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Cardiovascular outcomes, heart failure and mortality in type 2 diabetic patients treated with glucagon-like peptide 1 receptor agonists (GLP-1 RAs): A systematic review and meta-analysis of observational cohort studies.
Int J Clin Pract. 2020 May 25 [Online ahead of print]IJ

Abstract

BACKGROUND

Cardiovascular outcomes trials (CVOTs) have assessed the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on major adverse cardiovascular events (MACE) and mortality in high cardiovascular (CV) risk populations. Observational research can provide complementary evidence about these effects in unselected populations.

AIM

To systematically review retrospective observational cohort studies conducted in electronic healthcare databases (EHDs) assessing GLP-1 RAs´ effects on MACE and/or hospitalisation for heart failure (HHF) and/or all-cause mortality in Type 2 diabetes mellitus (T2DM) patients.

METHODS

We systematically searched studies meeting inclusion criteria, compared design, methods and population characteristics, assessed risk for bias and did a meta-analysis (MA) using a random-effects model to calculate overall hazard ratios (HRs) and 95% CI (confidence intervals).

RESULTS

Sixteen studies included 285,436 T2DM patients exposed to GLP-1 RAs (exenatide bid, liraglutide, lixisenatide, long-acting exenatide), n ranged from 219 to 160,803 patients. Comparators included: no exposure, other antidiabetic medications (OADs), combined OADs, canagliflozin or multiple comparators. Ten studies estimated all-cause mortality, hazard ratios (HRs) ranged from 0.17 (95% CI 0.02-1.22) to 1.29 (95% CI 0.54-3.13). Thirteen studies assessed cardiovascular events and/or MACE; HRs ranged from 0.27 (95% CI 0.14-0.53) to 1.11 (95% CI 0.99-1.24). Eight studies assessed HHF, HRs ranged from 0.12 (95% CI 0.02-0.66) to 1.64 (95% CI 1.28-2.13). Excluding two studies because of temporal bias, we obtained pooled estimates for all-cause mortality: HR 0.63 (0.44-0.89), CV outcomes HR 0.84 (0.75-0.94) and HHF; HR 0.94 (0.78-1.14), (high between-study variability: I2 = 83.35%; I2 = 70.3%; and I2 = 90.1%, respectively).

CONCLUSION

Pooled results of EHDs' studies assessing GLP-1 RAs effects favoured GLP-1 RAs for all-cause mortality and MACE while were neutral for HHF. Results should be interpreted cautiously because of studies' substantial heterogeneity and limitations of observational research.

Authors+Show Affiliations

School of Medicine, Universidad Nacional de Córdoba, Córdoba, Argentina. Eu2P European Programme in Pharmacovigilance and Pharmacoepidemiology, University of Bordeaux Segalen, Bordeaux, France.Eu2P European Programme in Pharmacovigilance and Pharmacoepidemiology, University of Bordeaux Segalen, Bordeaux, France. Fundacio Institut Catala de Farmacologia, Universitat Autonoma de Barcelona, Barcelona, Spain.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32452094

