The differential effects of ertugliflozin on glucosuria and natriuresis biomarkers: Prespecified analyses from VERTIS CV.

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 (Pinteraction  = 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 (Pinteraction  = 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.

• Authors: David Z I Cherney, Francesco Cosentino, Richard E Pratley, Samuel Dagogo-Jack, Robert Frederich, Mario Maldonado, Jie Liu, Annpey Pong, Chih-Chin Liu, Christopher P Cannon, VERTIS CV Investigators
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 24 Issue 6 Pg. 1114-1122 (06 2022) ISSN: 1463-1326 [Electronic] England
• PMID: 35233908 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 John Wiley & Sons Ltd.

Chemical References

• Biomarkers
• Bridged Bicyclo Compounds, Heterocyclic
• Glycated Hemoglobin A
• Hypoglycemic Agents
• Sodium-Glucose Transporter 2 Inhibitors
• Uric Acid
• ertugliflozin

Topics

• Biomarkers
• Body Weight
• Bridged Bicyclo Compounds, Heterocyclic
• Diabetes Mellitus, Type 2 (complications, drug therapy)
• Female
• Glycated Hemoglobin
• Glycosuria (chemically induced)
• Humans
• Hypoglycemic Agents (therapeutic use)
• Male
• Natriuresis
• Renal Insufficiency, Chronic (chemically induced, complications, drug therapy)
• Sodium-Glucose Transporter 2 Inhibitors (adverse effects)
• Uric Acid