Metformin, diabetes drug, and dementia

Metformin

  • Drugs
  • Updated April 2, 2018

Metformin is a prescription drug used to treat type 2 diabetes. In diabetics, it can help to control blood sugar and insulin sensitivity. Type 2 diabetes is a risk factor for Alzheimer's disease, and insulin sensitivity may be altered in Alzheimer's patients. Some studies suggest metformin may reduce Alzheimer's risk, but others have found long-term use may increase it. No large clinical trials have confirmed whether metformin is beneficial in non-diabetic Alzheimer’s patients. And long-term metformin use may decrease blood levels of vitamin B12, so levels should be monitored by a physician.

Evidence

Our search identified:

  • 1 meta-analysis for Alzheimer's prevention
  • 2 small clinical studies in patients with mild cognitive impairment or mild Alzheimer's disease
  • 6 observational studies for future Alzheimer's risk in patients with type-2 diabetes
  • Numerous preclinical studies

Potential Benefit

Multiple observational studies have reported varying results on whether metformin may be beneficial for preventing Alzheimer's disease in type 2 diabetes patients. Three studies reported a decreased risk for cognitive impairment or dementia in diabetic patients taking metformin compared to those not taking medication or taking other diabetes drugs [1][2][3]. Additionally, one meta-analysis suggested a trend for reduced risk of dementia with metformin use in diabetics [4]. Three other studies, however, reported an increased risk for impaired cognitive performance, dementia, or Alzheimer's disease with metformin use compared to those taking other medications [5][6][7]. One study reported that longer metformin use was associated with an increasing risk for dementia [6].

Several factors could account for the varying results. Many of these studies do not account for diabetes duration, severity, or how well diabetes is controlled [8]. Also, metformin is often used to treat mild diabetes, so patients taking other drugs may have more severe diabetes. Additionally, long-term metformin use can decrease vitamin B12 levels, which may be a potential risk factor for Alzheimer's disease. One study reported that when controlling for vitamin B12 levels, metformin was no longer significantly associated with increased risk of Alzheimer's [7][9].

It is currently unknown whether metformin would prevent Alzheimer's disease in non-diabetic patients. Whether with metformin or another method, controlling diabetes is important for reducing your risk for Alzheimer's disease. If you are taking metformin, you should speak to your doctor about monitoring your vitamin B12 levels.

APOE4 Carriers:

One observational study reported a reduced risk for Alzheimer's disease after controlling for APOE4 status, though it is unknown if it is better for APOE4 carriers or not [1]. For more information on what the APOE4 gene allele means for your health, read our APOE4 information page.

For Dementia Patients

In two clinical studies in non-diabetic patients with mild cognitive impairment or mild Alzheimer's disease, metformin improved some aspects of cognition, but not others. There were no changes in other Alzheimer's biomarkers [10][11]. However, both studies were likely too small and short to show a clinical benefit.

Safety

The most common side effect metformin users experience is gastrointestinal discomfort—which can lead to weight loss—but this discomfort may decrease over time [12]. Some evidence suggests that metformin may decrease levels of vitamin B12 thus increasing the risk of diabetic neuropathy [13]. Additionally, some reports suggest that metformin may increase the risk of lactic acidosis, a buildup of lactate which can decrease the blood's pH [14]. Metformin has, however, been available for many years and has a good safety profile. It does have many drug interactions that should be discussed with your doctor before use.

NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.

How to Use

Metformin (sold as Glucophage or Glucophage XR – extended release) is available by prescription. For diabetes patients, it is usually started at 500mg twice per day and increased up to 2g/day in divided doses.

Learn More

More information on side effects and drug interactions is available on Drugs.com.

Learn more about the Targeting Aging with Metformin (TAME) trial, which is the first aging clinical study.

References

  1. Ng TP, Feng L, Yap KB et al. (2014) Long-term metformin usage and cognitive function among older adults with diabetes. J Alzheimers Dis 41, 61-68.
  2. Cheng C, Lin CH, Tsai YW et al. (2014) Type 2 diabetes and antidiabetic medications in relation to dementia diagnosis. J Gerontol A Biol Sci Med Sci 69, 1299-1305.
  3. Hsu CC, Wahlqvist ML, Lee MS et al. (2011) Incidence of dementia is increased in type 2 diabetes and reduced by the use of sulfonylureas and metformin. J Alzheimers Dis 24, 485-493.
  4. Ye F, Luo YJ, Xiao J et al. (2016) Impact of Insulin Sensitizers on the Incidence of Dementia: A Meta-Analysis. Dement Geriatr Cogn Disord 41, 251-260.
  5. Imfeld P, Bodmer M, Jick SS et al. (2012) Metformin, other antidiabetic drugs, and risk of Alzheimer's disease: a population-based case-control study. J Am Geriatr Soc 60, 916-921.
  6. Kuan YC, Huang KW, Lin CL et al. (2017) Effects of metformin exposure on neurodegenerative diseases in elderly patients with type 2 diabetes mellitus. Prog Neuropsychopharmacol Biol Psychiatry 79, 77-83.
  7. Moore EM, Mander AG, Ames D et al. (2013) Increased risk of cognitive impairment in patients with diabetes is associated with metformin. Diabetes Care 36, 2981-2987.
  8. Goodarzi MO (2014) Comment on Moore et al. Increased risk of cognitive impairment in patients with diabetes is associated with metformin. Diabetes care 2013; 36:2981-2987. Diabetes Care 37, e150.
  9. Moore EM, Mander AG, Ames D et al. (2014) Response to comment on Moore et al. Increased risk of cognitive impairment in patients with diabetes is associated with metformin. Diabetes care 2013; 36:2981-2987. Diabetes Care 37, e151.
  10. Koenig AM, Mechanic-Hamilton D, Xie SX et al. (2017) Effects of the Insulin Sensitizer Metformin in Alzheimer Disease: Pilot Data From a Randomized Placebo-controlled Crossover Study. Alzheimer Dis Assoc Disord 31, 107-113.
  11. Luchsinger JA, Perez T, Chang H et al. (2016) Metformin in Amnestic Mild Cognitive Impairment: Results of a Pilot Randomized Placebo Controlled Clinical Trial. J Alzheimers Dis 51, 501-514.
  12. Diabetes Prevention Program Research G (2012) Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. Diabetes Care 35, 731-737.
  13. Aroda VR, Edelstein SL, Goldberg RB et al. (2016) Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab 101, 1754-1761.
  14. Huang W, Castelino RL, Peterson GM (2017) Lactate Levels with Chronic Metformin Use: A Narrative Review. Clin Drug Investig 37, 991-1007.