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

Patient preference is key 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), randomised double-blind, three-way crossover trial patients received three different second or third line once-daily type 2 diabetes glucose-lowering drugs (pioglitazone 30mg, sitagliptin 100mg, and canagliflozin 100mg). As part of a prespecified secondary endpoint we examined patients’ drug preference after they had tried all 3 drugs. 448 participants were treated with all three drugs which overall showed similar glycaemic control (HbA1c on pioglitazone 59.5 sitagliptin 59.9, canagliflozin 60.5mmol/mol, p=0.19). 115 patients (25%) preferred pioglitazone, 158 (35%) sitagliptin, 175 (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 lower vs. non-preferred) and fewer side effects (mean 0.50[0.35, 0.64] fewer side effects vs. non-preferred). Allocating therapy based on 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% v 30%) and the fewest side effects (67% v 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 optimising treatment for type 2 diabetes.