Patients who develop oedema on initiating thiazolidinedione therapy have an improved glycaemic response: a MASTERMIND study

Special Issue: Abstracts of the Diabetes UK Professional Conference 2015, ExCeL London, 11–13 March 2015This is the author accepted manuscript. The final version is available from WileyBackground/aim: Oedema is a common and serious side effect ofthiazolidinedione therapy. A stratified medicine approach wouldaim to give thiazolidinediones to patients likely to have a goodglycaemic response but not to develop oedema. We investigatedwhether oedema was associated with glycaemic response tothiazolidinedione therapy.Methods: We studied 10,486 patients initiating a thiazolidinedionefrom Clinical Practice Research Datalink (CPRD), and identifiedmedical records of oedema in the subsequent 12 months. Responsewas defined as change in HbA1c at 12 months and was adjusted forbaseline HbA1c, baseline body mass index, gender and adherence(medication possession ratio). In secondary analyses we restrictedoedema classification to patients with concomitant weight gain. As acomparison the same analysis was performed in 13,089 patientsinitiating a sulfonylurea.Results: The 3% of patients with recorded oedema onthiazolidinediones had a mean (confidence interval) 3 (1.7–4.3)mmol/mol greater fall in HbA1c (p 3kg (p 8kg (p 3kg (p=0.19).Conclusion: Patients with Type 2 diabetes who develop oedemaon initiating thiazolidinediones have an improved glycaemicresponse, and more severe oedema is associated with greaterHbA1c reduction. This supports glycaemic lowering andfluid retention being mediated by a common pathway ofthiazolidinedione drug action

Patient preference for second- and third-line therapies in type 2 diabetes: a prespecified secondary endpoint of the TriMaster study

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this recordData availability: To minimize the risk of patient re-identification, de-identified individual patient-level clinical data are available under restricted access. Requests for access to anonymized individual participant data (IPD) and study documents should be made to the corresponding author and will be reviewed by the Peninsula Research Bank Steering Committee. Access to data through the Peninsula Research Bank will be granted for requests with scientifically valid questions by academic teams with the necessary skills appropriate for the research. Data that can be shared will be released with the relevant transfer agreement.Code availability: Requests for access to code should be made to the corresponding author and will be reviewed by the Peninsula Research Bank Steering Committee. Access to code through the Peninsula Research Bank will be granted for requests with scientifically valid questions by academic teams with the necessary skills appropriate for the research. Code will be released by the lead statistician.Patient preference is very important for medication selection in chronic medical conditions, like type 2 diabetes, where there are many different drugs available. Patient preference balances potential efficacy with potential side effects. As both aspects of drug response can vary markedly between individuals, this decision could be informed by the patient personally experiencing the alternative medications, as occurs in a crossover trial. In the TriMaster (NCT02653209, ISRCTN12039221), randomized double-blind, three-way crossover trial patients received three different second- or third-line once-daily type 2 diabetes glucose-lowering drugs (pioglitazone 30 mg, sitagliptin 100 mg and canagliflozin 100 mg). As part of a prespecified secondary endpoint, we examined patients' drug preference after they had tried all three drugs. In total, 448 participants were treated with all three drugs which overall showed similar glycemic control (HbA1c on pioglitazone 59.5 sitagliptin 59.9, canagliflozin 60.5 mmol mol-1, P = 0.19). In total, 115 patients (25%) preferred pioglitazone, 158 patients (35%) sitagliptin and 175 patients (38%) canagliflozin. The drug preferred by individual patients was associated with a lower HbA1c (mean: 4.6; 95% CI: 3.9, 5.3) mmol mol-1 lower versus nonpreferred) and fewer side effects (mean: 0.50; 95% CI: 0.35, 0.64) fewer side effects versus nonpreferred). Allocating therapy based on the individually preferred drugs, rather than allocating all patients the overall most preferred drug (canagliflozin), would result in more patients achieving the lowest HbA1c for them (70% versus 30%) and the fewest side effects (67% versus 50%). When precision approaches do not predict a clear optimal therapy for an individual, allowing patients to try potential suitable medications before they choose long-term therapy could be a practical alternative to optimizing treatment for type 2 diabetes.Medical Research Council (MRC)National Institute for Health and Care Research (NIHR