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Comparative cardiovascular safety of glucagon-like peptide-1 receptor agonists versus other antidiabetic drugs in routine care: a cohort study.
Diabetes Obes Metab. 2016 08; 18(8):755-65.DO

Abstract

AIMS

To evaluate the comparative cardiovascular disease (CVD) safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in head-to-head comparisons with dipeptidyl peptidase-4 (DPP-4) inhibitors, sulphonylureas or insulin, when added to metformin, as used in 'real-world' patients with type 2 diabetes mellitus (T2DM).

METHODS

Within a large US commercial health plan database linked to laboratory test results, we identified three pairwise 1 : 1 propensity-score-matched cohorts of patients with T2DM aged ≥18 years treated with metformin who initiated a GLP-1 RA or a comparator, i.e. DPP-4 inhibitor (n = 35 534), second-generation sulphonylureas (n = 28 138) or insulin (n = 47 068), between 2005 and 2013. We examined the association between drug initiation and a composite CVD endpoint, comprising hospitalizations for acute myocardial infarction, unstable angina, stroke or coronary revascularization.

RESULTS

During the course of 1 year, there were 13.9 and 13.7 CVD events per 1000 person-years among propensity-score-matched initiators of GLP-1 RAs versus DPP-4 inhibitors [hazard ratio (HR) 1.02; 95% confidence interval (CI) 0.84-1.24]; and 12.1 versus 14.0 events among initiators of GLP-1 RAs versus sulphonylureas (HR 0.86; 95% CI 0.69-1.08). The effect estimates for GLP-1 RAs versus insulin were sensitive to the adjustment for glycated haemoglobin, after which the HR was 1.01 (95% CI 0.73-1.41). Results were robust across several sensitivity analyses, including an as-treated analysis considering up to 8.7 years of follow-up.

CONCLUSIONS

This large study, performing head-to-head comparisons of GLP-1 RAs with other antidiabetic agents in real-world patients, provides estimates of relative safety precise enough to exclude large differences in CVD risk and adds further understanding to results from recent clinical trials.

Authors+Show Affiliations

Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.Divisions of Cardiovascular and Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.Clinical Research, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Division of Rheumatology, Allergy and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Pub Type(s)

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

Language

eng

PubMed ID

27003762

Citation

Patorno, E, et al. "Comparative Cardiovascular Safety of Glucagon-like Peptide-1 Receptor Agonists Versus Other Antidiabetic Drugs in Routine Care: a Cohort Study." Diabetes, Obesity & Metabolism, vol. 18, no. 8, 2016, pp. 755-65.
Patorno E, Everett BM, Goldfine AB, et al. Comparative cardiovascular safety of glucagon-like peptide-1 receptor agonists versus other antidiabetic drugs in routine care: a cohort study. Diabetes Obes Metab. 2016;18(8):755-65.
Patorno, E., Everett, B. M., Goldfine, A. B., Glynn, R. J., Liu, J., Gopalakrishnan, C., & Kim, S. C. (2016). Comparative cardiovascular safety of glucagon-like peptide-1 receptor agonists versus other antidiabetic drugs in routine care: a cohort study. Diabetes, Obesity & Metabolism, 18(8), 755-65. https://doi.org/10.1111/dom.12665
Patorno E, et al. Comparative Cardiovascular Safety of Glucagon-like Peptide-1 Receptor Agonists Versus Other Antidiabetic Drugs in Routine Care: a Cohort Study. Diabetes Obes Metab. 2016;18(8):755-65. PubMed PMID: 27003762.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative cardiovascular safety of glucagon-like peptide-1 receptor agonists versus other antidiabetic drugs in routine care: a cohort study. AU - Patorno,E, AU - Everett,B M, AU - Goldfine,A B, AU - Glynn,R J, AU - Liu,J, AU - Gopalakrishnan,C, AU - Kim,S C, Y1 - 2016/05/02/ PY - 2015/12/29/received PY - 2016/01/23/revised PY - 2016/03/17/accepted PY - 2016/3/23/entrez PY - 2016/3/24/pubmed PY - 2017/11/8/medline KW - DPP-4 inhibitor KW - GLP-1 analogue KW - cardiovascular disease KW - insulin therapy KW - pharmaco-epidemiology KW - sulphonylureas SP - 755 EP - 65 JF - Diabetes, obesity & metabolism JO - Diabetes Obes Metab VL - 18 IS - 8 N2 - AIMS: To evaluate the comparative cardiovascular disease (CVD) safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in head-to-head comparisons with dipeptidyl peptidase-4 (DPP-4) inhibitors, sulphonylureas or insulin, when added to metformin, as used in 'real-world' patients with type 2 diabetes mellitus (T2DM). METHODS: Within a large US commercial health plan database linked to laboratory test results, we identified three pairwise 1 : 1 propensity-score-matched cohorts of patients with T2DM aged ≥18 years treated with metformin who initiated a GLP-1 RA or a comparator, i.e. DPP-4 inhibitor (n = 35 534), second-generation sulphonylureas (n = 28 138) or insulin (n = 47 068), between 2005 and 2013. We examined the association between drug initiation and a composite CVD endpoint, comprising hospitalizations for acute myocardial infarction, unstable angina, stroke or coronary revascularization. RESULTS: During the course of 1 year, there were 13.9 and 13.7 CVD events per 1000 person-years among propensity-score-matched initiators of GLP-1 RAs versus DPP-4 inhibitors [hazard ratio (HR) 1.02; 95% confidence interval (CI) 0.84-1.24]; and 12.1 versus 14.0 events among initiators of GLP-1 RAs versus sulphonylureas (HR 0.86; 95% CI 0.69-1.08). The effect estimates for GLP-1 RAs versus insulin were sensitive to the adjustment for glycated haemoglobin, after which the HR was 1.01 (95% CI 0.73-1.41). Results were robust across several sensitivity analyses, including an as-treated analysis considering up to 8.7 years of follow-up. CONCLUSIONS: This large study, performing head-to-head comparisons of GLP-1 RAs with other antidiabetic agents in real-world patients, provides estimates of relative safety precise enough to exclude large differences in CVD risk and adds further understanding to results from recent clinical trials. SN - 1463-1326 UR - https://www.unboundmedicine.com/medline/citation/27003762/Comparative_cardiovascular_safety_of_glucagon_like_peptide_1_receptor_agonists_versus_other_antidiabetic_drugs_in_routine_care:_a_cohort_study_ L2 - https://doi.org/10.1111/dom.12665 DB - PRIME DP - Unbound Medicine ER -