Citation

Herrera Comoglio, Raquel, and Xavier Vidal Guitart. "Cardiovascular Outcomes, Heart Failure and Mortality in Type 2 Diabetic Patients Treated With Glucagon-like Peptide 1 Receptor Agonists (GLP-1 RAs): a Systematic Review and Meta-analysis of Observational Cohort Studies." International Journal of Clinical Practice, 2020, pp. e13553.
Herrera Comoglio R, Vidal Guitart X. Cardiovascular outcomes, heart failure and mortality in type 2 diabetic patients treated with glucagon-like peptide 1 receptor agonists (GLP-1 RAs): A systematic review and meta-analysis of observational cohort studies. Int J Clin Pract. 2020.
Herrera Comoglio, R., & Vidal Guitart, X. (2020). Cardiovascular outcomes, heart failure and mortality in type 2 diabetic patients treated with glucagon-like peptide 1 receptor agonists (GLP-1 RAs): A systematic review and meta-analysis of observational cohort studies. International Journal of Clinical Practice, e13553. https://doi.org/10.1111/ijcp.13553
Herrera Comoglio R, Vidal Guitart X. Cardiovascular Outcomes, Heart Failure and Mortality in Type 2 Diabetic Patients Treated With Glucagon-like Peptide 1 Receptor Agonists (GLP-1 RAs): a Systematic Review and Meta-analysis of Observational Cohort Studies. Int J Clin Pract. 2020 May 25;e13553. PubMed PMID: 32452094.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardiovascular outcomes, heart failure and mortality in type 2 diabetic patients treated with glucagon-like peptide 1 receptor agonists (GLP-1 RAs): A systematic review and meta-analysis of observational cohort studies. AU - Herrera Comoglio,Raquel, AU - Vidal Guitart,Xavier, Y1 - 2020/05/25/ PY - 2019/09/19/received PY - 2020/05/06/revised PY - 2020/05/18/accepted PY - 2020/5/27/pubmed PY - 2020/5/27/medline PY - 2020/5/27/entrez KW - all-cause mortality KW - electronic healthcare databases KW - glucagon-like peptide-1 receptor agonists KW - hospitalisation for heart failure KW - major adverse cardiovascular outcomes KW - type 2 diabetes mellitus SP - e13553 EP - e13553 JF - International journal of clinical practice JO - Int. J. Clin. Pract. N2 - BACKGROUND: Cardiovascular outcomes trials (CVOTs) have assessed the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on major adverse cardiovascular events (MACE) and mortality in high cardiovascular (CV) risk populations. Observational research can provide complementary evidence about these effects in unselected populations. AIM: To systematically review retrospective observational cohort studies conducted in electronic healthcare databases (EHDs) assessing GLP-1 RAs´ effects on MACE and/or hospitalisation for heart failure (HHF) and/or all-cause mortality in Type 2 diabetes mellitus (T2DM) patients. METHODS: We systematically searched studies meeting inclusion criteria, compared design, methods and population characteristics, assessed risk for bias and did a meta-analysis (MA) using a random-effects model to calculate overall hazard ratios (HRs) and 95% CI (confidence intervals). RESULTS: Sixteen studies included 285,436 T2DM patients exposed to GLP-1 RAs (exenatide bid, liraglutide, lixisenatide, long-acting exenatide), n ranged from 219 to 160,803 patients. Comparators included: no exposure, other antidiabetic medications (OADs), combined OADs, canagliflozin or multiple comparators. Ten studies estimated all-cause mortality, hazard ratios (HRs) ranged from 0.17 (95% CI 0.02-1.22) to 1.29 (95% CI 0.54-3.13). Thirteen studies assessed cardiovascular events and/or MACE; HRs ranged from 0.27 (95% CI 0.14-0.53) to 1.11 (95% CI 0.99-1.24). Eight studies assessed HHF, HRs ranged from 0.12 (95% CI 0.02-0.66) to 1.64 (95% CI 1.28-2.13). Excluding two studies because of temporal bias, we obtained pooled estimates for all-cause mortality: HR 0.63 (0.44-0.89), CV outcomes HR 0.84 (0.75-0.94) and HHF; HR 0.94 (0.78-1.14), (high between-study variability: I2 = 83.35%; I2 = 70.3%; and I2 = 90.1%, respectively). CONCLUSION: Pooled results of EHDs' studies assessing GLP-1 RAs effects favoured GLP-1 RAs for all-cause mortality and MACE while were neutral for HHF. Results should be interpreted cautiously because of studies' substantial heterogeneity and limitations of observational research. SN - 1742-1241 UR - https://www.unboundmedicine.com/medline/citation/32452094/Cardiovascular_outcomes,_heart_failure_and_mortality_in_Type_2_diabetic_patients_treated_with_glucagon-like_peptide_1_receptor_agonists_(GLP-1_RAs):_a_systematic_review_and_meta-analysis_of_observational_cohort_studies L2 - https://doi.org/10.1111/ijcp.13553 DB - PRIME DP - Unbound Medicine ER -
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