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Thursday, August 20, 2015

Metformin & Hyperpigmentation

Does it CAUSE Hyperpigmentation?

  • Generally does not have any adverse reactions related to skin
  • Very rare (1 in 10,000) may experience skin reactions such as rash, itching or flushing
  • Some case reports:
  • Leukocytoclastic vasculitis and psoriasiform drug eruption are the two most common presentations of metformin allergy
  • lichenoid reaction of the oral mucosa may also occur
  • Grinspan's syndrome (the triad of oral lichen planus, diabetes mellitus, and hypertension) could be seen in metformin allergy

Metformin & Vitamin B12 Deficiency

  • Chronic metformin use results in vitamin B12 deficiency in 30% of patients.
  •  Exhaustion of vitamin B12 stores usually occurs after twelve to fifteen years of absolute vitamin B12 deficiency. 
  • may present without anemia and as a peripheral neuropathy, is often misdiagnosed as diabetic neuropathy, although the clinical findings are usually different.
  • A retrospective and prospective study of 63 individuals with vitamin B12 deficiency-related neurological syndromes in India showed that 41 % had skin and mucosal changes, hyperpigmentation in 19 % subjects
  • mechanism of hyperpigmentation due to vitamin B12 deficiency is an increase in melanin synthesis

Application as TREATMENT for Hyperpigmentation?

  • Lehraiki et al. report that metformin, an antidiabetic drug, inhibited melanogenesis, in vitro and in vivo, and they suggest that metformin may be used to treat hyperpigmentation disorders.
  • topical application of metformin induced tail whitening in mice
  • metformin led to reduced melanin content in melanoma cells and in normal human melanocytes by decreasing cAMP accumulation and cAMP-responsive element-binding protein phosphorylation
  • showed antimelanogenic effect of metformin on reconstituted human epidermis and on human skin biopsies


  1. References:
  2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3081469/
  3. http://www.ehealthme.com/ds/metformin/skin+hyperpigmentation
  4. http://www.uv.es/bagan/Docencia/ampliacion/reaccionesfarmacos.pdf
  5. http://www.medscape.com/viewarticle/719043_2

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