NICE recommends SGLT2 inhibitors for chronic kidney disease

For adults with type II diabetes and CKD who are taking an angiotensin receptor blocker (ARB) or an ACE inhibitor, NICE says an SGLT2 inhibitor should be offered in addition if the albumin-to-creatinine ratio (ACR) is over 30mg/mmol and the patient meets the criteria in the SGLT2 inhibitor's marketing authorisation.

For adults with an ACR between 3 and 30mg/mmol, an SGLT2 inhibitor should be considered in addition to the ARB or ACE inhibitor if the patient meets the criteria in the SGLT2 inhibitor's marketing authorisation.

Cost benefit

NICE said 'strong evidence' from 'well-conducted randomised controlled trials' showed that SGLT2 inhibitors reduced the risk of chronic kidney disease progression, mortality and cardiovascular events in adults with type II diabetes and chronic kidney disease.

Economic modelling for people with an ACR above 30mg/mmol at baseline showed that SGLT2 inhibitors were likely to be both more effective and cost saving in this group than standard treatment, said NICE.

The guideline committee made a different recommendation for patients with a baseline ACR of 3 to 30mg/mmol, as it said these people 'will experience fewer cardiovascular events and events relating to CKD than people with a higher ACR' so there is 'more uncertainty' around the clinical and cost effectiveness in this group. 

Reduced mortality

Canagliflozin (Invokana) and dapagliflozin (Forxiga) are currently the only SGLT2 inhibitors licensed for the treatment of diabetic kidney disease. 

The randomised double-blind CREDENCE trial evaluated canagliflozin versus placebo in 4401 patients with type II diabetes who had an eGFR of 30 to <90ml/min/1.73m² and albuminuria (urinary ACR >300 to 5000mg/g). Participants received standard therapy for diabetic kidney disease in the form of a maximum tolerated dose of an ACE inhibitor or ARB, in addition to canagliflozin 100mg daily or placebo.

Compared with patients who received placebo, those treated with canagliflozin experienced a 30% reduction in the risk of the primary composite endpoint, comprising end-stage renal disease, doubling of serum creatinine and renal or cardiovascular death, with event rates of 43.2 versus 61.2 per 1000 patient-years (hazard ratio [HR] 0.70; 95% CI 0.59–0.82; p=0.00001).

The double-blind DAPA-CKD trial randomised 4304 patients with CKD stages 2–4 and albuminuria, with and without type II diabetes, to receive dapagliflozin 10mg or placebo once daily. Participants also received standard of care, which included an ACE inhibitor or an ARB. The primary composite endpoint was worsening of renal function or risk of death (defined as a composite of an eGFR decline ≥50%, onset of end-stage renal disease or death from cardiovascular or renal cause).

Over a median of 2.4 years, dapagliflozin, in addition to standard of care, significantly reduced the relative risk of the composite primary endpoint by 39% compared with placebo (hazard ratio 0.61; 95% CI 0.51–0.72, p<0.001).

Dose adjustment

The updated NICE guidance highlights that patients treated with SGLT2 inhibitors must meet the criteria in the drugs' marketing authorisations, including relevant estimated glomerular filtration rate (eGFR) thresholds. A quick guide to these thresholds can be found in the MIMS table of dose adjustments for antidiabetic agents in renal impairment.