Metformin induces significant reduction of body weight, total cholesterol and LDL levels in the elderly – A meta-analysis

Solymár, Margit; Ivić, Ivan; Pótó, László; Hegyi, Péter; Garami, András; Hartmann, Petra; Pétervári, Erika; Czopf, László; Alizadeh, Hussain; Gyöngyi, Zoltán; Patrícia, Silvia; Simon, Mária; Mátrai, Péter; Bérczi, Bálint; Balaskó, Márta

doi:10.1371/journal.pone.0207947

Cited by 72 publications

(57 citation statements)

References 40 publications

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“…Studies suggest that metformin treatment of obese adults with type 2 diabetes could lead to weight loss and improved glucose tolerance as well as fat reserves. Metformin mainly exerts its anti-hyperglycemic effect by reducing the excretion of hepatic glucose through inhibiting gluconeogenesis causing reduced weight and blood glucose in type 2 diabetic patients [31]. Metformin appears to be effective in blood glucose control, lipid status, and weight control and can be a good therapy in obese type 2 diabetic patients.…”

Section: Bwimentioning

confidence: 99%

Concurrent metformin and silibinin therapy in diabetes: assessments in zebrafish (Danio rerio) animal model

Mohammadi

Manouchehri

Changizi

et al. 2020

J Diabetes Metab Disord

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Objective In this study, zebrafish was used as a biological model to induce type 2 diabetes mellitus through glucose. Then, the effect of metformin and silibinin combination was examined on elevated blood glucose, intestinal tissues, liver enzymes, and TNF-α, IFN-γ, INL1β genes as inflammation marker genes. Methods The liver enzymes (AST, ALT, and ALP) derived from fish viscera homogenate supernatants were assayed in an auto-analyzer. The expression of target genes was quantified on RNA extracted from the tails by an in-house RT-PCR method, with fine intestine tissue staining performed by hematoxylin and eosin protocol (H&E). Result In the glucose-free treatments, metformin and silymarin decreased the levels of AST, ALT, and ALP enzymes in the blood. The combination of these two drugs had also a significant role in reducing glucose levels. The body weight increased significantly in the control group which was affected by glucose concentration, with the lowest body weight gain observed in the metformin group. The expression of INL-1β gene was significantly enhanced in the control group and the highest IFN-γ expression was observed in both control groups with glucose (G + CTRL) and without glucose (G-CTRL) (p < 0.05). The lowest level of TNF-α gene expression was observed in the control + glucose group (G + CTRL) (p < 0.05). Diabetic state causes weak absorption whereby the fish body demands to increase absorption level by enhancing the amount of acidic goblet cells thereby acidifying the environment in the gastric tracts. Conclusion Collectively, this study indicated that treatment with metformin and Silibinin could improve metabolic-mediated performances by reducing the expression of inflammatory genes and blood glucose, modulating liver enzymes, and ameliorating the intestinal inflammation in type 2 diabetic zebrafish model.

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Section: Bwimentioning

confidence: 99%

Concurrent metformin and silibinin therapy in diabetes: assessments in zebrafish (Danio rerio) animal model

Mohammadi

Manouchehri

Changizi

et al. 2020

J Diabetes Metab Disord

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“…In another study done in adult obese women without resistance to insulin, who were given 500 mg of MTF twice a day for three months, no differences were found in body weight, body fat, and blood pressure levels, neither did the glucose, insulin, and IGF-1 plasma levels decreased [48]. A recent meta-analysis [49] showed that MTF treatment in elderly humans moderately diminishes body weight, along with a significant decrease in serum cholesterol and LDL, which could suggest a reduction in the risk of major coronary events and of mortality in elderly diabetic populations.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Moderate Exercise Combined with Metformin Treatment Induces an Hormetic Response That Prevents Strength and Muscle Mass Loss in Old Female Wistar Rats

