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

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

Research output: Contribution to journalArticle

4 Citations (Scopus)
60 Downloads (Pure)

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 1c 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 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. Results: Among 8566 people exposed to dapagliflozin over a median of 210 days the crude within-person change in HbA 1c 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 1c 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 2 (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/interpretation: Dapagliflozin 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.

Original languageEnglish
Pages (from-to)621-632
Number of pages12
JournalDiabetologia
Volume62
Issue number4
Early online date10 Jan 2019
DOIs
Publication statusPublished - Apr 2019

Fingerprint

Type 2 Diabetes Mellitus
Observational Studies
Cardiovascular Diseases
Blood Pressure
Body Weight
Safety
Clinical Trials
Pharmaceutical Preparations
Databases
Diabetic Ketoacidosis
Information Services
2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
National Health Programs
Scotland
Amputation
Proportional Hazards Models
Lower Extremity
Mortality

Keywords

  • Dapagliflozin
  • Glycaemic control
  • Type 2 diabetes

Cite this

Scottish Diabetes Research Network Epidemiology Group, McGurnaghan, S. J., Brierley, L., Caparrotta, T. M. ., McKeigue, P. M., Blackbourn, L. A. K., ... Colhoun, H. M. (2019). The effect of dapagliflozin on glycaemic control and other cardiovascular disease risk factors in type 2 diabetes mellitus: a real-world observational study. Diabetologia, 62(4), 621-632. https://doi.org/10.1007/s00125-018-4806-9
Scottish Diabetes Research Network Epidemiology Group ; McGurnaghan, Stuart J. ; Brierley, Liam ; Caparrotta, Thomas M . ; McKeigue, Paul M. ; Blackbourn, Luke A. K. ; Wild, Sarah H. ; Leese, Graham ; McCrimmon, Rory ; McKnight, John A. ; Pearson, Ewan ; Petrie, John R. ; Sattar, Naveed ; Colhoun, Helen M. / The effect of dapagliflozin on glycaemic control and other cardiovascular disease risk factors in type 2 diabetes mellitus : a real-world observational study. In: Diabetologia. 2019 ; Vol. 62, No. 4. pp. 621-632.
@article{58b3ee58f73a40bd9da9dc31eb10bd08,
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 1c 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 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. Results: Among 8566 people exposed to dapagliflozin over a median of 210 days the crude within-person change in HbA 1c 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 1c 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 2 (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/interpretation: Dapagliflozin 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.",
keywords = "Dapagliflozin, Glycaemic control, Type 2 diabetes",
author = "{Scottish Diabetes Research Network Epidemiology Group} and McGurnaghan, {Stuart J.} and Liam Brierley and Caparrotta, {Thomas M .} and McKeigue, {Paul M.} and Blackbourn, {Luke A. K.} and Wild, {Sarah H.} and Graham Leese and Rory McCrimmon and McKnight, {John A.} and Ewan Pearson and Petrie, {John R.} and Naveed Sattar and Colhoun, {Helen M.}",
note = "This study was funded by Astra Zeneca (grant ref 7462RH). Astra Zeneca had no right of veto over study design, choice of statistical methods, data analysis, data generation, data interpretation or writing of this manuscript, all of which were carried out by the authors. They were allowed to see and comment on the draft, their comments being that a quadrant plot would be useful, that effects in off-licence users should be detailed and that effects on weight should be presented. The corresponding author, HMC, had full access to the data in the study, drew up the analysis plan, supervised LBr and SM doing the analyses and had final responsibility for the decision to submit for publication.",
year = "2019",
month = "4",
doi = "10.1007/s00125-018-4806-9",
language = "English",
volume = "62",
pages = "621--632",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "4",

}

Scottish Diabetes Research Network Epidemiology Group, McGurnaghan, SJ, Brierley, L, Caparrotta, TM, McKeigue, PM, Blackbourn, LAK, Wild, SH, Leese, G, McCrimmon, R, McKnight, JA, Pearson, E, Petrie, JR, Sattar, N & Colhoun, HM 2019, 'The effect of dapagliflozin on glycaemic control and other cardiovascular disease risk factors in type 2 diabetes mellitus: a real-world observational study', Diabetologia, vol. 62, no. 4, pp. 621-632. https://doi.org/10.1007/s00125-018-4806-9

The effect of dapagliflozin on glycaemic control and other cardiovascular disease risk factors in type 2 diabetes mellitus : a real-world observational study. / Scottish Diabetes Research Network Epidemiology Group; McGurnaghan, Stuart J.; Brierley, Liam ; Caparrotta, Thomas M .; McKeigue, Paul M.; Blackbourn, Luke A. K.; Wild, Sarah H.; Leese, Graham; McCrimmon, Rory; McKnight, John A. ; Pearson, Ewan; Petrie, John R.; Sattar, Naveed; Colhoun, Helen M.

In: Diabetologia, Vol. 62, No. 4, 04.2019, p. 621-632.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The effect of dapagliflozin on glycaemic control and other cardiovascular disease risk factors in type 2 diabetes mellitus

T2 - a real-world observational study

AU - Scottish Diabetes Research Network Epidemiology Group

AU - McGurnaghan, Stuart J.

AU - Brierley, Liam

AU - Caparrotta, Thomas M .

AU - McKeigue, Paul M.

AU - Blackbourn, Luke A. K.

AU - Wild, Sarah H.

AU - Leese, Graham

AU - McCrimmon, Rory

AU - McKnight, John A.

AU - Pearson, Ewan

AU - Petrie, John R.

AU - Sattar, Naveed

AU - Colhoun, Helen M.

N1 - This study was funded by Astra Zeneca (grant ref 7462RH). Astra Zeneca had no right of veto over study design, choice of statistical methods, data analysis, data generation, data interpretation or writing of this manuscript, all of which were carried out by the authors. They were allowed to see and comment on the draft, their comments being that a quadrant plot would be useful, that effects in off-licence users should be detailed and that effects on weight should be presented. The corresponding author, HMC, had full access to the data in the study, drew up the analysis plan, supervised LBr and SM doing the analyses and had final responsibility for the decision to submit for publication.

PY - 2019/4

Y1 - 2019/4

N2 - 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 1c 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 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. Results: Among 8566 people exposed to dapagliflozin over a median of 210 days the crude within-person change in HbA 1c 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 1c 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 2 (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/interpretation: Dapagliflozin 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.

AB - 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 1c 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 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. Results: Among 8566 people exposed to dapagliflozin over a median of 210 days the crude within-person change in HbA 1c 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 1c 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 2 (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/interpretation: Dapagliflozin 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.

KW - Dapagliflozin

KW - Glycaemic control

KW - Type 2 diabetes

UR - http://www.scopus.com/inward/record.url?scp=85059849771&partnerID=8YFLogxK

U2 - 10.1007/s00125-018-4806-9

DO - 10.1007/s00125-018-4806-9

M3 - Article

C2 - 30631892

VL - 62

SP - 621

EP - 632

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 4

ER -

Scottish Diabetes Research Network Epidemiology Group, McGurnaghan SJ, Brierley L, Caparrotta TM, McKeigue PM, Blackbourn LAK et al. The effect of dapagliflozin on glycaemic control and other cardiovascular disease risk factors in type 2 diabetes mellitus: a real-world observational study. Diabetologia. 2019 Apr;62(4):621-632. https://doi.org/10.1007/s00125-018-4806-9