The safe use of metformin in heart failure patients both with and without T2DM: A cross-sectional and longitudinal study.
Chowdhury, G
Carland, JE
Kumar, S
Olsen, N
Graham, G
Kumarasinghe, G
Hayward, CS
Greenfield, JR
Macdonald, P
Day, RO
Stocker, SL
- Publisher:
- Wiley
- Publication Type:
- Journal Article
- Citation:
- Br J Clin Pharmacol, 2023, 89, (8), pp. 2603-2613
- Issue Date:
- 2023-08
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Chowdhury, G | |
dc.contributor.author | Carland, JE | |
dc.contributor.author | Kumar, S | |
dc.contributor.author | Olsen, N | |
dc.contributor.author | Graham, G | |
dc.contributor.author | Kumarasinghe, G | |
dc.contributor.author | Hayward, CS | |
dc.contributor.author | Greenfield, JR | |
dc.contributor.author |
Macdonald, P https://orcid.org/0000-0001-5378-2825 |
|
dc.contributor.author | Day, RO | |
dc.contributor.author | Stocker, SL | |
dc.date.accessioned | 2024-04-09T22:42:45Z | |
dc.date.available | 2023-03-25 | |
dc.date.available | 2024-04-09T22:42:45Z | |
dc.date.issued | 2023-08 | |
dc.identifier.citation | Br J Clin Pharmacol, 2023, 89, (8), pp. 2603-2613 | |
dc.identifier.issn | 0306-5251 | |
dc.identifier.issn | 1365-2125 | |
dc.identifier.uri | http://hdl.handle.net/10453/177632 | |
dc.description.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. | |
dc.format | Print-Electronic | |
dc.language | eng | |
dc.publisher | Wiley | |
dc.relation.ispartof | Br J Clin Pharmacol | |
dc.relation.isbasedon | 10.1111/bcp.15737 | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | 1115 Pharmacology and Pharmaceutical Sciences | |
dc.subject.classification | Pharmacology & Pharmacy | |
dc.subject.classification | 3214 Pharmacology and pharmaceutical sciences | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Male | |
dc.subject.mesh | Metformin | |
dc.subject.mesh | Diabetes Mellitus, Type 2 | |
dc.subject.mesh | Cross-Sectional Studies | |
dc.subject.mesh | Hypoglycemic Agents | |
dc.subject.mesh | Longitudinal Studies | |
dc.subject.mesh | Prospective Studies | |
dc.subject.mesh | Lactic Acid | |
dc.subject.mesh | Heart Failure | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Diabetes Mellitus, Type 2 | |
dc.subject.mesh | Metformin | |
dc.subject.mesh | Lactic Acid | |
dc.subject.mesh | Hypoglycemic Agents | |
dc.subject.mesh | Longitudinal Studies | |
dc.subject.mesh | Prospective Studies | |
dc.subject.mesh | Cross-Sectional Studies | |
dc.subject.mesh | Male | |
dc.subject.mesh | Heart Failure | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Male | |
dc.subject.mesh | Metformin | |
dc.subject.mesh | Diabetes Mellitus, Type 2 | |
dc.subject.mesh | Cross-Sectional Studies | |
dc.subject.mesh | Hypoglycemic Agents | |
dc.subject.mesh | Longitudinal Studies | |
dc.subject.mesh | Prospective Studies | |
dc.subject.mesh | Lactic Acid | |
dc.subject.mesh | Heart Failure | |
dc.title | The safe use of metformin in heart failure patients both with and without T2DM: A cross-sectional and longitudinal study. | |
dc.type | Journal Article | |
utslib.citation.volume | 89 | |
utslib.location.activity | England | |
utslib.for | 1115 Pharmacology and Pharmaceutical Sciences | |
pubs.organisational-group | University of Technology Sydney | |
pubs.organisational-group | University of Technology Sydney/Faculty of Health | |
utslib.copyright.status | open_access | * |
dc.date.updated | 2024-04-09T22:42:44Z | |
pubs.issue | 8 | |
pubs.publication-status | Published | |
pubs.volume | 89 | |
utslib.citation.issue | 8 |
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.
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