Introduction
heterogeneous disease, actionIn, diabetes
INSULIN RESISTANCE, TYPE 2 DIABETES, PATHOPHYSIOLOGY, DIABETES
Precision medicine aims to treat an individual based on their clinical characteristics. A differential drug response, critical to using these features for therapy selection, has never been examined directly in type 2 diabetes. We tested two hypotheses: 1) individuals with BMI>30kg/mPrecision medicine aims to tailor treatment to an individual based on their clinical characteristicsType 2 diabetes is an attractive candidate for a precision medicine approach as it is a heterogeneous disease with varying underlying pathophysiology, and there are many different options for glucose-lowering treatment available which have differing mechanisms of actionIn the 2022 ADA/EASD international guidelines, the targeting of therapy based on a person’s clinical features is limitedSimple clinical features, such as a person’s sex, surrogate markers of insulin resistance such as BMI and triglycerides, or markers of renal function such as estimated glomerular filtration rate (eGFR), can be used to stratify people with type 2 diabetes into subgroups showing differential responses to glucose lowering therapiesThe precision medicine approach to using these data-derived strata needs to be tested in a clinical trial. To date, there have been no trials directly examining a precision medicine approach to prescribing in type 2 diabetes. The effectiveness of any stratified approach for choosing between therapies will depend upon the extent to which differential responses can be predicted, and therefore the true test of a precision medicine approach would be to assess the within-person differential responses to therapy.We have carried out a three-drug, three-period, randomised crossover trial to assess two specific hypotheses (Individuals with a BMI >30kg/mIndividuals with an eGFR 60-90mls/min/1.73m