Predictors of responders to non-responders with DPP-IV inhibitor and association between oral antidiabetic use with hypoglycaemia and cardiovascular outcome

Supervisors: Dr Iskandar Idris & Professor Richard Donnelly

Applications are invited from highly motivated individuals for the above studentship, based at the School of Graduate Entry Medicine and Health at the Royal Derby Hospital.

Dipeptidyl peptidase IV (DPP-IV) inhibitor is a novel glucose lowering agent increasingly used in the United Kingdom for the management of hyperglycaemia in patients with type 2 diabetes. Evidence from clinical trials suggest that this class of drugs may offer advantage over other oral glucose lowering therapy due to reduced risks of hypoglycaemia and neutrality effect on patients body weight. Guidelines from the National Institute of Clinical Excellence (NICE) have recommended for DPP-IV inhibitor to be considered as a second or third line drug for patients with type 2 diabetes, particularly where there are concerns about patients risk of weight gain or hypoglycaemia.

Despite this, the uptake of DPP-IV inhibitor in the UK is patchy. This is possibly due to the ongoing uncertainties of the clinical benefits of DPP-IV inhibitor in real world clinical practice as well as its place amongst other more established oral glucose lowering therapies. Evidence from meta-analysis of DPP-IV inhibitor suggests that low baseline HbA1c is the best predictor for achievement of A1c target whilst experimental data has shown DPP-IV inhibitor preserves beta cell mass and function. We would therefore postulate that DPP-IV inhibitor is most affective when introduced early during the course of diabetes. Furthermore, UK ‘real world’ data on the risks of hypoglycaemia between different oral glucose lowering agent which incorporate DPP-IV inhibitor usage is not available. The latter is particularly important given the recent debates about the risks of cardiovascular events in patients with increased risks of hypoglycaemia or with very low HbA1c values. Since diabetes is a progressive disease, combination therapy is widely used to achieve optimal glucose levels. Consequently, studies to investigate the role of individual glucose lowering therapies on their risk of developing CVD events are fraught with significant confounders and treatment bias. Furthermore, such studies do not reflect ‘real world’ medicine where dual, triple or quadruple therapies are often used with or without insulin to achieve target glucose levels.

Utilising data from a well- validated UK primary care electronic database will enable us to gain new insights into the CVD outcomes for different combination glucose lowering therapies, their appropriate place in the guidelines for managing hyperglycaemia in patients with type 2 diabetes as well as the association between oral antidiabetic drugs (OAD), risks of hypoglycaemia, Hba1c levels and adverse cardiovascular outcomes. The major difficulty for observational studies to provide reliable information on cardiovascular events however relates to the ability of primary care research database to balance measured and unmeasured confounders due to not having rigorous inclusion, exclusion criteria and exposure definitions. Several well documented examples exist where results from observational studies were reported to be misleading. To overcome this, we will use a recently validated method enhance the validity of the results.

Students should have, or will expect to attain at least a masters or a degree in either public health, epidemiology or health related sciences. In addition the candidate should have a good understanding of statistics, mathematics or computer science. This studentship is available for a period of 3 years and provides a stipend of £13,590 per annum. Due to funding restrictions this studentship is available to UK/EU citizens only. Non UK/EU citizens are welcome to apply but the grant will not cover the additional international fees.

For further information or for any questions, please contact Dr Iskandar Idris, Iskandar.Idris@nottingham.ac.uk. Please note that applications sent directly to this Email addresses will not be accepted.

Application forms are available from Mrs S Rougeolle, School of Graduate Entry Medicine & Health, University of Nottingham, Royal Derby Hospital, Uttoxeter Road, Derby, DE22 3DT. Tel: 01332 724618. Email: sue.rougeolle@nottingham.ac.uk.

Reference : MED1126
Closing Date : 30 November 2012

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Disclaimer: Every effort has been made to ensure the above information is current and correct. However, applicants should contact the appropriate administering body before making an application, as details do change frequently.