Renal Outcomes with DPP-4 Inhibitors Compared with Sulfonylurea as Add-on to Metformin among Patients with Type 2 Diabetes Mellitus in the UK

Date of Approval
Application Number
16_171
Technical Summary

The proposed study will assess the comparative effectiveness of using DPP-4 inhibitors vs. SU in addition to metformin in 2007-2014 in terms of incidence of renal outcomes (albuminuria, doubling of serum creatinine, changes in estimated glomerular filtration rate) among T2DM patients with more than 3 months of metformin alone in the UK. In addition, the study aims to describe the characteristics of patients receiving DPP-4 inhibitors vs. SU after more than 3 months of metformin therapy, with the earliest indications of simultaneous use of background metformin and either DPP-4 inhibitor or SU considered as the index date. Baseline covariates will be descriptively compared between the two cohorts using chi-squared tests for proportions and Wilcoxon rank-sum tests for continuous measures. Outcomes will be assessed during at least 12 months after the index date. Time to first occurrence of the outcomes of interest will be described using Kaplan-Meier survival analyses and log-rank p-values. Multivariate Cox proportional hazard models will be used to assess the differences in incidence rates adjusting for baseline differences in demographics (e.g., age, gender), clinical attributes (e.g., renal function, glycemic burden), comorbidities, and other medication use. Sensitivity analyses will estimate K-M curves and Cox models for propensity-score matched cohorts with similar baseline characteristics.

Health Outcomes to be Measured

Primary outcome: Incident microalbuminuria Other outcomes: Change in baseline category of albuminuria Change in serum creatinine level from baseline Stages of kidney disease as assessed using eGFR.

Collaborators

Noam Kirson - Chief Investigator - Analysis Group, Inc.
Urvi Desai - Corresponding Applicant - Analysis Group, Inc.
Christopher Edmonds - Collaborator - Astra Zeneca Inc - USA
Hung Heong Teh - Collaborator - Astra Zeneca Inc - USA
Jayanti Mukherjee - Collaborator - Bristol-Myers Squibb - USA ( BMS )
Kamlesh Khunti - Collaborator - University of Leicester
Katherine Tsai - Collaborator - MedImmune
Mark Meiselbach - Collaborator - Analysis Group, Inc.
Michael Hellstern - Collaborator - Analysis Group, Inc.
Phillip Hunt - Collaborator - Astra Zeneca Inc - USA
Zitong (Bruce) Jia - Collaborator - Analysis Group, Inc.