PMID- 34944478 OWN - NLM STAT- MEDLINE DCOM- 20220113 LR - 20220113 IS - 2218-273X (Electronic) IS - 2218-273X (Linking) VI - 11 IP - 12 DP - 2021 Dec 4 TI - Effects of Metformin in Heart Failure: From Pathophysiological Rationale to Clinical Evidence. LID - 10.3390/biom11121834 [doi] LID - 1834 AB - Type 2 diabetes mellitus (T2DM) is a worldwide major health burden and heart failure (HF) is the most common cardiovascular (CV) complication in affected patients. Therefore, identifying the best pharmacological approach for glycemic control, which is also useful to prevent and ameliorate the prognosis of HF, represents a crucial issue. Currently, the choice is between the new drugs sodium/glucose co-transporter 2 inhibitors that have consistently shown in large CV outcome trials (CVOTs) to reduce the risk of HF-related outcomes in T2DM, and metformin, an old medicament that might end up relegated to the background while exerting interesting protective effects on multiple organs among which include heart failure. When compared with other antihyperglycemic medications, metformin has been demonstrated to be safe and to lower morbidity and mortality for HF, even if these results are difficult to interpret as they emerged mainly from observational studies. Meta-analyses of randomized controlled clinical trials have not produced positive results on the risk or clinical course of HF and sadly, large CV outcome trials are lacking. The point of force of metformin with respect to new diabetic drugs is the amount of data from experimental investigations that, for more than twenty years, still continues to provide mechanistic explanations of the several favorable actions in heart failure such as, the improvement of the myocardial energy metabolic status by modulation of glucose and lipid metabolism, the attenuation of oxidative stress and inflammation, and the inhibition of myocardial cell apoptosis, leading to reduced cardiac remodeling and preserved left ventricular function. In the hope that specific large-scale trials will be carried out to definitively establish the metformin benefit in terms of HF failure outcomes, we reviewed the literature in this field, summarizing the available evidence from experimental and clinical studies reporting on effects in heart metabolism, function, and structure, and the prominent pathophysiological mechanisms involved. FAU - Salvatore, Teresa AU - Salvatore T AD - Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via De Crecchio 7, I-80138 Naples, Italy. FAU - Galiero, Raffaele AU - Galiero R AUID- ORCID: 0000-0002-7766-3430 AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, I-80138 Naples, Italy. FAU - Caturano, Alfredo AU - Caturano A AUID- ORCID: 0000-0001-7761-7533 AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, I-80138 Naples, Italy. FAU - Vetrano, Erica AU - Vetrano E AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, I-80138 Naples, Italy. FAU - Rinaldi, Luca AU - Rinaldi L AUID- ORCID: 0000-0002-6541-3821 AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, I-80138 Naples, Italy. FAU - Coviello, Francesca AU - Coviello F AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, I-80138 Naples, Italy. FAU - Di Martino, Anna AU - Di Martino A AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, I-80138 Naples, Italy. FAU - Albanese, Gaetana AU - Albanese G AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, I-80138 Naples, Italy. FAU - Marfella, Raffaele AU - Marfella R AUID- ORCID: 0000-0003-3960-9270 AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, I-80138 Naples, Italy. FAU - Sardu, Celestino AU - Sardu C AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, I-80138 Naples, Italy. FAU - Sasso, Ferdinando Carlo AU - Sasso FC AUID- ORCID: 0000-0002-9142-7848 AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, I-80138 Naples, Italy. LA - eng PT - Journal Article PT - Review DEP - 20211204 PL - Switzerland TA - Biomolecules JT - Biomolecules JID - 101596414 RN - 9100L32L2N (Metformin) SB - IM MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Heart Failure/etiology/*prevention & control MH - Humans MH - Metformin/pharmacology/*therapeutic use MH - Randomized Controlled Trials as Topic PMC - PMC8698925 OTO - NOTNLM OT - heart failure OT - metformin OT - type 2 diabetes COIS- The authors declare no conflict of interest. EDAT- 2021/12/25 06:00 MHDA- 2022/01/14 06:00 PMCR- 2021/12/04 CRDT- 2021/12/24 01:05 PHST- 2021/10/26 00:00 [received] PHST- 2021/11/26 00:00 [revised] PHST- 2021/12/01 00:00 [accepted] PHST- 2021/12/24 01:05 [entrez] PHST- 2021/12/25 06:00 [pubmed] PHST- 2022/01/14 06:00 [medline] PHST- 2021/12/04 00:00 [pmc-release] AID - biom11121834 [pii] AID - biomolecules-11-01834 [pii] AID - 10.3390/biom11121834 [doi] PST - epublish SO - Biomolecules. 2021 Dec 4;11(12):1834. doi: 10.3390/biom11121834.