Renal disease is a common complication of type 2 diabetes (T2DM) that affects one in three patients. In fact, the global rise in the incidence of end-stage renal disease, dialysis, and renal transplantations can be attributed primarily to the increasing prevalence of T2DM. The co-occurrence of T2DM and chronic kidney disease (CKD) is associated with greater insulin resistance, progression of T2DM, and an increased risk of developing cardiovascular disease (CVD). Furthermore, the therapeutic management of patients with T2DM is complicated by CKD, as renal impairment also decreases the clearance of most glucose-lowering medications – predisposing patients to drug-related toxicities, particularly low blood sugar. The recent publication of landmark clinical trials has shown that certain glucose lowering agents – such as sodium/glucose cotransporter-2 inhibitors (SGLT2i) and glucagon like peptide 1 receptor agonists (GLP-1RA) reduce the incidence of adverse kidney outcomes. However, it is currently unclear whether these benefits observed in certain high-risk populations in clinical trials are also evident among patients in the real world. The overall purpose of this study is to examine the comparative effectiveness of select second line glucose lowering therapies in preserving kidney function among patients with type 2 diabetes.
Renal disease is a common complication of type 2 diabetes (T2DM) affecting one in three patients. In fact, the global rise in the incidence of end-stage renal disease, dialysis, and renal transplantations can be attributed primarily to the increasing prevalence of T2DM. The co-occurrence of T2DM and chronic kidney disease augurs a long-term clinical course characterized by greater insulin resistance, accelerated progression of T2DM, and an increased risk of developing cardiovascular disease (CVD). The recent publication of landmark clinical trials has shown that certain glucose lowering agents – such as sodium/glucose cotransporter-2 inhibitors (SGLT2i) and glucagon like peptide 1 receptor agonists (GLP-1RA) reduce the incidence of adverse renal events. However, it is currently unclear whether these benefits observed in certain high-risk populations (e.g. established cardiovascular disease) in clinical trials are also evident among patients in the real world.
Thus, the overall purpose of this study is to examine the comparative effectiveness of SGLT2i (exposure) compared to non-SGLT2i second-line glucose lowering therapies (control group) in preserving renal function among patients with type 2 diabetes. To achieve this objective, we will conduct a retrospective, population-based cohort study using CPRD Gold data to generate a cohort of patients initiating the medications of interest. Thereafter, we will employ a 1:1 nearest neighbour propensity score matching approach to adjust for relevant confounders, and Cox proportional hazard models to estimate adjusted hazard ratios for the outcomes of interest. The primary outcome of interest is defined as a 30% reduction in renal function from its baseline value. Successful competition of this study will generate robust and timely data on the renal effectiveness of second-line glucose lowering therapies, allowing patients and clinicians to make more informed evidence-based healthcare decisions.
Reduction in kidney function by 30% of its baseline value (primary endpoint); reduction in kidney function by 40%, 50% and 57% of its baseline value (secondary endpoints).
Chintan Dave - Chief Investigator - Rutgers, The State University of New Jersey
Julia Liaw - Corresponding Applicant - Rutgers, The State University of New Jersey
Abner Nyandege - Collaborator - Rutgers, The State University of New Jersey