The differential effects of ertugliflozin on glucosuria and natriuresis biomarkers: Prespecified analyses from VERTIS CV. Issue 6 (28th March 2022)

• Record Type: Journal Article
• Authors: Cherney, David Z. I.; Cosentino, Francesco; Pratley, Richard E.; Dagogo‐Jack, Samuel; Frederich, Robert; Maldonado, Mario; Liu, Jie; Pong, Annpey; Liu, Chih‐Chin; Cannon, Christopher P.
• Is Part Of: Diabetes, obesity & metabolism. Volume 24:Issue 6(2022)
• Page Start: 1114
• Page End: 1122
• Publication Date: 2022-03-28
• Subjects: cardiovascular disease -- diabetic nephropathy -- randomized trial -- SGLT2 inhibitor -- type 2 diabetes; Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.14677
• Languages: English
• ISSNs: 1462-8902

Abstract

Abstract: Aims: This prespecified exploratory analyses from VERTIS CV (NCT01986881) aimed to assess the effects of the sodium‐glucose cotransporter‐2 (SGLT2) inhibitor ertugliflozin on glucosuria‐related (glycated haemoglobin [HbA1c], uric acid, body weight) and natriuresis‐related (blood pressure, haemoglobin, haematocrit, serum albumin) biomarkers according to kidney function risk category. Materials and methods: Patients with type 2 diabetes and atherosclerotic cardiovascular disease were randomized to placebo, ertugliflozin 5 mg, or ertugliflozin 15 mg (1:1:1). Analyses compared placebo (n = 2747) versus ertugliflozin (pooled; n = 5499) on glucosuria‐ and natriuresis‐related biomarkers according to baseline estimated glomerular filtration rate (eGFR) subgroup and Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease (KDIGO CKD) risk category. Results: Patients were classified according to KDIGO CKD low‐ (49%), moderate‐ (32%) and high‐/very‐high‐risk categories (19%), and eGFR groups 1 (25%), 2 (53%) and 3 (19%). At Week 18, the high‐/very‐high‐risk category had a smaller placebo‐subtracted least squares mean (LSM) change from baseline (95% confidence interval) in HbA1c (−0.34 [−0.43, −0.25]) compared with the low‐ and moderate‐risk categories (−0.54 [−0.60, −0.49] and − 0.47 [−0.54, −0.40], respectively). This pattern was maintained throughout the study ( P interaction = 0.0001). Similar patterns based on baseline eGFR G stage were observed. Placebo‐subtracted LSM changes from baseline in uric acid were lowest in the high‐/very‐high‐risk category at Weeks 6 and 18, but the pattern was not maintained after Week 156 ( P interaction = 0.15). Effects of ertugliflozin on body weight and natriuresis‐related biomarkers did not differ across KDIGO CKD categories. Conclusions: In VERTIS CV, ertugliflozin was associated with physiologically favourable changes in glucosuria‐ and natriuresis‐related biomarkers. Glycaemic efficacy of ertugliflozin was attenuated in patients with higher chronic kidney disease (CKD) risk. Effects on other biomarkers were consistent, regardless of CKD risk stage.