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Impact of metformin use on the cardiovascular effects of dipeptidyl peptidase-4 inhibitors: An analysis of Medicare claims data from 2007 to 2015.
Diabetes Obes Metab. 2019 04; 21(4):854-865.DO

Abstract

AIMS

To examine the outcomes of dipeptidyl peptidase-4 (DPP-4) inhibitor initiation with and without concurrent metformin treatment.

MATERIALS AND METHODS

We identified Medicare enrollees initiating a DPP-4 inhibitor, a sulphonylurea or a thiazolidinedione. Using propensity-score-weighted Poisson models, we evaluated 1-year cardiovascular (CV) outcome incidence among initiators of DPP-4 inhibitors versus comparators in subgroups with and without concurrent metformin use, and assessed the interaction between initiation drug and metformin. Outcomes included mortality, non-fatal myocardial infarction (MI), stroke, and a composite outcome.

RESULTS

For the DPP-4 inhibitor (n = 13 391) versus sulphonylurea (n = 33 206) comparison, rate differences in composite outcome incidence favoured DPP-4 inhibitors: -2.0/100 person-years among metformin users (95% confidence interval [CI] -2.7 to -1.3) and - 1.0/100 person-years (95% CI -1.8 to -0.2) among metformin non-users. Similar rate difference trends among metformin users and non-users were seen for mortality (-1.5/100 person-years [95% CI -2.1 to -0.9] and -0.7/100 person-years [95% CI -1.4 to 0.0]) and non-fatal MI (-0.5/100 person-years [95% CI -0.8, -0.3] and 0.1/100 person-years [95% CI -0.2 to 0.4]). The interaction between DPP-4 inhibitor initiation and metformin was statistically significant for non-fatal MI (P = 0.008). For the DPP-4 inhibitor (n = 22 210) versus thiazolidinedione (n = 9517) comparison, rate differences in composite outcome incidence for DPP-4 inhibitor initiation were -0.6/100 person-years (95% CI -1.5 to 0.2) among metformin users and 1.0 (95% CI 0.0 to 2.0) among metformin non-users. Similar rate difference trends among metformin users and non-users were seen for mortality (-0.5/100 person-years [95% CI -1.3 to 0.1] and 0.8/100 person-years [95% CI -0.0 to 1.7]) and non-fatal MI (-0.1/100 person-years [95% CI -0.4 to 0.2] and 0.2/100 person-years [95% CI -0.1 to 0.6]). The interaction between DPP-4 inhibitor initiation and metformin was statistically significant for the composite outcome (P = 0.024) and mortality (P = 0.023).

CONCLUSION

Incidence rate differences in multiple CV outcomes appeared more favourable when DPP-4 inhibitor initiation occurred in the presence of metformin, suggesting a possible interaction between DPP-4 inhibitors and metformin.

Authors+Show Affiliations

Center for Health Services Research in Primary Care, Durham VAMC, Durham, North Carolina. Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Duke University, Durham, North Carolina.Real World Evidence and Epidemiology, GlaxoSmithKline, Collegeville, Pennsylvania. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina.Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina.Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina.Department of Medicine, Division of Endocrinology and Metabolism, University of North Carolina, Chapel Hill, North Carolina.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

