60 years of metformin use: a glance at the past and a look to the future

Marshall, Sally M.

doi:10.1007/s00125-017-4343-y

Cited by 114 publications

(81 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Metformin has been established as the first‐line oral glucose‐lowering agent in most, if not all, international clinical guidelines on the management of type 2 diabetes (T2DM) . Surprisingly, the mechanism(s) underlying its anti‐diabetic action remain incompletely understood, and an improved understanding would potentially help optimize its glucose‐lowering efficacy.…”

Section: Introductionmentioning

confidence: 99%

Comparative effects of proximal and distal small intestinal administration of metformin on plasma glucose and glucagon‐like peptide‐1, and gastric emptying after oral glucose, in type 2 diabetes

Borg

Bound

Grivell

et al. 2018

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

Aims The gastrointestinal tract, particularly the lower gut, may be key to the anti‐diabetic action of metformin. We evaluated whether administration of metformin into the distal, vs the proximal, small intestine would be more effective in lowering plasma glucose by stimulating glucagon‐like pepetide‐1 (GLP‐1) and/or slowing gastric emptying (GE) in type 2 diabetes (T2DM). Materials and methods Ten diet‐controlled T2DM patients were studied on three occasions. A transnasal catheter was positioned with proximal and distal infusion ports located 13 and 190 cm beyond the pylorus, respectively. Participants received infusions of (a) proximal + distal saline (control), (b) proximal metformin (1000 mg) + distal saline or (c) proximal saline + distal metformin (1000 mg) over 5 minutes, followed 60 minutes later by a glucose drink containing 50 g glucose and 150 mg 13C‐acetate. “Arterialized” venous blood and breath samples were collected over 3 hours for measurements of plasma glucose, GLP‐1, insulin and glucagon, and GE, respectively. Results Compared with control, both proximal and distal metformin reduced plasma glucose and augmented GLP‐1 responses to oral glucose comparably (P < 0.05 each), without affecting plasma insulin or glucagon. GE was slower after proximal metformin than after control (P < 0.05) and tended to be slower after distal metformin, without any difference between proximal and distal metformin. Conclusions In diet‐controlled T2DM patients, glucose‐lowering via a single dose of metformin administered to the upper and lower gut was comparable and was associated with stimulation of GLP‐1 and slowing of GE. These observations suggest that the site of gastrointestinal administration is not critical to the glucose‐lowering capacity of metformin.

show abstract

Section: Introductionmentioning

confidence: 99%

Comparative effects of proximal and distal small intestinal administration of metformin on plasma glucose and glucagon‐like peptide‐1, and gastric emptying after oral glucose, in type 2 diabetes

Borg

Bound

Grivell

et al. 2018

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

show abstract

“…However, predominantly in elderly individuals, with heart failure, hypoxia, sepsis, renal and hepatic comorbidities, and dehydration, metformin administration can lead to lactic acidosis in rare cases [15][16][17][18]. The confirmed anti-hyperglycemic effect (without causing hypoglycemia) and the favorable safety prolife when compared to phenformin and buformin helped metformin claim the title as the 'most widely prescribed and first-line oral anti-diabetic drug' and manages to keep that title 62 years after its first clinical use in the treatment and management of type 2 diabetes [13,14,19].Metformin decreases the levels of blood glucose by decreasing gluconeogenesis and glycogenolysis in the liver, decreasing the intestinal absorption of glucose, reducing the release of free fatty acids (FFA) from adipose tissue, and increasing glucose utilization by the muscle (Figure 1) [20]. Apart from its glucose-lowering effect, metformin was studied for its cardioprotective and vasculo-protective effects and more recently for its effects as a cancer preventive and anti-cancer/anti-tumor agent in different cancers (Figure 1) [5,20,21].…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Metformin: The Answer to Cancer in a Flower? Current Knowledge and Future Prospects of Metformin as an Anti-Cancer Agent in Breast Cancer

