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

Stuart J McGurnaghan, Liam Brierley, Thomas M Caparrotta, Paul M McKeigue, Luke A K Blackbourn, Sarah H Wild, Graham P Leese, Rory J McCrimmon, John A McKnight, Ewan R Pearson, John R Petrie, Naveed Sattar, Helen M Colhoun,

REVIEW


31 August 2019

This is an interesting study that confirms previous evidence of SGLT2s on cardiovascular outcomes. I am unsure why only dapagliflozin has only been studied though.


RELEVANCE 2
INNOVATIVENESS 3
APPLICABILITY 2
OVERALL 2

PAPER DETAILS


TITLE

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

ABSTRACT

AIMS/HYPOTHESIS
Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is indicated for improving glycaemic control in type 2 diabetes mellitus. Whether its effects on HbA and other variables, including safety outcomes, in clinical trials are obtained in real-world practice needs to be established.

METHODS
We 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, 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.

RESULTS
Among 8566 people exposed to dapagliflozin over a median of 210 days the crude within-person change in HbA 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 HbA 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/m (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 [1.73 m] (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/INTERPRETATION
Dapagliflozin exposure was associated with reductions in HbA, SBP, body weight and BMI that were at least as large as in clinical trials. Dapagliflozin also prevented the expected rise in HbA and SBP over the period of study.



AUTHOR(S)

Stuart J McGurnaghan, Liam Brierley, Thomas M Caparrotta, Paul M McKeigue, Luke A K Blackbourn, Sarah H Wild, Graham P Leese, Rory J McCrimmon, John A McKnight, Ewan R Pearson, John R Petrie, Naveed Sattar, Helen M Colhoun, ,

JOURNAL

Diabetologia

PLACE

Germany