30456843

Citation

Crowley, Matthew J., et al. "Impact of Metformin Use On the Cardiovascular Effects of Dipeptidyl Peptidase-4 Inhibitors: an Analysis of Medicare Claims Data From 2007 to 2015." Diabetes, Obesity & Metabolism, vol. 21, no. 4, 2019, pp. 854-865.
Crowley MJ, Gokhale M, Pate V, et al. Impact of metformin use on the cardiovascular effects of dipeptidyl peptidase-4 inhibitors: An analysis of Medicare claims data from 2007 to 2015. Diabetes Obes Metab. 2019;21(4):854-865.
Crowley, M. J., Gokhale, M., Pate, V., Stürmer, T., & Buse, J. B. (2019). Impact of metformin use on the cardiovascular effects of dipeptidyl peptidase-4 inhibitors: An analysis of Medicare claims data from 2007 to 2015. Diabetes, Obesity & Metabolism, 21(4), 854-865. https://doi.org/10.1111/dom.13589
Crowley MJ, et al. Impact of Metformin Use On the Cardiovascular Effects of Dipeptidyl Peptidase-4 Inhibitors: an Analysis of Medicare Claims Data From 2007 to 2015. Diabetes Obes Metab. 2019;21(4):854-865. PubMed PMID: 30456843.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of metformin use on the cardiovascular effects of dipeptidyl peptidase-4 inhibitors: An analysis of Medicare claims data from 2007 to 2015. AU - Crowley,Matthew J, AU - Gokhale,Mugdha, AU - Pate,Virginia, AU - Stürmer,Til, AU - Buse,John B, Y1 - 2018/12/18/ PY - 2018/10/08/received PY - 2018/11/06/revised PY - 2018/11/15/accepted PY - 2018/11/21/pubmed PY - 2020/9/8/medline PY - 2018/11/21/entrez KW - DPP-4 inhibitor KW - cardiovascular disease KW - metformin KW - pharmaco-epidemiology KW - type 2 diabetes SP - 854 EP - 865 JF - Diabetes, obesity & metabolism JO - Diabetes Obes Metab VL - 21 IS - 4 N2 - AIMS: To examine the outcomes of dipeptidyl peptidase-4 (DPP-4) inhibitor initiation with and without concurrent metformin treatment. MATERIALS AND METHODS: We identified Medicare enrollees initiating a DPP-4 inhibitor, a sulphonylurea or a thiazolidinedione. Using propensity-score-weighted Poisson models, we evaluated 1-year cardiovascular (CV) outcome incidence among initiators of DPP-4 inhibitors versus comparators in subgroups with and without concurrent metformin use, and assessed the interaction between initiation drug and metformin. Outcomes included mortality, non-fatal myocardial infarction (MI), stroke, and a composite outcome. RESULTS: For the DPP-4 inhibitor (n = 13 391) versus sulphonylurea (n = 33 206) comparison, rate differences in composite outcome incidence favoured DPP-4 inhibitors: -2.0/100 person-years among metformin users (95% confidence interval [CI] -2.7 to -1.3) and - 1.0/100 person-years (95% CI -1.8 to -0.2) among metformin non-users. Similar rate difference trends among metformin users and non-users were seen for mortality (-1.5/100 person-years [95% CI -2.1 to -0.9] and -0.7/100 person-years [95% CI -1.4 to 0.0]) and non-fatal MI (-0.5/100 person-years [95% CI -0.8, -0.3] and 0.1/100 person-years [95% CI -0.2 to 0.4]). The interaction between DPP-4 inhibitor initiation and metformin was statistically significant for non-fatal MI (P = 0.008). For the DPP-4 inhibitor (n = 22 210) versus thiazolidinedione (n = 9517) comparison, rate differences in composite outcome incidence for DPP-4 inhibitor initiation were -0.6/100 person-years (95% CI -1.5 to 0.2) among metformin users and 1.0 (95% CI 0.0 to 2.0) among metformin non-users. Similar rate difference trends among metformin users and non-users were seen for mortality (-0.5/100 person-years [95% CI -1.3 to 0.1] and 0.8/100 person-years [95% CI -0.0 to 1.7]) and non-fatal MI (-0.1/100 person-years [95% CI -0.4 to 0.2] and 0.2/100 person-years [95% CI -0.1 to 0.6]). The interaction between DPP-4 inhibitor initiation and metformin was statistically significant for the composite outcome (P = 0.024) and mortality (P = 0.023). CONCLUSION: Incidence rate differences in multiple CV outcomes appeared more favourable when DPP-4 inhibitor initiation occurred in the presence of metformin, suggesting a possible interaction between DPP-4 inhibitors and metformin. SN - 1463-1326 UR - https://www.unboundmedicine.com/medline/citation/30456843/Impact_of_metformin_use_on_the_cardiovascular_effects_of_dipeptidyl_peptidase_4_inhibitors:_An_analysis_of_Medicare_claims_data_from_2007_to_2015_ L2 - https://doi.org/10.1111/dom.13589 DB - PRIME DP - Unbound Medicine ER -