et al. 2019

View full text Add to dashboard Cite

Interest has grown in studying the possible use of well-known anti-diabetic drugs as anti-cancer agents individually or in combination with, frequently used, chemotherapeutic agents and/or radiation, owing to the fact that diabetes heightens the risk, incidence, and rapid progression of cancers, including breast cancer, in an individual. In this regard, metformin (1, 1-dimethylbiguanide), well known as ‘Glucophage’ among diabetics, was reported to be cancer preventive while also being a potent anti-proliferative and anti-cancer agent. While meta-analysis studies reported a lower risk and incidence of breast cancer among diabetic individuals on a metformin treatment regimen, several in vitro, pre-clinical, and clinical studies reported the efficacy of using metformin individually as an anti-cancer/anti-tumor agent or in combination with chemotherapeutic drugs or radiation in the treatment of different forms of breast cancer. However, unanswered questions remain with regards to areas such as cancer treatment specific therapeutic dosing of metformin, specificity to cancer cells at high concentrations, resistance to metformin therapy, efficacy of combinatory therapeutic approaches, post-therapeutic relapse of the disease, and efficacy in cancer prevention in non-diabetic individuals. In the current article, we discuss the biology of metformin and its molecular mechanism of action, the existing cellular, pre-clinical, and clinical studies that have tested the anti-tumor potential of metformin as a potential anti-cancer/anti-tumor agent in breast cancer therapy, and outline the future prospects and directions for a better understanding and re-purposing of metformin as an anti-cancer drug in the treatment of breast cancer.

show abstract

“…Previous studies suggest that elevated circulating BCAA levels have been correlated with severity of insulin resistance (19,20). Metformin has been known to improve the regulation of glucose tolerance (21)(22)(23).…”

Section: Metformin-induced Decreased Glucose Intolerance In Imsud Micementioning

confidence: 99%

Metformin extends the lifespan of iMSUD mice by rescuing physiologic dysfunction and modulating mechanisms of mTORC1 activation

Hsu

Davis

Liao

et al. 2020

Preprint

View full text Add to dashboard Cite

Abstract Background- Dysregulation of branched chain amino acid (BCAA) catabolism caused by mutations in the metabolizing enzyme-branched chain alpha-keto acid dehydrogenase (BCKDH) leads to the fatal newborn disorder Maple Syrup Urine Disease (MSUD) and is linked to chronic diseases such as type 2 diabetes. Results- Here we show that a MSUD mouse model with severely reduced BCKDH activity exhibits glucose intolerance, altered mTOR signaling, decreased levels of TCA cycle intermediates, reduced distribution of Type I skeletal muscle fibers and activated AMP-activated protein kinase (AMPK) signaling, all of which can be ameliorated by long term treatment with metformin, which enhances the survival of these mice. Treatment with metformin was correlated with increased serum-levels of growth/differentiation factor GDF15 (GFD15) and adiponectin. We also found that branched chain keto acid regulates leucine-mediated activation of mTORC1 by preventing the dissociation of sestrin2-gator complex in vitro. Conclusions- In summary, our study suggests metformin could be an effective therapeutic candidate for MSUD patients and maps the crosstalk between key pathways that maintain metabolic homeostasis in MSUD.

show abstract

60 years of metformin use: a glance at the past and a look to the future

Cited by 114 publications

References 31 publications

Comparative effects of proximal and distal small intestinal administration of metformin on plasma glucose and glucagon‐like peptide‐1, and gastric emptying after oral glucose, in type 2 diabetes

Comparative effects of proximal and distal small intestinal administration of metformin on plasma glucose and glucagon‐like peptide‐1, and gastric emptying after oral glucose, in type 2 diabetes

Metformin: The Answer to Cancer in a Flower? Current Knowledge and Future Prospects of Metformin as an Anti-Cancer Agent in Breast Cancer

Metformin extends the lifespan of iMSUD mice by rescuing physiologic dysfunction and modulating mechanisms of mTORC1 activation

Contact Info

Product

Resources

About