Hernández-Álvarez

Mena-Montes

Toledo-Pérez

et al. 2019

Oxidative Medicine and Cellular Longevity

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Sarcopenia is a syndrome characterized by a progressive and generalized skeletal muscle mass and strength loss, as well as a poor physical performance, which as strongly been associated with aging. Sedentary lifestyle in the elderly contributes to this condition; however, physical activity improves health, reducing morbidity and mortality. Recent studies have shown that metformin (MTF) can also prevent muscle damage promoting muscular performance. To date, there is great controversy if MTF treatment combined with exercise training improves or nullifies the benefits provided by physical activity. This study is aimed at evaluating the effect of long-term moderate exercise combined with MTF treatment on body composition, strength, redox state, and survival rate during the life of female Wistar rats. In this study, rats performed moderate exercise during 20 of their 24 months of life and were treated with MTF for one year or for 6 months, i.e., from 12 to 24 months old and 18 to 24 months old. The body composition (percentage of fat, bone, and lean mass) was determined using a dual-energy X-ray absorption scanner (DXA), and grip strength was determined using a dynamometer. Likewise, medial and tibial nerve somatosensory evoked potentials were evaluated and the redox state was measured by HPLC, calculating the GSH/GSSG ratio in the gastrocnemius muscle. Our results suggest- that the MTF administration, both in the sedentary and the exercise groups, might activate a mechanism that is directly related to the induction of the hormetic response through the redox state modulation. MTF treatment does not eliminate the beneficial effects of exercise throughout life, and although MTF does not increase muscle mass, it increases longevity.

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“…In addition to lowering blood glucose, metformin consistently induces weight loss in people with or without type 2 diabetes [16][17][18][19][20][21] . This effect on weight loss is not due to increases in energy expenditure 17,22 , but instead involves the suppression of appetite 18,23 .…”

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confidence: 99%

Metformin-induced increases in GDF15 are important for suppressing appetite and promoting weight loss

et al. 2019

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Metformin is the most commonly prescribed medication for type 2 diabetes, owing to its glucose-lowering effects, which are mediated through the suppression of hepatic glucose production (reviewed in refs. 1-3). However, in addition to its effects on the liver, metformin reduces appetite and in preclinical models exerts beneficial effects on ageing and a number of diverse diseases (for example, cognitive disorders, cancer, cardiovascular disease) through mechanisms that are not fully understood 1-3. Given the high concentration of metformin in the liver and its many beneficial effects beyond glycemic control, we reasoned that metformin may increase the secretion of a hepatocyte-derived endocrine factor that communicates with the central nervous system 4. Here we show, using unbiased transcriptomics of mouse hepatocytes and analysis of proteins in human serum, that metformin induces expression and secretion of growth differentiating factor 15 (GDF15). In primary mouse hepatocytes, metformin stimulates the secretion of GDF15 by increasing the expression of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP; also known as DDIT3). In wild-type mice fed a high-fat diet, oral administration of metformin increases serum GDF15 and reduces food intake, body mass, fasting insulin and glucose intolerance; these effects are eliminated in GDF15 null mice. An increase in serum GDF15 is also associated with weight loss in patients with type 2 diabetes who take metformin. Although further studies will be required to determine the tissue source(s) of GDF15 produced in response to metformin in vivo, our data indicate that the therapeutic benefits of metformin on appetite, body mass and serum insulin depend on GDF15. Metformin is one of the most widely used medications in the world. It is a strong base that exists in its protonated form at physiological pH and therefore does not pass through cellular membranes easily. In rodents, oral administration of metformin (250-300 mg kg-1 body weight) results in clinically relevant plasma concentrations of approximately 10-15 μM; however, concentrations in the

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Metformin induces significant reduction of body weight, total cholesterol and LDL levels in the elderly – A meta-analysis

Cited by 72 publications

References 40 publications

Concurrent metformin and silibinin therapy in diabetes: assessments in zebrafish (Danio rerio) animal model

Concurrent metformin and silibinin therapy in diabetes: assessments in zebrafish (Danio rerio) animal model

Long-Term Moderate Exercise Combined with Metformin Treatment Induces an Hormetic Response That Prevents Strength and Muscle Mass Loss in Old Female Wistar Rats

Metformin-induced increases in GDF15 are important for suppressing appetite and promoting weight loss

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