Type 2 Diabetes Mellitus (T2DM) often causes kidney function decline; kidney function should be taken into consideration when treatment decisions for T2DM patients are to be made. DPP-4 inhibitors are a drug class used for managing T2DM, offering more flexibility in patients with kidney function decline. Still however, most members of the class require dose adjustment depending on patients' kidney function. The only exception is linagliptin which is licenced for all levels of kidney function. Previous studies have demonstrated that T2DM patients treated with DPP-4 inhibitors can be prescribed lower or higher doses in relation to kidney function specifications defined by the manufacturers. At the time, kidney function specifications were defined in Creatinine Clearance (CrCl) for all non-linagliptin DPP-4 inhibitors. Recently, manufacturer dosing specifications in relation to kidney function have changed for two members of the class. In particular, in January 2018 and July 2018, kidney function specifications for dose adjustment for sitagliptin and saxagliptin changed from CrCl to glomerular filtration rate (GFR) which is the recommended kidney function measure in the UK clinical practice. The aim of the study is to examine dose selection in relation to the new kidney function specifications.
The rationale of the study is to explore whether or not and the extent to which adoption of the recommended measure of kidney function into product specifications has resulted in an improvement in dose selection in routine clinical practice.
DPP-4 inhibitors (alogliptin, linagliptin, saxagliptin, sitagliptin, vildagliptin) are a drug class indicated for the glycaemic control in patients with Type II Diabetes Mellitus (T2DM). Summaries of Product Characteristics (SPC) require all DPP-4 inhibitors, except linagliptin, to be dose adjusted according to renal function. Linagliptin is the only member that can be prescribed irrespective of patient renal function. Previous UK study demonstrated that approximately one third of T2DM patients initiating alogliptin, saxagliptin, sitagliptin or vildagliptin with a Creatinine Clearance (CrCl) <50 mL/min, which was the common threshold of dose adjustment for all non-linagliptin DPP-4 inhibitors at the time of analysis, were on a higher dose than the SPC specified dose. In addition, another recent study demonstrated that at least 10% of T2DM patients with CrCl >50 mL/min initiating on a DPP-4 inhibitor were prescribed a lower than the SPC specified dose. In January and July 2018, SPCs of sitagliptin and saxagliptin were updated to include new requirements for dose adjustment, specifying an eGFR of 45 ml/min as new threshold for dose adjustment. Even though CrCl was the mainstay of measuring renal function in the past, currently, the recommended metric of renal function is glomerular filtration rate (GFR) in the UK clinical practice.
Adopting a retrospective cross-sectional study design and incorporating the new thresholds of dose adjustment for sitagliptin and saxagliptin, this study will generate descriptive statistics to to characterise DPP-4 inhibitor dose selection in relation to manufacturer specifications in a patient cohort treated with DPP-4 inhibitors after the implementation of renal threshold changesThe rationale of the study is to explore whether or not and the extent to which adoption of the recommended measure of kidney function into product specifications has resulted in an improvement in dose selection in routine clinical practice.
1. Higher than SPC specified dose per renal function range:
Alogliptin
o CrCl ( 50-30 ml/min): alogliptin 25 mg (n, %)
o CrCl (<30 ml/min): alogliptin 12.5 or 25 mg(n, %)
Vildagliptin
o CrCl ( < 50 ml/min): vildagliptin 50 mg BID (n, %)
Sitagliptin
o eGFR (< 45 30 ml/min): sitagliptin 100 mg (n, %)
o eGFR (<30 ml/min): sitagliptin 100 or 50 mg (n, %)
Saxagliptin
o eGFR (< 45 ml/min): saxagliptin 5 mg (n, %)
2. Lower than SPC specified dose per renal function range:
Alogliptin
o CrCl (> 50 ml/min): alogliptin 12.5 or 6.25 mg (n, %)
o CrCl (< 50-30 ml/min): alogliptin 6.25 mg (n, %)
Vildagliptin
o CrCl (> 50 ml/min): vildagliptin 50 mg QD (n, %)
Sitagliptin
o eGFR (> 45 ml/min): sitagliptin 50 or 25 mg (n, %)
o eGFR (< 45-30 ml/min): sitagliptin 25 mg (n, %)
Saxagliptin
o eGFR (> 45 ml/min): saxagliptin 2.5 mg (n, %)
Dionysios Spanopoulos - Chief Investigator - Eli Lilly & Co - UK
Dionysios Spanopoulos - Corresponding Applicant - Eli Lilly & Co - UK
Brendan Barrett - Collaborator - Boehringer-Ingelheim - UK
Joanne Webb - Collaborator - Eli Lilly & Co Ltd - US Headquarters
Michael Busse - Collaborator - Boehringer-Ingelheim - UK