Primary analysis
SENSITIVITY
The five components of the estimand for both hypotheses are shown in For hypothesis 1 (BMI dependent differential glycaemic responses to pioglitazone and sitagliptin), 356 (68% of randomised participants) had valid HbA1c values for both pioglitazone and sitagliptin and so were eligible for hypothesis 1 primary analysis (BMI strata). Eligible participants were slightly older and had a slightly lower HbA1c at baseline, compared with those without valid HbA1c values, but were similar with respect to other characteristics (Participants with BMI <=30kg/mA tipping point analysis suggested the missing data would need to show a 3.1mmol/mol difference in HbA1c in the opposite direction to the trial results to change the statistical significance of the findings.The association between BMI and difference in response between pioglitazone and sitagliptin was linear on a continuous scale indicating that there would be an even greater benefit for pioglitazone at higher BMIs and greater benefit for sitagliptin at lower BMIs (For hypothesis 2 (eGFR and differential responses to sitagliptin and canagliflozin), 342 (65% of randomised participants) had valid HbA1c values for both sitagliptin and canagliflozin, and so were eligible for primary analysis for hypothesis 2 (eGFR strata). There were no differences in characteristics between those eligible and ineligible for hypothesis 2 analysis (Participants with an eGFR 60-90mls/min/1.73mA tipping point analysis suggested the missing data would need to show a 3.2mmol/mol difference in HbA1c in the opposite direction to the trial results to change the statistical significance of the findings.The association between eGFR and difference in response between sitagliptin and canagliflozin was linear on a continuous scale indicating that there would be an even greater benefit for canagliflozin at higher eGFR values and greater benefit for sitagliptin at lower eGFR values (Sensitivity analyses show that results did not differ for either of the tested hypotheses when adjusting for study period, when restricted to only those with HbA1c values when on therapy for at least 15 weeks, when adjusting for differences in time intervals between measurements, or when adjusting for those who had >18 weeks of therapy (