The safe use of metformin in heart failure patients both with and without T2DM: A cross-sectional and longitudinal study

Gina Chowdhury^{1

2}, Jane E Carland^{1

3}, Shaun Kumar⁴, Nick Olsen⁵, Garry Graham^{1

3}, Gayathri Kumarasinghe^{6

7

8}, Christopher S Hayward^{3

6

7}, Jerry R Greenfield^{3

9

10}, Peter Macdonald^{3

6

7}, Richard O Day^{1

3}, Sophie L Stocker^{1

3

11}

Affiliations

¹ Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital Sydney, Sydney, Australia.
² School of Medical Science, The University of New South Wales, Sydney, Australia.
³ School of Clinical Medicine, UNSW Medicine & Health, St Vincent's Healthcare Clinical Campus, University of New South Wales, Sydney, Australia.
⁴ Clinical Pharmacology, Modelling and Simulation, Parexel International, Sydney, Australia.
⁵ School of Mathematics and Statistics, The University of New South Wales, Sydney, Australia.
⁶ Heart & Lung Transplant Unit, St Vincent's Hospital Sydney, Sydney, Australia.
⁷ Victor Chang Cardiac Research Institute, Sydney, Australia.
⁸ Department of Cardiology, Liverpool Hospital, Sydney, Australia.
⁹ Department of Endocrinology, St Vincent's Hospital Sydney, Sydney, Australia.
¹⁰ Garvan Institute of Medical Research, Sydney, Australia.
¹¹ School of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.

PMID: 37016750
DOI: 10.1111/bcp.15737

Free article

The safe use of metformin in heart failure patients both with and without T2DM: A cross-sectional and longitudinal study

Gina Chowdhury et al. Br J Clin Pharmacol. 2023 Aug.

Free article

. 2023 Aug;89(8):2603-2613.

doi: 10.1111/bcp.15737. Epub 2023 Apr 25.

Authors

Affiliations

¹ Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital Sydney, Sydney, Australia.
² School of Medical Science, The University of New South Wales, Sydney, Australia.
³ School of Clinical Medicine, UNSW Medicine & Health, St Vincent's Healthcare Clinical Campus, University of New South Wales, Sydney, Australia.
⁴ Clinical Pharmacology, Modelling and Simulation, Parexel International, Sydney, Australia.
⁵ School of Mathematics and Statistics, The University of New South Wales, Sydney, Australia.
⁶ Heart & Lung Transplant Unit, St Vincent's Hospital Sydney, Sydney, Australia.
⁷ Victor Chang Cardiac Research Institute, Sydney, Australia.
⁸ Department of Cardiology, Liverpool Hospital, Sydney, Australia.
⁹ Department of Endocrinology, St Vincent's Hospital Sydney, Sydney, Australia.
¹⁰ Garvan Institute of Medical Research, Sydney, Australia.
¹¹ School of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.

PMID: 37016750
DOI: 10.1111/bcp.15737

Abstract

Aims: This study investigated the safe use of metformin in patients with (1) type 2 diabetes mellitus (T2DM) and heart failure on metformin, and (2) heart failure without T2DM and metformin naïve.

Methods: Two prospective studies on heart failure patients were undertaken. The first was a cross-sectional study with two patient cohorts, one with T2DM on metformin (n = 44) and one without T2DM metformin naive (n = 47). The second was a 12-week interventional study of patients without T2DM (n = 27) where metformin (500 mg immediate release, twice daily) was prescribed. Plasma metformin and lactate concentrations were monitored. Individual pharmacokinetics were compared between cohorts. Univariable and multivariable analysis analysed the effects of variables on plasma lactate concentrations.

Results: Plasma metformin and lactate concentrations mostly (99.9%) remained below safety thresholds (5 mg/L and 5 mmol/L, respectively). Metformin concentration had no significant relationship with lactic acidosis safety markers. In the interventional study, New York Heart Association (NYHA) II (P < .03) and III (P < .001) grading was associated with higher plasma lactate concentrations, whereas male sex was associated with 47% higher plasma lactate concentrations (P < .05). The pharmacokinetics of heart failure patients with and without T2DM were similar.

Conclusions: We observed no unsafe plasma lactate concentrations in patients with heart failure treated with metformin. Metformin exposure did not influence plasma lactate concentrations, but NYHA class and sex did. The pharmacokinetics of metformin in heart failure patients are similar irrespective of T2DM. These findings may support the safe use of metformin in heart failure patients with and without T2DM.

Keywords: diabetes; drug safety; heart failure; pharmacokinetics.

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References

REFERENCES

1. Andersson C, Olesen JB, Hansen PR, et al. Metformin treatment is associated with a low risk of mortality in diabetic patients with heart failure: a retrospective nationwide cohort study. Diabetologia. 2010;53(12):2546-2553. doi:10.1007/s00125-010-1906-6
1. Aguilar D, Chan W, Bozkurt B, Ramasubbu K, Deswal A. Metformin use and mortality in ambulatory patients with diabetes and heart failure. Circ Heart Fail. 2011;4(1):53-58. doi:10.1161/CIRCHEARTFAILURE.110.952556
1. Hirst JA, Farmer AJ, Ali R, Roberts NW, Stevens RJ. Quantifying the effect of metformin treatment and dose on glycemic control. Diabetes Care. 2012;35(2):446-454. doi:10.2337/dc11-1465
1. Rodbard HW, Jellinger PS, Davidson JA, et al. Statement by an American association of clinical endocrinologists/American college of endocrinology consensus panel on type 2 diabetes mellitus. An algorithm for glycemic control. Endocr Pract. 2009;15(6):540-559. doi:10.4158/ep.15.6.540
1. UK Prospective Diabetes Study (UKPDS) Group. UKPDS. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352(9131):854-865. doi:10.1016/S0140-6736(98)07037-8

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The safe use of metformin in heart failure patients both with and without T2DM: A cross-sectional and longitudinal study

Affiliations

The safe use of metformin in heart failure patients both with and without T2DM: A cross-sectional and longitudinal study

Authors

Affiliations

Abstract

References

REFERENCES

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical