The effect of dapagliflozin on glycaemic control and other cardiovascular disease risk factors in type 2 diabetes mellitus: a real-world observational study

Aims/hypothesisDapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is indicated for improving glycaemic control in type 2 diabetes mellitus. Whether its effects on HbA(1c) and other variables, including safety outcomes, in clinical trials are obtained in real-world practice needs to be established.MethodsWe used data from the comprehensive national diabetes register, the Scottish Care Information-Diabetes (SCI-Diabetes) collaboration database, available from 2004 to mid-2016. Data within this database were linked to mortality data from the General Registrar, available from the Information Services Division (ISD) of the National Health Service in Scotland. We calculated crude within-person differences between pre- and post-drug-initiation values of HbA(1c), BMI, body weight, systolic blood pressure (SBP) and eGFR. We used mixed-effects regression models to adjust for within-person time trajectories in these measures. For completeness, we evaluated safety outcomes, cardiovascular disease events, lower-limb amputation and diabetic ketoacidosis, focusing on cumulative exposure effects, using Cox proportional hazard models, though power to detect such effects was limited.ResultsAmong 8566 people exposed to dapagliflozin over a median of 210days the crude within-person change in HbA(1c) was -10.41mmol/mol (-0.95%) after 3months' exposure. The crude change after 12months was -12.99mmol/mol (-1.19%) but considering the expected rise over time in HbA(1c) gave a dapagliflozin-exposure-effect estimate of -15.14mmol/mol (95% CI -15.87, -14.41) (-1.39% [95% CI -1.45, -1.32]) at 12months that was maintained thereafter. A drop in SBP of -4.32mmHg (95% CI -4.84, -3.79) on exposure within the first 3months was also maintained thereafter. Reductions in BMI and body weight stabilised by 6months at -0.82kg/m(2) (95% CI -0.87, -0.77) and -2.20kg (95% CI -2.34, -2.06) and were maintained thereafter. eGFR declined initially by -1.81mlmin(-1) [1.73m](-2) (95% CI -2.10, -1.52) at 3months but varied thereafter. There were no significant effects of cumulative drug exposure on safety outcomes.Conclusions/interpretationDapagliflozin exposure was associated with reductions in HbA(1c), SBP, body weight and BMI that were at least as large as in clinical trials. Dapagliflozin also prevented the expected rise in HbA(1c) and SBP over the period of study.