Possible role of metformin as an antidepressant in diabetes

• Published in: Journal of affective disorders Vol. 351; pp. 349 - 355
• Main Authors: Pedreañez, Adriana, Carrero, Yenddy, Vargas, Renata, Hernandez-Fonseca, Juan P., Mosquera-Sulbaran, Jesús
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.04.2024
• Subjects: Angiotensin II; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antidepressive Agents - pharmacology; Antidepressive Agents - therapeutic use; Depression, diabetes; Diabetes Mellitus, Type 2 - drug therapy; Humans; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Inflammation - drug therapy; Insulin; Insulin - therapeutic use; Lipopolysaccharides; Metformin; Metformin - pharmacology; Metformin - therapeutic use; Microbiota; Microbiota; Metformin; Depression, diabetes; Angiotensin II; Insulin
• ISSN: 0165-0327; 1573-2517
• DOI: 10.1016/j.jad.2024.01.228

Metformin (MET) is a drug used in the treatment of type 2 diabetes due to its insulin receptor sensitizing properties and anti-hepatic gluconeogenesis effect. One of the comorbidities in diabetes is the depression. This review aimed at summarizing the results of the available MET, depression and diabetes studies to clarify the possible role of MET in the depression during diabetes. A bibliographic search on PubMed, Embase, PsycINFO, Web of Science, Cochrane Central for studies referring to MET, depression and diabetes. Several studies have associated depression to the chronic inflammation that characterizes diabetes. Additionally MET is an anti-inflammatory molecule that generally acts by activating AMPK and inhibiting the NF-kB factor. In the context of diabetes, MET can act directly as an anti-inflammatory drug as well as inhibiting other pro-inflammatory molecules. In this regard, MET may inhibit the pro-inflammatory effects of angiotensin II. By facilitating the action of insulin and reducing hepatic gluconeogenesis, MET reduces circulating glucose levels, decreasing the formation of advanced glycation end products and therefore inflammation. During diabetes, the gut microbiota and the permeability of the intestinal barrier are altered, causing high levels of circulating lipopolysaccharides (LPS), which induce inflammation. MET can normalize the microbiota and the intestinal barrier permeability reducing the levels of LPS and inflammation. Clinical and experimental studies show the anti-depressant effect of MET mediated by different mechanisms both at the peripheral level and in the central nervous system. Therefore, MET as an anti-inflammatory drug can decrease symptoms of depression and represents a therapeutic approach to improve the psychological state of patients with diabetes. Additionally, insulin also has an anti-inflammatory effect that could act together with MET. Metformin (MET) is capable of decreasing inflammation and depression mediated by insulin receptor sensitization, decreased serum glucose levels, inhibition of neoglucogenesis, inhibition of angiotensin II (Ang II), normalization of gut microbiota and intestinal permeabilization and inhibition of NF-kB factor. [Display omitted] •Metformin (MET) is a drug with anti-inflammatory properties used in diabetes and metabolic syndrome.•Diabetes curses with manifestations of clinical depression.•Depression has been related to inflammatory processes.•MET with its anti-inflammatory property and inhibition of other pro-inflammatory molecules can improve depression in diabetes.