ASK DIS: 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

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