Format

Send to

Choose Destination
Diabetes Care. 2019 Feb;42(2):318-326. doi: 10.2337/dc18-1871. Epub 2018 Dec 6.

Reduction of Cardiovascular Risk and Improved Estimated Glomerular Filtration Rate by SGLT2 Inhibitors, Including Dapagliflozin, Is Consistent Across the Class: An Analysis of the Placebo Arm of EXSCEL.

Author information

1
Quantitative Clinical Pharmacology, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Gaithersburg, MD lindsay.clegg1@astrazeneca.com.
2
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
3
Quantitative Clinical Pharmacology, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Waltham, MA.
4
Quantitative Clinical Pharmacology, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Gaithersburg, MD.
5
AstraZeneca, Cambridge, U.K.
6
Statisticon AB, Uppsala, Sweden.
7
Duke University and Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
8
Diabetes Trials Unit, University of Oxford, Oxford, U.K.

Abstract

OBJECTIVE:

The sodium-glucose cotransporter 2 inhibitors (SGLT2i) empagliflozin and canagliflozin reduce the incidence of major adverse cardiovascular events (MACE), all-cause mortality (ACM), and renal events in cardiovascular outcomes trials, with observational real-world evidence suggesting class effect benefits that include dapagliflozin. We examined the placebo arm of the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) to determine whether the effects of drop-in open-label dapagliflozin on MACE, ACM, and estimated glomerular filtration rate (eGFR) were consistent with the SGLT2i class as a whole.

RESEARCH DESIGN AND METHODS:

SGLT2i drop-in therapy occurred in 10.6% of EXSCEL participants, with 5.2% taking dapagliflozin. Propensity-matched cohorts of SGLT2i users and nonusers (n = 709 per group) were generated on the basis of their characteristics before open-label SGLT2i drop-in or at baseline for participants taking SGLT2i at enrollment and an equivalent study visit for non-SGLT2i users. Time to first adjudicated MACE and ACM was analyzed using Cox regression. eGFR slopes were compared between matched cohorts using a mixed-model repeated-measures analysis.

RESULTS:

In adjusted analyses, SGLT2i users (compared with nonusers) had a numerically lower risk of MACE (adjusted hazard ratio 0.79 [95% CI 0.49-1.28]), as did dapagliflozin users (0.55 [0.26-1.15]). SGLT2i users had a significantly lower ACM risk (0.51 [0.27-0.95]; dapagliflozin: 0.66 [0.25-1.72]). Compared with nonusers, eGFR slope was significantly better for SGLT2i users overall (+1.78 [95% CI 0.87-2.69] mL/min/1.73 m2 per year) and for dapagliflozin users (+2.28 [1.01-3.54] mL/min/1.73 m2 per year).

CONCLUSIONS:

This post hoc analysis of the placebo arm of EXSCEL supports a beneficial class effect for all SGLT2i, including dapagliflozin, for reduced ACM and less eGFR decline.

PMID:
30523029
DOI:
10.2337/dc18-1871
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center