| Outcome Measures: |
Primary: On treatment HbA1c in obese patients (BMI >30kgm-2), compared to non-obese patients, Outcome measure will test hypothesis that patients with insulin resistance, characterised clinically by a raised BMI (\>30 kg/m2), compared to non-obese patients, will: 1. Respond well to pioglitazone, a thiazolidinedione that works as an insulin sensitiser. 2. Respond less well to sitagliptin, a DPP4i, which works through stimulating endogenous insulin secretion post-prandially., 16 weeks|On treatment HbA1c in patients with an eGFR <90 mls/min/1.73m2 compared to patients with an eGFR >90 mls/min/1.73m2., Outcome measure will test hypothesis that patients with modestly reduced estimated glomerular filtration rate (eGFR 60-90 mls/min/1.73m2), compared to those with eGFR \>90 mls/min/1.73m2, will: 1. Respond poorly to canagliflozin, a SGLT2 inhibitor, which works through inhibiting the active reabsorption of glucose in the proximal tubule, as the reduced eGFR will reduce the glucose-lowering efficacy. 2. Respond well to sitagliptin, a DPP4i that is renally cleared, as the reduced eGFR will increase plasma DPP4i concentrations., 16 weeks | Secondary: Patient preference, Patient treatment preference of study drug within hypothesised strata and overall, 48-54 weeks (3 x 16 weeks of therapy)|Prevalence of side effects, Prevalence of side effects within hypothesised strata and for specific drugs, to include: weight gain, hypoglycaemia, oedema, genital tract infection and discontinuation of therapy, 48-54 weeks (3 x 16 weeks of therapy)|HbA1c on therapy against predefined test of gender heterogeneity, Predefined test of gender heterogeneity with pilot data suggesting females are likely to show an improved response relative to males for pioglitazone., 16 weeks
|