Abstract
Aims/hypothesisDapagliflozin, a sodium–glucose cotransporter 2 (SGLT2) inhibitor, is indicated for improving glycaemic control in type 2 diabetes mellitus. Whether its effects on HbA1c 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 HbA1c, 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 210 days the crude within-person change in HbA1c was −10.41 mmol/mol (−0.95%) after 3 months’ exposure. The crude change after 12 months was −12.99 mmol/mol (−1.19%) but considering the expected rise over time in HbA1c gave a dapagliflozin-exposure-effect estimate of −15.14 mmol/mol (95% CI −15.87, −14.41) (−1.39% [95% CI −1.45, −1.32]) at 12 months that was maintained thereafter. A drop in SBP of −4.32 mmHg (95% CI −4.84, −3.79) on exposure within the first 3 months was also maintained thereafter. Reductions in BMI and body weight stabilised by 6 months at −0.82 kg/m2 (95% CI −0.87, −0.77) and −2.20 kg (95% CI −2.34, −2.06) and were maintained thereafter. eGFR declined initially by −1.81 ml min−1 [1.73 m]−2 (95% CI −2.10, −1.52) at 3 months but varied thereafter. There were no significant effects of cumulative drug exposure on safety outcomes.Conclusions/interpretationDapagliflozin exposure was associated with reductions in HbA1c, SBP, body weight and BMI that were at least as large as in clinical trials. Dapagliflozin also prevented the expected rise in HbA1c and SBP over the period of study.
Highlights
Sodium–glucose cotransporter 2 (SGLT2) inhibitors block the SGLT2 within the proximal renal tubule, reducing glucose and sodium reabsorption and increasing glycosuria and fluid loss
For analyses with outcomes of systolic blood pressure (SBP) and for cardiovascular disease (CVD) events, person-time was right-censored upon initiating a new drug for CVD that was not received at dapagliflozin initiation or ceasing a CVD drug that was coprescribed at dapagliflozin initiation
We describe usage trends of dapagliflozin in individuals with type 2 diabetes in Scotland
Summary
Sodium–glucose cotransporter 2 (SGLT2) inhibitors block the SGLT2 within the proximal renal tubule, reducing glucose and sodium reabsorption and increasing glycosuria and fluid loss. Dapagliflozin is a new SGLT2 inhibitor indicated alongside diet and exercise for improving glycaemic control in adults with type 2 diabetes (licensed in Europe in 2012 [1] and the USA in 2014 [2]). In large-scale placebo-controlled cardiovascular disease (CVD) outcome trials, other SGLT2 inhibitors (empagliflozin [14] and canagliflozin [15]) were shown to reduce major CVD events. The results for the dapagliflozin DECLARE CVD outcome trial have not yet been published it has been reported that the primary safety endpoint of non-inferiority for major adverse cardiovascular events was met and that there was a significant reduction in one of two primary efficacy CVD endpoints [16, 17]
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