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

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on behalf of the 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 P. +6 more·2019·Diabetologia
DOI 10.1007/s00125-018-4806-9
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Abstract

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. 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. 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. 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.

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  • Use of SGLT2 inhibitors and GLP-1 receptor agonists is paradoxically lower among patients with evidence of or increased risk factors for cardiovascular disease.

    “Despite these recommendations, data from studies in the clinical setting show that use of these newer drug classes have been paradoxically lower among patients with evidence of, or increased risk factors for, CVD.3,4,5,6”

    From Evaluation of Out-of-Pocket Costs and Treatment Intensification With an SGLT2 Inhibitor or GLP-1 RA in Patients With Type 2 Diabetes and Cardiovascular Disease (2023) · cites this paper as [3]

    Table 1 (baseline characteristics, indexed under Discussion; page unavailable) shows that dapagliflozin users had less prior heart failure and stroke than never-users, supporting the claim for some evidence of CVD among users of one SGLT2 inhibitor. But users had higher BMI and systolic blood pressure, and this paper does not establish lower use of SGLT2 inhibitors as a class or of GLP-1 receptor agonists among patients with increased CVD risk factors. (LLM, conf=0.85)

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Authors
on behalf of the Scottish Diabetes Research Network Epidemiology Group, McGurnaghan, S. J., Brierley, L., Caparrotta, T. M., McKeigue, P. M., Blackbourn, L. A. K., Wild, S. H., Leese, G. P., McCrimmon, R. J., McKnight, J. A., Pearson, E. R., Petrie, J. R., Sattar, N., & Colhoun, H. M.
Affiliations
  • Western General Hospital (GB)
  • University of Edinburgh (GB)
  • Ninewells Hospital (GB)
  • University of Glasgow (GB)
Corresponding author
Colhoun, Helen M.
ORCID
Venue
Diabetologia
Publisher
Springer Science and Business Media LLC
Published
2019-01-10
Volume
62
Issue
4
Pages
621-632
ISSN
  • 0012-186X (ISSN-L)
  • 1432-0428
DOI
10.1007/s00125-018-4806-9
OpenAlex
W2910145779
Cited by
46
References
2
Citations by year
2026: 2 · 2025: 1 · 2024: 6 · 2023: 6 · 2022: 11 · 2021: 9 · 2020: 6 · 2019: 5
FWCI
6.31
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetologia (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Discovery Research Portal (University of Dundee) (acceptedVersion, cc-by)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
Funders
AstraZeneca (7462RH)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
Keywords
dapagliflozin, SGLT2 inhibitors, type 2 diabetes, glycemic control, HbA1c, systolic blood pressure, body mass index, EGFR, cardiovascular risk factors, drug safety, lower limb amputation, diabetic ketoacidosis, real-world effectiveness, mortality, within-person change
MeSH terms
Sodium-Glucose Transporter 2 Inhibitors, Aged, Benzhydryl Compounds, Blood Glucose, Blood Pressure, Body Weight, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Female, Glomerular Filtration Rate, Glucosides, Humans, Male, Middle Aged, Risk Factors, Scotland, Systole, Proportional Hazards Models, Databases, Factual, Treatment Outcome, Diabetes Complications, Patient Safety

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