Ertugliflozin offers some kidney protection

Despite earlier reports that the sodium-glucose transport protein 2 (SGLT2) inhibitor ertugliflozin did not live up to expectations for kidney disease outcomes, an analysis by Prof. David Cherney (University of Toronto, Canada) provides evidence that kidney disease outcomes with ertugliflozin were similar to those seen with other SGLT2 inhibitors.

The VERTIS CV study (NCT01986881) compared the SGLT2 inhibitor ertugliflozin (n=5,499) with placebo (n=2,747). The primary endpoint was a composite of kidney outcomes, including renal death, need for dialysis or transplant, or a doubling of serum creatinine reflecting a drop of at least 50% in estimated glomerular filtration rate (eGFR). Although the composite outcome showed a trend towards significant benefit, there was only a nominal 19% reduction of primary outcome events with ertugliflozin (HR 0.81; 95.8% CI 0.63-1.04; P=0.08) [1].

At the EASD 2020, Prof. Cherney presented several exploratory analyses [2], which were published in the journal Circulation [3]. He pointed out that applying a lower threshold for serum creatinine resulted in a sustained 40% or greater reduction in eGFR instead of a sustained doubling of serum creatinine, with consequent reductions in chronic kidney dialysis, transplant, or renal death. Adding this threshold in a post-hoc analysis showed a clinical benefit reaching statistical significance for the patients receiving ertugliflozin (HR 0.66; 95% CI 0.50-0.88; P<0.01). “This is in line with what has been observed with the other 3 SGLT2 inhibitor drugs”, Prof. Cherney said. He concluded that the results of the VERTIS CV trial provided evidence supporting the beneficial effects of this class of SGLT2 inhibitor on cardiovascular and renal outcomes. Ertugliflozin reduced the risk of the exploratory composite renal outcome of a sustained 40% decline in eGFR, chronic renal replacement therapy, or renal death. The relative risk reduction for the kidney composite was similar across all stages of chronic kidney disease (CKD), level of urine albumin-to-creatinine ratio (UACR), and type of kidney disease: improving global outcomes (KDIGO)-CKD risk category regardless of how CKD was defined. Ertugliflozin significantly reduced UACR in patients with albuminuria at baseline and preserved kidney function, especially in patients with microalbuminuria who are at greatest risk for CKD progression. Unfortunately, the routine use of UACR testing in patients with diabetes in general practice remains low, and UACR testing is also not part of standard care in cardiology practice. The eGFR declined acutely with ertugliflozin and the reduction was sustained over time when compared with placebo.

1. Pratley RE, et al. Results of the eValuation of ERTugliflozinEffIcacy and Safety CardioVascular Outcomes Trial (VERTIS-CV). ADA 2020.
2. Cherney DZ. Late-breaking presentation on renal outcomes. EASD 2020. Session: VERTIS CV outcome.
3. Cherney DZI, et al. Circulation. 2020 Nov 13.