Metformin: Mechanisms in Human Obesity and Weight Loss

Abstract

Purpose of Review: Metformin has multiple benefits for health beyond its antihyperglycemic properties. The purpose of this manuscript is to review the mechanisms that underlie metformin's effects on obesity.Recent Findings: Metformin is first line therapy for type 2 diabetes. Large cohort studies have shown weight loss benefits associated with metformin therapy. Metabolic consequences were traditionally thought to underlie this effect, including reduction in hepatic gluconeogenesis and reduction in insulin production. Emerging evidence suggests that metformin-associated weight loss is due to modulation of hypothalamic appetite-regulatory centers, alteration in the gut microbiome, and reversal of consequences of aging. Metformin is also being explored in the management of obesity's sequelae such as hepatic steatosis, obstructive sleep apnea and osteoarthritis.Summary: Multiple mechanisms underlie the weight loss-inducing and health-promoting effects of metformin. Further exploration of these pathways may be important in identifying new pharmacologic targets for obesity and other aging-associated metabolic diseases.

Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease

“…Thus, the precise mechanisms by which metformin lower blood glucose are complex and still evolving. While some diabetes medications have adverse effects on body weight, patients taking metformin often lose a small amount of weight [reviewed in (557)]. Studies in T2DM suggest that metformin may reduce body fat stores and promote a more metabolically healthy fat distribution (558)(559)(560).…”

GDF-15 as a Weight Watcher for Diabetic and Non-Diabetic People Treated With Metformin

“…Although most studies have confirmed that metformin could decrease body weight in diabetic and non-diabetic subjects, the mechanism still remains unclear. Aside from the mechanisms summarized in two reviews (77,78), recent study findings indicate that GDF-15 plays an independent role in body weight change in people taking metformin.…”

Type 2 Diabetes Mellitus Associated with Obesity (Diabesity). The Central Role of Gut Microbiota and Its Translational Applications

“…Beyond these effects, some studies have endorsed its potential use in loss weight, mainly due to the impact of metformin on food intake centres and as a gut microbiota regulator [ 218 ]. More precisely, Sun et al observed that after 3 days of metformin treatment, a significant decrease in the Bacteroides fragilis population was reported, followed by an increase in Glycoursodeoxycholic acid (GUDCA) [ 219 ]. This was associated with the inhibition mediated by FXR.…”