The widespread presence of heart and kidney (cardiorenal) diseases in patients with type 2 diabetes mellitus has led to a broader disease management goal of reducing adverse clinical complications and death in these patients. In a time of emerging treatment options for type 2 diabetes that may offer benefits to patients with cardiorenal disease, as well as pose risks based on the precise combination of heart and kidney conditions, there is an increasing need to understand the interactions between diabetes complications and the impact on the choice of medications used to treat these combinations of diseases in clinical practice. Work to date include clinical trial studies in patients with type 2 diabetes who already have established heart, kidney and blood vessels problems. The studies show diabetes therapies reduce the progression of diabetes complications. However, as only limited number of people can be enrolled in trial studies due to the rigorous selection criteria, the findings may not be generalised across all populations. The benefit of these therapies on diabetes complications have been demonstrated in real life clinical setting. However, the emerging role of these therapies in the people with type 2 diabetes who have no prior history of cardiorenal diseases is yet to be explored. Therefore, to provide answers to these specific questions, this study will use administrative healthcare records to compare the clinical and cost benefits of two classes of diabetes therapies in reducing the risk of cardiorenal diseases and death in type 2 diabetes patients.
It is increasingly being recognised there are commonalities between cardiovascular, renal and metabolic (CaReMe) diseases with clinical overlap between these diseases and their associated complications. Although these relationships between disorders are increasingly being elucidated there is often under-recognition by health care professionals and patients and this contributes to patients being managed for conditions in isolation. These relationships are increasingly important as therapies develop that could address multiple aspects of disease outcomes and may be used across this spectrum of disorders. Using a cohort of prevalent type 2 diabetes (T2D) patients, we will compare the risk of cardiovascular and renal disease outcomes between new users of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and new users of dipeptidyl peptidase-4 inhibitors (DPP-4i) in cardiorenal disease-free patients. We compare the patterns of cardiorenal disease manifestation over time, and their subsequent association with adverse clinical outcomes such as cardiovascular (CV) and all-cause mortality where feasible. This study will utilise the CPRD Aurum database and the study period will begin on 1 January 2007 and will end on 30 September 2019. Each of the clinical outcomes of interest will be described separately. Event rates and 95% CIs will be reported as both incidence risks and incidence rates. Survival distributions utilising Kaplan-Meir method will describe time to cardiorenal disease progression, time to CV- and all-cause mortality. Relative risks and risk factors associated with outcomes will be estimated using Cox proportional hazard models. In addition, we aim to further evaluate and compare the healthcare cost benefit of the cardiovascular and renal outcomes between new users of SGLT-2i and new users of DPP-4i. Such evidence will be used to highlight any unmet treatment needs and inform the current literature gap in this area.
The study outcomes are aligned to the core objectives of this study and described below.
Primary objective: Cardiovascular and renal outcomes between new users of SGLT-2i and new users DPP-4i
Primary outcomes include specific hospitalisations for heart failure (HF), myocardial infarction (MI), stroke, peripheral artery disease (PAD), renal outcomes (including hospitalisation for kidney disease and end-stage renal disease [ESRD]), CV- and all-cause death, and their associated risk factors.
Secondary objective: Health care cost of CV and renal disease after initiation of SGLT-2i and DPP-4i
Secondary outcomes include monetised costs of health care resource use; resources include disease management services in the clinical guideline, e.g., GP consultations, laboratory tests, medications and hospitalisations.
Jil Billy Mamza - Chief Investigator - AstraZeneca Ltd - UK Headquarters
Jil Billy Mamza - Corresponding Applicant - AstraZeneca Ltd - UK Headquarters
Amitava Banerjee - Collaborator - University College London ( UCL )
Betina Blak - Collaborator - AstraZeneca Ltd - UK Headquarters
George Godfrey - Collaborator - AstraZeneca Ltd - UK Headquarters
Iskandar Idris - Collaborator - University of Nottingham
Kamlesh Khunti - Collaborator - University of Leicester
Mike Ford - Collaborator - AstraZeneca Ltd - UK Headquarters
Ruiqi Zhang - Collaborator - AstraZeneca Ltd - UK Headquarters
Tamsin Morris - Collaborator - AstraZeneca Ltd - UK Headquarters
Una Rigney - Collaborator - AstraZeneca Ltd - UK Headquarters
HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation