clear benefits for chronic kidney disease (CKD), as well as for heart failure, as highlighted in BMJ editorial (1).

However, the benefits from the trials on kidney disease may be slow to be realised in the UK, as the current guideline for use of SGLT2 inhibitors is only included as part of NICE (2) and SIGN (3) treatment algorithms for the management of type 2 diabetes. The NICE guideline for initiation of SGLT2 inhibitor therapy is based upon thresholds of glycaemia (HbA1c), without the inclusion of CKD as a treatment trigger for drug choice, as seen in the EASD/ADA guidelines (4)

Additionally, the SmPC/ current licence for each SGLT2 inhibitor has glomerular filtration rate [GFR] > 60 mL/min/1.73m2 for initiation, and discontinuation if GFR <45 mL/min/1.73m2. The lower threshold for discontinuation was further reinforced from early evidence of the reduced glucose lowering effect at lower levels of renal function (5).

In a recent database assessment of SGLT2 inhibitor prescribing in the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care network covering a population of >5 million people, a lower eGFR reflecting CKD was an exclusion for widespread prescribing. From the 26,700 SGLT2 inhibitor prescriptions, an eGFR <60 accounted for only 1.7% of prescriptions, while an eGFR ≥ 60 was observed in 93.2%. This finding is in keeping with current prescribing licence and NICE Guideline recommendations, but would potentially limit the utility of this drug class in reducing benefits for those with diabetes and coexistent CKD. The data do highlight that primary care is adhering to both NICE guidance for type 2 diabetes and the prescribing licence for this class of drugs.

It is indeed timely, that the UK rapidly adopt best practice for use of the class of drugs in keeping with other international guidelines and informed by the newer RCTs. With the usual precautions of osmotic side-effects and DKA risk, then perhaps the new mantra for Type 2 diabetes should be “prescribe SGLT2 inhibitors, protect kidneys and save lives”.

Michael Feher1, Neil Munro2, William Hinton1, Martin Whyte2, Simon de Lusignan1,2

1 Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
2 Department of Clinical and Experimental Medicine, University of Surrey, Guildford, UK

References

1. BMJ 2020;369:m1584
2. NICE Technology appraisal guidance [TA390], Canagliflozin, dapagliflozin and empagliflozin as monotherapies for treating type 2 diabetes. 2015
3. SIGN guidelines for Type 2 diabetes. https://www.sign.ac.uk/assets/sign154.pdf
4. Melanie J. Davies,David A. D’Alessio , Judith Fradkin, Walter N. Kernan , Chantal Mathieu, Geltrude Mingrone , Peter Rossing, Apostolos Tsapas, Deborah J. Wexler, John B. Buse. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. https://doi.org/10.1007/s00125-018-4729-5
5. Kohan DE, Fioretto P, Tang W. et al. Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control. Kidney Int 2014; 85: 962–971