Effective glycaemic control in type 2 diabetes reduces the risk of microvascular complications; however, healthcare professionals need to remember that there are risks to very tight glycaemic control, which are dependent on individual risk factors. Kidney disease is one such factor that can often limit the use of some anti-diabetes treatments. It is estimated that a third of people with type 2 diabetes have chronic kidney disease (CKD) in some stage of severity (Middleton et al, 2006). In a study using observed and modelled data from the UK, researchers measured the annual probability of transitioning through the stages of CKD, death and other long-term measures. The authors estimated that each year, people with microalbuminuria had a 2.8% chance of progressing to macroalbuminuria and a 3% risk of mortality. Those with macroalbuminuria had a 2.3% chance of progressing to elevated plasma creatinine or requiring renal replacement therapy, and a 4.6% risk of mortality. Those who received renal replacement therapy were estimated to have a death rate of 19.2% (Adler et al, 2003).
Dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists occupy a growing place in the armamentarium of treatments for the management of hyperglycaemia in type 2 diabetes, and renal function must be considered and monitored when these treatments are in use.
Most DPP-4 inhibitors (sitagliptin, vildagliptin, saxagliptin, alogliptin) undergo extensive renal clearance (Scheen, 2010). Therefore, in deteriorating renal function, the total exposure to these drugs is increased so dosage reductions are required. The DPP-4 inhibitor linagliptin is eliminated predominantly through the hepatobiliary route and renal excretion represents only a minor elimination pathway (Blech et al, 2010), so dose adjustments are not a requirement in CKD (Graefe-Mody et al, 2011).
In the case of the GLP-1 receptor agonist class, and according to their respective summary of product characteristics (SPCs), exenatide BID and QW are eliminated by renal mechanisms. It is not possible to measure creatinine clearance in primary care, so eGFR values are used as a surrogate in deciding when to stop exenatide BID and QW. The SPCs recommend caution in increasing the dose of exenatide BID if eGFR is 30–50 mL/min/1.73 m2 and that once-weekly versions should not be recommended if eGFR is <50 mL/min/1.73 m2 (electronic Medicines Consortium [eMC], 2016a; 2016b). No specific organ has been identified as the major route of elimination of liraglutide but it should be stopped if eGFR is <30 mL/min/1.73 m2 (eMC, 2016c). Only limited pharmacokinetic data are available for dulaglutide, lixisenatide and lixisenatide, so their use at eGFR <30 mL/min/1.73 m2 is not currently recommended.
Many individuals with type 2 diabetes and reduced renal function continue on full doses of incretin-based anti-diabetic medicines, despite their respective product licences. The aims of this audit are to assess the prevalence of inappropriate prescribing of incretin-based agents in people with renal impairment and explore how to reduce inappropriate prescribing.
Top tips for carrying out the audit from Jane Diggle, Practice Nurse, West Yorkshire:
- When searching, ensure you include the brand and generic names for the drugs, and include DPP-4 inhibitor/metformin combinations.
- Search in current medication only.
- If your lab has changed methods for calculating eGFR (e.g. MDRD, CKD-EPI) then these will have different codes – ensure you include both.
- Undertaking the eGFR search on your population with type 2 diabetes, then combining it with your search of those on each type of incretin therapy simplifies the data collection.
- You will then need to manually review the records of the small number of patients flagged up to ensure appropriate therapy changes have been made.
- Add an alert to the records of those who need dose or therapy changes as well as contacting them, so this can be undertaken opportunistically if they attend.
The instructions below explain how to complete the audit. You can download the full-size audit form at: www.diabetesandprimarycare.co.uk/audits to fill in and retain. The audit should take no more than a few hours to complete.
After you have completed the first data collection, you can send in your top-line aggregated data to
Instructions to complete the audit
- To assess the prevalence of inappropriate prescribing of incretin-based agents in people with type 2 diabetes and renal impairment.
- To explore how to reduce inappropriate prescribing of incretin-based agents in people with type 2 diabetes and renal impairment through appropriate local implementation strategies.
This will be a two-step audit completed in primary care centres in the UK. The first data collection will be done between 1st September and 31st October 2016 and follow-up data collection will be done 6 months later to allow for appropriate interventions to be put in place at the local or practice level in order to effect change.
- People with type 2 diabetes and a most recent estimated glomerular filtration rate (eGFR) <50 mL/min/1.73 m2 taking a dipeptidyl peptidase-4 (DPP-4) inhibitor should have a dosage review and dose modifications or drug stopped if appropriate.
- People with type 2 diabetes and a most recent eGFR <50 mL/min/1.73 m2 taking a glucagon-like peptide-1 (GLP-1) receptor agonist should have a dosage review and drug stopped if appropriate.
- For criterion 1, 70% of people with type 2 diabetes and reduced renal function (a most recent eGFR <50 mL/min/1.73 m2) should have had the doses of their DPP-4 inhibitor treatment modified or stopped if appropriate as per the product licence.
- For criterion 2, 70% people with type 2 diabetes and reduced renal function (a most recent eGFR <50 mL/min/1.73 m2) should have had their GLP-1 receptor agonist reviewed or stopped if appropriate as per the product licence.
A standard of 70% is selected as realistic as the authors of a recent audit noted that 30% of patients fitting the criteria did not have down titration of doses of DPP-4 inhibitors (Lee et al, 2016).
N.B. Set a reminder on the practice’s electronic calendar to repeat the audit 6 months later.
Download the full-size audit form at www.diabetesandprimarycare.co.uk/audits