Skip to main content

Advertisement

SpringerLink
Log in

Impact of Heart Failure History at Baseline on Cardiovascular Effects of GLP-1 Receptor Agonists in Type 2 Diabetes: a Meta-analysis

  • Short Communication
  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Abstract

Purpose

Effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in type-2 diabetes mellitus (T2DM) with or without prior heart failure (HF) have been inconsistent across cardiovascular outcome trials. This study aimed to investigate the impact of HF history at baseline on cardiovascular effects of GLP-1 RAs in T2DM.

Methods

PubMed, Embase, Web of Science, and clinical trial registries were searched for randomized controlled trials (RCTs) or post hoc analyses (≥ 24 weeks) reporting HF hospitalizations and/or cardiovascular death (HHF/CVD), major adverse cardiovascular events (MACE) comprising of cardiovascular death, myocardial infarction, and stroke in adults with T2DM with or without HF history (PROSPERO:CRD42022367633). Hazard ratios (HRs) in GLP-1RAs versus placebo arms were pooled together using the generic inverse variance method in fixed-effects model. Subgroup analysis was performed.

Results

We identified 5 eligible studies, pooling data retrieved from six RCTs and 48,489 individuals with T2DM. On pooled analysis, GLP1RA treatment versus placebo significantly reduced risk of HHF/CVD in only T2DM without HF history (HR = 0.84; 95%CI, 0.77–0.91; I2 = 14%; p < 0.001), but not in those with HF history (HR = 0.96; 95%CI, 0.85–1.08; I2 = 14%; p = 0.4) (p-interaction < 0.1). GLP-1RAs reduced incident HHF in T2DM with or without HF history (HR = 0.89; 95%CI, 0.80–0.98; I2 = 41%; p < 0.05) (p-interaction = 0.28). Sensitivity analysis excluding REWIND trial accentuated the impact of baseline HF history on both HHF/CVD and HHF (p-interaction < 0.05). Benefits on MACE with GLP-1RAs were consistently seen in T2DM regardless of HF history (p-interaction = 0.8).

Conclusion

GLP-1RAs consistently prevented HF hospitalizations and MACE in T2DM regardless of baseline HF history, whereas significant attenuation of benefits on composite HHF/CV death were observed in those with HF history.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Data Availability

Not applicable.

Code Availability

Not applicable.

Abbreviations

EXSCEL trial:

Exenatide Study of Cardiovascular Event Lowering trial

HARMONY OUTCOMES:

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease

LEADER:

Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results

REWIND:

Researching Cardiovascular Events with a Weekly Incretin (Dulaglutide) in Diabetes

SUSTAIN-6:

Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes

PIONEER-6:

Peptide Innovation (oral Semaglutide) for Early Diabetes Treatment

References

  1. Pop-Busui R, Januzzi JL, Bruemmer D, et al. Heart failure: an underappreciated complication of diabetes. A Consensus Report of the American Diabetes Association. Diabetes Care. 2022;45:1670–90.

    Article  Google Scholar 

  2. Kenny HC, Abel ED. Heart failure in type 2 diabetes mellitus: impact of glucose-lowering agents, heart failure therapies, and novel therapeutic strategies. Circ Res. 2019;124:121–41.

    Article  CAS  Google Scholar 

  3. Davies MJ, Aroda VR, Collins BS, et al. Management of hyperglycemia in type 2 diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2022;dci220034.

  4. Margulies KB, Hernandez AF, Redfield MM, et al. Effects of liraglutide on clinical stability among patients with advanced heart failure and reduced ejection fraction: a randomized clinical trial. JAMA. 2016;316:500.

    Article  CAS  Google Scholar 

  5. Jorsal A, Kistorp C, Holmager P, et al. Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes ( LIVE )—a multicentre, double-blind, randomised, placebo-controlled trial. Eur J Heart Fail. 2017;19:69–77.

    Article  CAS  Google Scholar 

  6. Fudim M, White J, Pagidipati NJ, et al. Effect of once-weekly exenatide in patients with type 2 diabetes mellitus with and without heart failure and heart failure–related outcomes: insights from the EXSCEL trial. Circulation. 2019;140:1613–22.

    Article  CAS  Google Scholar 

  7. Ferreira JP, Sharma A, Vasques-Nóvoa F, et al. Albiglutide in patients with type 2 diabetes and heart failure: a post-hoc analysis from Harmony Outcomes. Eur J Heart. 2022;Fail ejhf.2660.

  8. Marso SP, Baeres FMM, Bain SC, et al. Effects of liraglutide on cardiovascular outcomes in patients with diabetes with or without heart failure. J Am Coll Cardiol. 2020;75:1128–41.

    Article  CAS  Google Scholar 

  9. Branch KRH, Dagenais GR, Avezum A, et al. Dulaglutide and cardiovascular and heart failure outcomes in patients with and without heart failure: a post-hoc analysis from the rewind randomized trial. Eur J Heart Fail. 2022;ejhf.2670.

  10. Husain M, Bain SC, Jeppesen OK, et al. Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk. Diabetes Obes Metab. 2020;22:442–51.

    Article  Google Scholar 

  11. Sattar N, Lee MMY, Kristensen SL, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials. Lancet Diabetes Endocrinol. 2021;9:653–62.

    Article  CAS  Google Scholar 

  12. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700–b2700.

    Article  Google Scholar 

  13. Richardson M, Garner P, Donegan S. Interpretation of subgroup analyses in systematic reviews: a tutorial. Clin Epidemiol Glob Health. 2019;7:192–8.

    Article  Google Scholar 

  14. Nichols GA, Hillier TA, Erbey JR, Brown JB. Congestive heart failure in type 2 diabetes. Diabetes Care. 2001;24:1614–9.

    Article  CAS  Google Scholar 

  15. Neves JS, Vasques-Nóvoa F, Borges-Canha M, et al. Risk of adverse events with liraglutide in heart failure with reduced ejection fraction: a post hoc analysis of the FIGHT trial. Diabetes Obes Metab dom. 2022;14862.

Download references

Author information

Authors and Affiliations

  1. Department of Endocrinology, Institute of Postgraduate Medical Education and Research, Kolkata, 700020, India

    Mainak Banerjee, Indira Maisnam & Satinath Mukhopadhyay

Authors
  1. Mainak Banerjee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Indira Maisnam
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Satinath Mukhopadhyay
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

M. B. is the primary author and the guarantor of work done. M. B. and I. M. had performed literature search and data extraction. Formal analysis was performed by M. B. S. M. edited the manuscript. All the authors approved the final version of the manuscript.

Corresponding author

Correspondence to Mainak Banerjee.

Ethics declarations

Ethics Approval

Not applicable.

Consent to Participate

Not applicable since this study used already published data.

Consent for Publication

Not applicable.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 96 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Banerjee, M., Maisnam, I. & Mukhopadhyay, S. Impact of Heart Failure History at Baseline on Cardiovascular Effects of GLP-1 Receptor Agonists in Type 2 Diabetes: a Meta-analysis. Cardiovasc Drugs Ther (2023). https://doi.org/10.1007/s10557-023-07432-5

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10557-023-07432-5

Keywords

Search

Navigation