Latest research on Metformin

Metformin is a biguanide antihyperglycemic agent used for treating non-insulin-dependent diabetes mellitus (NIDDM). It improves glycemic control by decreasing hepatic glucose production, decreasing glucose absorption and increasing insulin-mediated glucose uptake. Metformin is the only oral antihyperglycemic agent that is not associated with weight gain. Metformin may induce weight loss and is the drug of choice for obese NIDDM patients. When used alone, metformin does not cause hypoglycemia; however, it may potentiate the hypoglycemic effects of sulfonylureas and insulin. Its main side effects are dyspepsia, nausea and diarrhea. Dose titration and/or use of smaller divided doses may decrease side effects. Metformin should be avoided in those with severely compromised renal function (creatinine clearance < 30 ml/min), acute/decompensated heart failure, severe liver disease and for 48 hours after the use of iodinated contrast dyes due to the risk of lactic acidosis. Lower doses should be used in the elderly and those with decreased renal function. Metformin decreases fasting plasma glucose, postprandial blood glucose and glycosolated hemoglobin (HbA1c) levels, which are reflective of the last 8-10 weeks of glucose control. Metformin may also have a positive effect on lipid levels. In 2012, a combination tablet of linagliptin plus metformin hydrochloride was marketed under the name Jentadueto for use in patients when treatment with both linagliptin and metformin is appropriate.

Latest findings

Metformin is a first-line drug for treating type 2 diabetes; its proposed mechanism of action involves the AMPK activation [32]. [source, 2016]
To evaluate whether similar effects occur in C. elegans, we exposed wild-type N2 nematodes to a high glucose concentration (100 mM) in the presence or absence of Metformin (50 mM, 24 h). [source, 2016]
We observed that basal AAK phosphorylation decreased upon glucose administration with respect to control animals, whereas treatment with both glucose and Metformin significantly increased AAK phosphorylation even more than control nematodes (Fig 7A). [source, 2016]
Altogether, our results suggest that Metformin could reverse the effects generated by high glucose availability in an AAK-dependent manner, since such changes were not observed in the aak-2 mutant strain exposed to high glucose or high glucose plus Metformin (Fig 7D and 7E). [source, 2016]
To test this idea, we first activated AAK by AICAR or Metformin exposure. [source, 2016]
The concentrations of AICAR and Metformin used in our experiments were sufficient to increase AAK activation over the time course evaluated, being faster and more pronounced by AICAR. [source, 2016]
This fact may reflect a positive allosteric effect of the ZMP, the phosphorylated form of AICAR, similar to AMP, in the worm kinase, which takes place with maximal phosphorylation at 12 h; whereas with Metformin this effect was reached until 24 hours of exposure, consistent with the accepted consensus that Metformin indirectly activates AMPK [32]. [source, 2016]
Nevertheless, we cannot exclude the possibility that AICAR has a different potential to activate AAK in comparison with Metformin, which would need further experimental exploration. [source, 2016]
Augmented Oxygen consumption by Metformin treatment a priori seems inconsistent with the general idea that Metformin inhibits complex I of the mitochondrial electron transport chain and hence decreases respiration [40]. [source, 2016]
Indeed, Metformin inhibition of complex I is an acute process, whereas the observed result in the worm seems a long term effect. [source, 2016]