Inhibitors of dipeptidyl peptidase 4 (DPP-4is) are a drug class used for the treatment of Type II Diabetes Mellitus (T2DM). The dose of most of the drugs of the class has to be adjusted according to the level of patients' kidney function. Linagliptin can be prescribed irrespective of kidney function as it is not excreted via the kidneys. Nevertheless, a recent UK study demonstrated that 42% of T2DM patients with moderate or severe renal impairment were initiated on a DPP-4i (except linagliptin) dose which was higher than the recommended dose in relation to their kidney function. The proposed study aims to explore a) whether T2DM patients with moderate or severe kidney impairment who are initiating on a higher than the recommended dose of a DPP-4i have their dose adjusted or switch to other, appropriate DPP-4i therapies for the level of kidney function during follow up visits to their GP, b) whether patients with no kidney impairment who initiate on an appropriate DPP-4i dose have their dose adjusted when their kidney function is reduced to levels requiring dose adjustment c) whether there are regional variations in inappropriate prescribing of DPP-4 inhibitors across the 13 CPRD defined regions. The findings of this study will aim to contribute to medical education informing GP prescribing decisions.
DPP-4i drug class is indicated for the glycaemic control in patients with T2DM. According to the Summary of Product Characteristics (SmPC), Saxagiptin, Sitagliptin, Alogliptin and Vildagliptin require dose adjustments for patients with certain level of impaired renal functionality. Linagliptin, being available in only one dose of 5mg, is the only drug of the class which does not require dose adjustments in relation to patients' renal function as is not excreted via the kidneys. A recent CPRD study, however, demonstrated that 42% of T2DM patients with moderate to severe renal impairment initiated on a DPP-4i (except linagliptin) were on a higher than the recommended dose for the level of their renal function. Adopting a retrospective cohort study design, the primary objective of this proposal is to examine patterns of dose adjustment and therapy switching occurring within DPP-4i class amongst T2DM patients with moderate or severe renal impairment initiating on a higher than the recommended DPP-4i dose for the level of their renal function, as well as among T2DM patients with no renal impairment who have subsequently their renal function reduced to levels where dose adjustment is required. Moreover, a secondary objective of this proposal is to provide insights about patterns of regional variation of inappropriate prescribing in the country based on a cross-section of data from the 13 UK regions available in CPRD. To address these objectives a number of analyses have been suggested. In the first analysis a cohort of T2DM patients with impaired renal function (expressed by an eGFR <60 ml/min/1.73 m2 or a clinical record indicating a stage 3/3a/3b/4/5 renal disease), who initiate on a high dose of a DPP-4i inhibitor will be followed up for at least 12 months and Kaplan Meier curves will be potted and descriptive statistics will be generated to describe dose adjustment and therapy switching in the cohort. High DPP-4i dose occurrence in this patient cohort will be also described on regional level according to the 13 CPRD UK defined regions. In addition, a cohort of T2DM patients with no evidence of renal impairment who initiate on a high dose of a DPP-4i but subsequently develop renal impairment will be characterised in terms of their post renal impairment DPP-4i prescription to assess the occurrence of dose adjustment/therapy switching.
Amongst patients with moderate or severe renal impairment initiating on a higher than the recommended DPP-4 inhibitor dose for the level of their renal function): Counts and percentage of patients who have their DPP-4 inhibitor dose adjusted or switch to another, appropriate DPP-4 inhibitor therapy overtime; (As above) KM curves (time to event) for dose adjustment/DPP-4 inhibitor therapy switching; Amongst patients with no renal impairment who initiate on the high dose of a DPP-4 inhibitor: Counts and percentage of patients who have their therapy changed or switched when their renal function is reduced to a level where therapy switch/dose adjustment is required; Counts and percentage of inappropriate prescribing of DPP-4 inhibitors in CPRD defined regions across the UK.
Kamlesh Khunti - Chief Investigator - University of Leicester
Dionysios Spanopoulos - Corresponding Applicant - Eli Lilly & Co - UK
Brendan Barrett - Collaborator - Boehringer-Ingelheim - UK
Chris D Poole - Collaborator - Digital Health Labs Limited
Toni Roman - Collaborator - Eli Lilly & Co - UK