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Metformin Hair and Skin Changes: What the Evidence Actually Shows

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At a glance

  • Labeled use / type 2 diabetes; PCOS is off-label [1]
  • B12 in 29-week trials / subnormal in about 7% [1]
  • B12 monitoring / hematologic parameters yearly; vitamin B12 every 2 to 3 years [1]
  • DPPOS at 5 years / low B12 4.3% with metformin vs 2.3% with placebo [2]
  • Reactions reported in 1% to 5% / includes rash and nail disorder [1]
  • PCOS review / 44 trials, 3,992 women; main outcomes were reproductive [3]
  • Acanthosis nigricans / one review lists metformin among common treatments, no response rate [4]

Does metformin cause hair loss?

Hair loss is not listed as an adverse reaction in the immediate-release metformin tablet label [1]. Whether metformin causes hair loss therefore remains unclear. What the label does describe is a vitamin B12 effect: in 29-week trials, previously normal B12 levels fell to subnormal in about 7% of patients [1]. The label says this may be associated with anemia but appears to be rapidly reversible with discontinuation of metformin or vitamin B12 supplementation [1]. The label says to measure hematologic parameters annually and vitamin B12 at 2 to 3 year intervals, and to manage any abnormalities [1].

Longer-term data show the same B12 signal. In the Diabetes Prevention Program Outcomes Study, low B12 (203 pg/mL or less) was 4.3% with metformin vs 2.3% with placebo at 5 years [2]. Combined low and borderline-low B12 (298 pg/mL or less) was 19.1% vs 9.5% [2]. Each year of metformin use was associated with a 13% higher odds of B12 deficiency (OR 1.13, 95% CI 1.06 to 1.20) [2].

What about skin changes?

The label's adverse-reactions list is where skin findings appear. Rash and nail disorder were reported in 1% to 5% of metformin-treated patients and more often than with placebo [1]. They sit in the same list as abnormal stools, hypoglycemia, myalgia, lightheadedness, dyspnea, increased sweating, taste disorder and flushing [1]. Acne and pigmentation changes are not in the label's adverse-reaction lists [1].

Metformin is not labeled for PCOS; the labeled indication is type 2 diabetes [1]. A Cochrane review of insulin-sensitising drugs in PCOS (44 trials, 3,992 women, 38 of them metformin trials) reports reproductive outcomes such as pregnancy and live birth [3]. These trials do not establish whether metformin helps acne in PCOS [3].

One review of acanthosis nigricans, a condition of dark, thickened, velvety skin, lists metformin among the most common treatment modalities, along with retinoids, without giving a metformin response rate [4].

Frequently asked questions

Does metformin cause hair loss?
Hair loss is not listed as an adverse reaction in the immediate-release metformin tablet label [1]. Whether metformin causes hair loss remains unclear. The label does warn that metformin can lower vitamin B12, with subnormal levels in about 7% of patients in 29-week trials [1].
Can metformin help acne in PCOS?
Metformin is not labeled for PCOS; its labeled indication is type 2 diabetes [1]. The Cochrane PCOS review reports reproductive outcomes, not whether metformin improves acne [3].
Does metformin change skin pigmentation?
Pigmentation changes are not listed in the label's adverse reactions [1]. A review of acanthosis nigricans lists metformin among the most common treatment modalities, along with retinoids, without giving a response rate [4]. The label reports rash and nail disorder in 1% to 5% of metformin-treated patients, more often than with placebo [1].

References

  1. U.S. National Library of Medicine, DailyMed. Metformin hydrochloride tablets (Granules, immediate-release) prescribing information. Metformin hydrochloride tablets (Granules, immediate-release) label
  2. Aroda VR, Edelstein SL, Goldberg RB, Knowler WC, Marcovina SM, Orchard TJ, et al. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016;101(4):1754-61. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study
  3. Tang T, Lord JM, Norman RJ, Yasmin E, Balen AH. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev. 2012(5):CD003053. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility
  4. Phiske MM. An approach to acanthosis nigricans. Indian Dermatol Online J. 2014;5(3):239-49. An approach to acanthosis nigricans
Evidence overview for metformin: Metformin Hair and Skin Changes: What the Evidence Actually Shows