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Type 2 diabetes and risk of heart failure: a systematic review and meta-analysis from cardiovascular outcome trials

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Abstract

Aim

We performed a meta-analysis of randomized controlled trials (RCTs) that evaluated the effect of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium glucose co-transporter-2 inhibitors (SGLT-2i) on heart failure (HF) risk in patients with type 2 diabetes (T2D).

Methods and results

The electronic search was carried out until 10 November 2018. RCTs were included if they compared add-on therapy with any DPP-4i, GLP-1 RAs, or SGLT-2i with placebo, and included in the outcome hospitalization for HF, and other outcomes required for cardiovascular safety studies. Risk of HF was the primary outcome for this meta-analysis. We used a random-effect model to calculate hazard ratio (HR) and 95% CI. Twelve trials were identified, involving 120,765 patients. Compared with placebo, HF risk showed a non-significant 10% reduction with the newer anti-hyperglycemic drugs (HR = 0.90, 0.80–1.01); use of DPP-4i and GLP-1 RAs was associated with nonsignificant modifications of the HF risk (+5% and −9%, respectively), while the use of SGLT-2i was associated with a significant 31% reduction of the HF risk (HR = 0.69, 0.61–0.79, P < 0.001), with no heterogeneity (I2 = 0%, P = 0.741), suggesting a class effect. The meta-regression analysis of all 12 trials showed no association of reductions of hemoglobin A1C with HF risk.

Conclusion

In T2D, SGLT-2i can reduce the risk of HF that is unrelated to improved glycemic control; DPP-4i and GLP-1 RAs behave as neutral.

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Acknowledgements

D.G. is the guarantor of this article.

Funding

This research was supported in part by the “Associazione Salute con Stile”, Naples, Italy.

Author contributions

D.G., M.I.M., and M.L. conducted the literature search, data extraction, and data analysis. P.C. and D.G. did the statistical analyses. G.B. contributed to the data analysis and to writing the manuscript. K.E. and D.G. wrote, reviewed, and edited the manuscript. All the authors approved the final version of the manuscript.

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Author notes

  1. These authors share last authorship: Paolo Chiodini, Katherine Esposito

Authors and Affiliations

  1. Division of Endocrinology and Metabolic Diseases, Department of Advanced Medical and Surgical Sciences, Università della Campania L. Vanvitelli, Naples, Italy

    Dario Giugliano, Maria Ida Maiorino & Giuseppe Bellastella

  2. Medical Statistics Unit, Università della Campania L. Vanvitelli, Naples, Italy

    Miriam Longo & Paolo Chiodini

  3. Diabetes Unit, Department of Advanced Medical and Surgical Sciences, Università della Campania L. Vanvitelli, Naples, Italy

    Katherine Esposito

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  1. Dario Giugliano
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Correspondence to Dario Giugliano.

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Conflict of interest

D.G. received honoraria for speaking at meetings from Novartis, Sanofi-Aventis, Lilly, AstraZeneca, and Novo Nordisk. K.E. received honoraria for speaking at meetings from Novartis, Sanofi-Aventis, Lilly, AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. M.I.M. received honoraria for speaking at meetings from Lilly and Novo Nordisk. The other authors declare that they have no conflict of interest.

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Giugliano, D., Maiorino, M.I., Longo, M. et al. Type 2 diabetes and risk of heart failure: a systematic review and meta-analysis from cardiovascular outcome trials. Endocrine 65, 15–24 (2019). https://doi.org/10.1007/s12020-019-01931-y

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