Glucagon-like peptide-1 receptor agonists and heart failure in type 2 diabetes: systematic review and meta-analysis of randomized and observational studies

Ling Li; Sheyu Li; Jiali Liu; Ke Deng; Jason W Busse; Per Olav Vandvik; Evelyn Wong; Zahra N Sohani; Malgorzata M Bala; Lorena P Rios; German Malaga; Shanil Ebrahim; Jiantong Shen; Longhao Zhang; Pujing Zhao; Qunfei Chen; Yingqiang Wang; Gordon H Guyatt; Xin Sun

doi:10.1186/s12872-016-0260-0

Glucagon-like peptide-1 receptor agonists and heart failure in type 2 diabetes: systematic review and meta-analysis of randomized and observational studies

BMC Cardiovasc Disord. 2016 May 11:16:91. doi: 10.1186/s12872-016-0260-0.

Authors

Ling Li¹, Sheyu Li², Jiali Liu¹, Ke Deng³, Jason W Busse^{4

5

6}, Per Olav Vandvik^{7

8}, Evelyn Wong⁹, Zahra N Sohani^{4

10}, Malgorzata M Bala^{11

12}, Lorena P Rios¹³, German Malaga¹⁴, Shanil Ebrahim^{4

5

15

16}, Jiantong Shen¹, Longhao Zhang¹, Pujing Zhao¹, Qunfei Chen¹⁷, Yingqiang Wang¹⁸, Gordon H Guyatt^{4

19}, Xin Sun²⁰

Affiliations

¹ Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, 37 GuoXue Xiang, Chengdu, 610041, Sichuan, China.
² Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
³ West China school of Pharmacy, Sichuan University, Chengdu, Sichuan, China.
⁴ Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
⁵ Department of Anesthesia, McMaster University, Hamilton, ON, Canada.
⁶ The Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, ON, Canada.
⁷ Norwegian Knowledge Centre for the Health Services, Oslo, Norway.
⁸ Department of Medicine, Innlandet Hospital Trust, Gjøvik, Norway.
⁹ Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
¹⁰ Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, ON, Canada.
¹¹ Department of Hygiene and Dietetics, Jagiellonian University Medical College, Krakow, Poland.
¹² Systematic Reviews Unit-Polish Cochrane Branch, Jagiellonian University Medical College, Krakow, Poland.
¹³ Internal Medicine Unit, Hospital Clinico FUSAT, Rancagua, Chile.
¹⁴ Department of Medicine, Universidad Peruana Cayetano Heredia, Lima, Peru.
¹⁵ Stanford Prevention Research Center, Department of Medicine, Stanford University, Stanford, USA.
¹⁶ Department of Anaesthesia & Pain Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
¹⁷ The Second Hospital of Lanzhou University, Lanzhou, China.
¹⁸ Department of Medical Administration, 363 Hospital, Chengdu, Sichuan, China.
¹⁹ Department of Medicine, McMaster University, Hamilton, ON, Canada.
²⁰ Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, 37 GuoXue Xiang, Chengdu, 610041, Sichuan, China. sunx79@hotmail.com.

Abstract

Background: The effect of glucagon-like peptide-1(GLP-1) receptor agonists on heart failure remains uncertain. We therefore conducted a systematic review to assess the possible impact of GLP-1 agonists on heart failure or hospitalization for heart failure in patients with type 2 diabetes.

Methods: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov to identify randomized controlled trials (RCTs) and observational studies that addressed the effect of GLP-1 receptor agonists in adults with type 2 diabetes, and explicitly reported heart failure or hospitalization for heart failure. Two paired reviewers screened reports, collected data, and assessed the risk of bias. We pooled data from RCTs and observational studies separately, and used the GRADE approach to rate the quality of evidence.

Results: We identified 25 studies that were eligible for our review; 21 RCTs (n = 18,270) and 4 observational studies (n = 111,029). Low quality evidence from 20 RCTs suggested, if anything, a lower incidence of heart failure between GLP-1 agonists versus control (17/7,441 vs. 19/4,317; odds ratio (OR) 0.62, 95 % confidence interval (CI) 0.31 to 1.22; risk difference (RD) 19 fewer, 95 % CI 34 fewer to 11 more per 1000 over 5 years). Three cohort studies comparing GLP-1 agonists to alternative agents provided very low quality evidence that GLP-1 agonists do not increase the incidence of heart failure. One RCT provided moderate quality evidence that GLP-1 agonists were not associated with hospitalization for heart failure (lixisenatide vs placebo: 122/3,034 vs. 127/3,034; adjusted hazard ratio 0.96, 95 % CI 0.75 to 1.23; RD 4 fewer, 95 % CI 25 fewer to 23 more per 1000 over 5 years) and a case-control study provided very low quality evidence also suggesting no association (GLP-1 agonists vs. other anti-hyperglycemic drugs: 1118 cases and 17,626 controls, adjusted OR 0.67, 95 % CI 0.32 to 1.42).

Conclusions: The current evidence suggests that GLP-1 agonists do not increase the risk of heart failure or hospitalization for heart failure among patients with type 2 diabetes.

Keywords: Glucagon-like peptide-1 receptor; Heart failure; Meta-analysis; Systematic review; Type 2 diabetes.

Publication types

Meta-Analysis
Review
Systematic Review

MeSH terms

Animals
Chi-Square Distribution
Diabetes Mellitus, Type 2 / complications
Diabetes Mellitus, Type 2 / diagnosis
Diabetes Mellitus, Type 2 / drug therapy*
Diabetes Mellitus, Type 2 / mortality
Glucagon-Like Peptide-1 Receptor / agonists*
Glucagon-Like Peptide-1 Receptor / metabolism
Heart Failure / diagnosis
Heart Failure / etiology*
Heart Failure / mortality
Hospitalization
Humans
Hypoglycemic Agents / adverse effects
Hypoglycemic Agents / therapeutic use*
Observational Studies as Topic
Odds Ratio
Randomized Controlled Trials as Topic
Risk Assessment
Risk Factors
Time Factors
Treatment Outcome

Substances

Glucagon-Like Peptide-1 Receptor
Hypoglycemic Agents