Can glucose-lowering medications improve outcomes in non-diabetic heart failure patients? A Bayesian network meta-analysis - PubMed (original) (raw)

. 2022 Apr;9(2):1338-1350.

doi: 10.1002/ehf2.13822. Epub 2022 Jan 29.

Aaron Shengting Mai 1, Oliver Z H Lim 1, Cheng Han Ng 1, Yip Han Chin 1, Phoebe Tay 1, Chaoxing Lin 1, Mark Muthiah 1 2, Chin Meng Khoo 3, Mayank Dalakoti 4, Poay-Huan Loh 1 4, Mark Chan 1 4, Tiong-Cheng Yeo 1 4, Roger Foo 1 4, Raymond Wong 1 4, Nicholas W S Chew 4, Weiqin Lin 1 4

Affiliations

Can glucose-lowering medications improve outcomes in non-diabetic heart failure patients? A Bayesian network meta-analysis

Trevor Yeong et al. ESC Heart Fail. 2022 Apr.

Abstract

Aims: The cardioprotective effects of glucose-lowering medications in diabetic patients with heart failure (HF) are well known. Several large randomized controlled trials (RCTs) have recently suggested that the cardioprotective effects of glucose-lowering medications extend to HF patients regardless of diabetic status. The aim of this study was to conduct a Bayesian network meta-analysis to evaluate the impact of various glucose-lowering medications on the outcomes of non-diabetic HF patients.

Methods and results: Medline and Embase were searched for RCTs investigating the use of glucose-lowering medications in non-diabetic HF patients in August 2021. Studies were included in accordance with the inclusion and exclusion criteria, and data were extracted with a pre-defined datasheet. Primary outcomes include serum N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels, left ventricular ejection fraction (LVEF), and maximal oxygen consumption (PVO2 ). A Bayesian network meta-analysis was performed to compare the effectiveness of different classes of glucose-lowering medications in improving HF outcomes. Risk-of-bias was assessed using Cochrane Risk-of-Bias tool 2.0 for randomized trials (ROB2). Seven RCTs involving 2897 patients were included. Sodium-glucose transporter 2 inhibitor (SGLT2i) was the most favourable in lowering NT-proBNP, with the significant reduction in NT-proBNP when compared with glucagon-like peptide-1 receptor agonists (GLP1-RA) [mean differences (MD): -229.59 pg/mL, 95%-credible intervals (95%-CrI): -238.31 to -220.91], metformin (MD: -237.15 pg/mL, 95%-CrI: -256.19 to -218.14), and placebo (MD: -228.00 pg/mL, 95%-CrI: -233.99 to -221.99). SGLT2i was more effective in improving LVEF for HF with reduced ejection fraction patients relative to GLP1-RA (MD: 8.09%, 95%-CrI: 6.30 to 9.88) and placebo (MD: 6.10%, 95%-CrI: 4.37 to 7.84). SGLT2i and GLP1-RA were more favourable to placebo in improving PVO2 , with significant increase of PVO2 at a MD of 1.60 mL/kg/min (95%-CrI: 0.63 to 2.57) and 0.86 mL/kg/min (95%-CrI: 0.66 to 1.06), respectively. All three drugs had comparable safety profiles when compared with placebo.

Conclusions: This Bayesian network meta-analysis demonstrated that SGLT2i, when compared with GLP1-RA and metformin, was superior in improving LVEF in HF with reduced ejection fraction patients, as well as improving PVO2 and NT-proBNP in non-diabetic HF patients. Further large-scale prospective studies are needed to confirm these preliminary findings.

Keywords: Glucagon-like peptide 1 receptor agonists; Heart failure; Metformin; Sodium-glucose cotransporter 2 inhibitors.

© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

PubMed Disclaimer

Conflict of interest statement

All authors declare that they have no conflicts of interest.

Figures

Figure 1

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta‐Analyses flow diagram. RCTs, randomized controlled trials.

Figure 2

Figure 2

Traffic light plot for the risk‐of‐bias assessment of included trials.

Figure 3

Figure 3

Comparison of changes in serum NT‐proBNP levels. League table heatmap. The values in each cell represent the relative treatment effect (95%‐CI) of the treatment on the top compared with the treatment on the left. NT‐proBNP, N‐terminal prohormone of brain natriuretic peptide.

Figure 4

Figure 4

Comparison of changes in left ventricular ejection fraction. League table heatmap. The values in each cell represent the relative treatment effect (95%‐CI) of the treatment on the top compared with the treatment on the left. LVEF, left ventricular ejection fraction.

Figure 5

Figure 5

Comparison of changes in maximal oxygen consumption. League table heatmap. The values in each cell represent the relative treatment effect (95%‐CI) of the treatment on the top compared with the treatment on the left.

References

    1. McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, Böhm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukát A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O'Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjöstrand M, Langkilde AM. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med 2019; 381: 1995–2008. - PubMed
    1. Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, Januzzi J, Verma S, Tsutsui H, Brueckmann M, Jamal W, Kimura K, Schnee J, Zeller C, Cotton D, Bocchi E, Böhm M, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Janssens S, Zhang J, Gonzalez Juanatey JR, Kaul S, Brunner‐la Rocca HP, Merkely B, Nicholls SJ, Perrone S, Pina I, Ponikowski P, Sattar N, Senni M, Seronde MF, Spinar J, Squire I, Taddei S, Wanner C, Zannad F. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med 2020; 383: 1413–1424. - PubMed
    1. Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M, Brunner‐la Rocca HP, Choi DJ, Chopra V, Chuquiure‐Valenzuela E, Giannetti N, Gomez‐Mesa JE, Janssens S, Januzzi JL, Gonzalez‐Juanatey JR, Merkely B, Nicholls SJ, Perrone SV, Piña IL, Ponikowski P, Senni M, Sim D, Spinar J, Squire I, Taddei S, Tsutsui H, Verma S, Vinereanu D, Zhang J, Carson P, Lam CSP, Marx N, Zeller C, Sattar N, Jamal W, Schnaidt S, Schnee JM, Brueckmann M, Pocock SJ, Zannad F, Packer M, EMPEROR‐Preserved Trial Investigators . Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med 2021; 385: 1451–1461. - PubMed
    1. Zinman B, Lachin JM, Inzucchi SE. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2016; 374: 1094. - PubMed
    1. Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017; 377: 644–657. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources