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The effects of dual-therapy intensification with insulin or dipeptidylpeptidase-4 inhibitor on cardiovascular events and all-cause mortality in patients with type 2 diabetes: A retrospective cohort study.
Diab Vasc Dis Res. 2017 07; 14(4):295-303.DV

Abstract

PURPOSE

To compare time to a composite endpoint of non-fatal acute myocardial infarction, non-fatal stroke or all-cause mortality in patients with type 2 diabetes mellitus who had their treatment intensified with a dipeptidylpeptidase-4 inhibitor or insulin following dual-therapy (metformin plus sulfonylurea) failure.

METHODS

A retrospective cohort study was conducted on 5238 patients newly treated with either a dipeptidylpeptidase-4 inhibitor or insulin following dual-therapy failure (2007-2014). Data were sourced from UK General Practices. The risk of the composite outcome was compared between two treatment groups: metformin + sulfonylurea + insulin (n = 1584) and metformin + sulfonylurea + dipeptidylpeptidase-4 inhibitor (n = 3654), while adjusting for baseline covariates. Follow-up was for up to 5 years. Propensity score matching analysis and Cox proportional hazard models were employed.

RESULTS

Overall, 123 and 171 composite outcome events occurred among patients who added insulin versus dipeptidylpeptidase-4 inhibitor, respectively (44.5 vs 14.6 events per 1000 person-years). Addition of insulin was associated with a significantly higher hazard ratio versus the addition of a dipeptidylpeptidase-4 inhibitor (adjusted hazard ratio = 2.6, 95% confidence interval: 1.9-3.4; p < 0.01), an effect that was more pronounced in obese (body mass index: 30-34.9 kg/m2) patients (corresponding adjusted hazard ratio 3.6, 95% confidence interval: 2.3-5.6; p < 0.01).

CONCLUSION

In routine clinical practice, intensification of metformin + sulfonylurea therapy by adding insulin is associated with increased risk of cardiovascular events and death compared with adding a dipeptidylpeptidase-4 inhibitor. These findings are in line with suggestions from previous studies regarding the cardiovascular safety of insulin in type 2 diabetes mellitus, but should be interpreted with caution.

Authors+Show Affiliations

1 Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, UK.2 Research Design Services East Midlands, School of Medicine, University of Nottingham, Nottingham, UK.1 Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, UK.1 Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, UK.

Pub Type(s)

Comparative Study
Journal Article
Observational Study

Language

eng

PubMed ID

28330386

Citation

Jil, Mamza, et al. "The Effects of Dual-therapy Intensification With Insulin or Dipeptidylpeptidase-4 Inhibitor On Cardiovascular Events and All-cause Mortality in Patients With Type 2 Diabetes: a Retrospective Cohort Study." Diabetes & Vascular Disease Research, vol. 14, no. 4, 2017, pp. 295-303.
Jil M, Rajnikant M, Richard D, et al. The effects of dual-therapy intensification with insulin or dipeptidylpeptidase-4 inhibitor on cardiovascular events and all-cause mortality in patients with type 2 diabetes: A retrospective cohort study. Diab Vasc Dis Res. 2017;14(4):295-303.
Jil, M., Rajnikant, M., Richard, D., & Iskandar, I. (2017). The effects of dual-therapy intensification with insulin or dipeptidylpeptidase-4 inhibitor on cardiovascular events and all-cause mortality in patients with type 2 diabetes: A retrospective cohort study. Diabetes & Vascular Disease Research, 14(4), 295-303. https://doi.org/10.1177/1479164116687102
Jil M, et al. The Effects of Dual-therapy Intensification With Insulin or Dipeptidylpeptidase-4 Inhibitor On Cardiovascular Events and All-cause Mortality in Patients With Type 2 Diabetes: a Retrospective Cohort Study. Diab Vasc Dis Res. 2017;14(4):295-303. PubMed PMID: 28330386.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effects of dual-therapy intensification with insulin or dipeptidylpeptidase-4 inhibitor on cardiovascular events and all-cause mortality in patients with type 2 diabetes: A retrospective cohort study. AU - Jil,Mamza, AU - Rajnikant,Mehta, AU - Richard,Donnelly, AU - Iskandar,Idris, Y1 - 2017/03/23/ PY - 2017/3/24/pubmed PY - 2017/12/13/medline PY - 2017/3/24/entrez KW - Insulin KW - cardiovascular KW - gliptins KW - intensification SP - 295 EP - 303 JF - Diabetes & vascular disease research JO - Diab Vasc Dis Res VL - 14 IS - 4 N2 - PURPOSE: To compare time to a composite endpoint of non-fatal acute myocardial infarction, non-fatal stroke or all-cause mortality in patients with type 2 diabetes mellitus who had their treatment intensified with a dipeptidylpeptidase-4 inhibitor or insulin following dual-therapy (metformin plus sulfonylurea) failure. METHODS: A retrospective cohort study was conducted on 5238 patients newly treated with either a dipeptidylpeptidase-4 inhibitor or insulin following dual-therapy failure (2007-2014). Data were sourced from UK General Practices. The risk of the composite outcome was compared between two treatment groups: metformin + sulfonylurea + insulin (n = 1584) and metformin + sulfonylurea + dipeptidylpeptidase-4 inhibitor (n = 3654), while adjusting for baseline covariates. Follow-up was for up to 5 years. Propensity score matching analysis and Cox proportional hazard models were employed. RESULTS: Overall, 123 and 171 composite outcome events occurred among patients who added insulin versus dipeptidylpeptidase-4 inhibitor, respectively (44.5 vs 14.6 events per 1000 person-years). Addition of insulin was associated with a significantly higher hazard ratio versus the addition of a dipeptidylpeptidase-4 inhibitor (adjusted hazard ratio = 2.6, 95% confidence interval: 1.9-3.4; p < 0.01), an effect that was more pronounced in obese (body mass index: 30-34.9 kg/m2) patients (corresponding adjusted hazard ratio 3.6, 95% confidence interval: 2.3-5.6; p < 0.01). CONCLUSION: In routine clinical practice, intensification of metformin + sulfonylurea therapy by adding insulin is associated with increased risk of cardiovascular events and death compared with adding a dipeptidylpeptidase-4 inhibitor. These findings are in line with suggestions from previous studies regarding the cardiovascular safety of insulin in type 2 diabetes mellitus, but should be interpreted with caution. SN - 1752-8984 UR - https://www.unboundmedicine.com/medline/citation/28330386/The_effects_of_dual_therapy_intensification_with_insulin_or_dipeptidylpeptidase_4_inhibitor_on_cardiovascular_events_and_all_cause_mortality_in_patients_with_type_2_diabetes:_A_retrospective_cohort_study_ L2 - https://journals.sagepub.com/doi/10.1177/1479164116687102?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -