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Comparative risk of major cardiovascular events associated with second-line antidiabetic treatments: a retrospective cohort study using UK primary care data linked to hospitalization and mortality records.
Diabetes Obes Metab. 2016 09; 18(9):916-24.DO

Abstract

AIMS

To examine the risk of major cardiovascular events associated with second-line diabetes therapies, in patients with type 2 diabetes, after adjusting for known cardiovascular risk factors.

METHODS

This was a retrospective cohort study of patients prescribed second-line regimens between 1998 and 2011 after first-line metformin. The UK Clinical Practice Research Datalink, with linked national hospitalization and mortality data, for the period up to December 2013, was used. Inverse probability of treatment-weighted time-varying Cox regression models was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for developing a major cardiovascular event (cardiovascular death, myocardial infarction, stroke, acute coronary syndrome, unstable angina, or coronary revascularization) associated with second-line therapies. Analyses adjusted for patient demographic characteristics, comorbidities, glycated haemoglobin, socio-economic status, ethnicity, smoking status and concurrent medications.

RESULTS

A total of 10 118 initiators of a second-line add-on to metformin of either a sulphonylurea (n = 6740), dipeptidyl peptidase-4 (DPP-4) inhibitor (n = 1030) or thiazolidinedione (n = 2348) were identified. After a mean (standard deviation) of 2.4 (1.9) years of follow-up, 386, 36 and 95 major cardiovascular events occurred in sulphonylurea-, DPP-4 inhibitor- and thiazolidinedione-initiators, respectively. In comparison with the metformin-sulphonylurea regimen, adjusted HRs were 0.78 (95% CI 0.55; 1.11) for the metformin-DPP-4 inhibitor regimen and 0.68 (95% CI 0.54; 0.85) for the metformin-thiazolidinedione regimen.

CONCLUSIONS

Thiazolidinedione add-on treatments to metformin were associated with lower risks of major cardiovascular disease or cardiovascular death compared with sulphonylurea add-on treatment to metformin. Lower, but non-statistically significant, risks were also found with DPP-4 inhibitor add-on therapies.

Authors+Show Affiliations

Centre for Pharmacoepidemiology and Drug Safety, Manchester Pharmacy School, University of Manchester, Manchester, UK. Department of Pharmaceutics, Faculty of Pharmacy, University of Tripoli, Tripoli, Libya.Centre for Pharmacoepidemiology and Drug Safety, Manchester Pharmacy School, University of Manchester, Manchester, UK.Endocrinology and Diabetes Research Group, Institute of Human Development, University of Manchester, Manchester, UK. Manchester Diabetes Centre, Manchester Academic Health Science Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.Centre for Biostatistics, Institute of Population Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.Centre for Pharmacoepidemiology and Drug Safety, Manchester Pharmacy School, University of Manchester, Manchester, UK.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27177784

Citation

Zghebi, S S., et al. "Comparative Risk of Major Cardiovascular Events Associated With Second-line Antidiabetic Treatments: a Retrospective Cohort Study Using UK Primary Care Data Linked to Hospitalization and Mortality Records." Diabetes, Obesity & Metabolism, vol. 18, no. 9, 2016, pp. 916-24.
Zghebi SS, Steinke DT, Rutter MK, et al. Comparative risk of major cardiovascular events associated with second-line antidiabetic treatments: a retrospective cohort study using UK primary care data linked to hospitalization and mortality records. Diabetes Obes Metab. 2016;18(9):916-24.
Zghebi, S. S., Steinke, D. T., Rutter, M. K., Emsley, R. A., & Ashcroft, D. M. (2016). Comparative risk of major cardiovascular events associated with second-line antidiabetic treatments: a retrospective cohort study using UK primary care data linked to hospitalization and mortality records. Diabetes, Obesity & Metabolism, 18(9), 916-24. https://doi.org/10.1111/dom.12692
Zghebi SS, et al. Comparative Risk of Major Cardiovascular Events Associated With Second-line Antidiabetic Treatments: a Retrospective Cohort Study Using UK Primary Care Data Linked to Hospitalization and Mortality Records. Diabetes Obes Metab. 2016;18(9):916-24. PubMed PMID: 27177784.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative risk of major cardiovascular events associated with second-line antidiabetic treatments: a retrospective cohort study using UK primary care data linked to hospitalization and mortality records. AU - Zghebi,S S, AU - Steinke,D T, AU - Rutter,M K, AU - Emsley,R A, AU - Ashcroft,D M, Y1 - 2016/06/30/ PY - 2016/02/11/received PY - 2016/05/09/revised PY - 2016/05/11/accepted PY - 2016/5/15/entrez PY - 2016/5/15/pubmed PY - 2017/11/1/medline KW - DPP-4 inhibitor KW - cardiovascular disease KW - pharmaco-epidemiology KW - sulphonylureas KW - thiazolidinediones KW - type 2 diabetes SP - 916 EP - 24 JF - Diabetes, obesity & metabolism JO - Diabetes Obes Metab VL - 18 IS - 9 N2 - AIMS: To examine the risk of major cardiovascular events associated with second-line diabetes therapies, in patients with type 2 diabetes, after adjusting for known cardiovascular risk factors. METHODS: This was a retrospective cohort study of patients prescribed second-line regimens between 1998 and 2011 after first-line metformin. The UK Clinical Practice Research Datalink, with linked national hospitalization and mortality data, for the period up to December 2013, was used. Inverse probability of treatment-weighted time-varying Cox regression models was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for developing a major cardiovascular event (cardiovascular death, myocardial infarction, stroke, acute coronary syndrome, unstable angina, or coronary revascularization) associated with second-line therapies. Analyses adjusted for patient demographic characteristics, comorbidities, glycated haemoglobin, socio-economic status, ethnicity, smoking status and concurrent medications. RESULTS: A total of 10 118 initiators of a second-line add-on to metformin of either a sulphonylurea (n = 6740), dipeptidyl peptidase-4 (DPP-4) inhibitor (n = 1030) or thiazolidinedione (n = 2348) were identified. After a mean (standard deviation) of 2.4 (1.9) years of follow-up, 386, 36 and 95 major cardiovascular events occurred in sulphonylurea-, DPP-4 inhibitor- and thiazolidinedione-initiators, respectively. In comparison with the metformin-sulphonylurea regimen, adjusted HRs were 0.78 (95% CI 0.55; 1.11) for the metformin-DPP-4 inhibitor regimen and 0.68 (95% CI 0.54; 0.85) for the metformin-thiazolidinedione regimen. CONCLUSIONS: Thiazolidinedione add-on treatments to metformin were associated with lower risks of major cardiovascular disease or cardiovascular death compared with sulphonylurea add-on treatment to metformin. Lower, but non-statistically significant, risks were also found with DPP-4 inhibitor add-on therapies. SN - 1463-1326 UR - https://www.unboundmedicine.com/medline/citation/27177784/Comparative_risk_of_major_cardiovascular_events_associated_with_second_line_antidiabetic_treatments:_a_retrospective_cohort_study_using_UK_primary_care_data_linked_to_hospitalization_and_mortality_records_ L2 - https://doi.org/10.1111/dom.12692 DB - PRIME DP - Unbound Medicine ER -