Metformin

  • Commonly prescribed as a drug for Type 2 Diabetes
  • First approved for use in the United States in 1995
  • Commonly used for PCOS
  • May have other important effects
    •      Antitumor
    •      Antiaging
    •      Cardioprotective
    •      Neuroprotective
  • Adverse effects
    • Gastro intestinal
    • Lactic acidosis

Anticancer Effects

  • 500mg per day
  • May reduce incidence of colorectal, liver, and pancreas cancers
  • May reduce mortality from cancer
  • May have benefit as an adjuvant agent in cancer treatment
  • Antitumor effect may also carry over to other cancers such as breast, ovarian, and prostate cancers
  • Some studies do not support the above conclusions
  • Effect may occur through the direct actions on the cell, alterations in insulin and IgF1, alteration of the AMPK pathway, altered lipognesis, angiogenesis, anti-inflammation, alteration of TILs
  • Further prospective trials are needed to further elucidate these effects

Antiaging Effects

  • Effects have been demonstrated in nematodes and mice
  • May mimic intermittent or prolonged fasting, mild caloric restriction combined with a low glycemic index diet and protein restriction which have been suggested to help with health span and life span
  • May act through inhibition of the GH/IGF-I axis, inhibition of TOR–S6K signaling, activation of sirtuins, and AMPK pathway alteration
  • Metformin decreases insulin and IGF-1 levels, reduces the endogenous production of reactive oxygen species, alters AMPK and mTOR signaling
  • Influences metabolic and cellular processes such as inflammation
  • Clnical trials are required in order to determine metformin’s effect on healthspan in helathy individuals

Cardioprotective Effects

  • A number of clinical studies have shown that metformin has cardiovascular protective effects  and these effects are independent of glucose-lowering effects.
  • Metformin may improve lipometabolism and reduce the level of LDL cholesterol
  • Metformin is associated with weight loss or less weight gain
  • Metformin could effectively lower systolic blood pressure
  • Metformin can alleviate oxidative stress and inflammatory response as well as improve endothelial cell function

Neuroprotective Effects

  • Studies have been inconsistent
  • Alteration of AMPK pathway may be neuroprotective, via the enhancement of angiogenesis, neurogenesis and induction of autophagy
  • Metformin can also prevent brain mitochondrial dysfunction, decrease oxidative stress, increase brain-derived neurotrophic factor levels, ameliorate cognitive impairment and improve neurological deficits
  • Additional studies are neded