Metformin May Substantially Lower the Risk of Dementia

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This article was originally written and posted on March 26, 2026, and was updated on September 1, 2026

Could Metformin Lower the Risk of Dementia?

A preprint study released in August 2026, from the Diabetes Prevention Program Outcomes Study reported that long-term treatment with the diabetes medication Metformin, the most commonly prescribed type 2 diabetes medication, may substantially lower the risk of dementia over the following decades [1].

Until recently, Metformin’s mechanism of action was largely unknown, but a July 2025 study suggested that Metformin worked directly in the brain [2], even though it was previously accepted that this medication primarily reduces glucose produced by the liver by altering gut function [3]. 

Why Is Metformin Prescribed?

Metformin is often prescribed for conditions driven by insulin resistance, including type 2 diabetes and Polycystic Ovarian Syndrome (PCOS), and I have also encountered individuals taking Metformin to reduce their risk factors for Alzheimer’s disease, which has been referred to as “type 3 diabetes”. This recent pre-publication study provides intriguing evidence that may support Metformin use to reduce dementia risk.

How was the Metformin-Dementia Study Conducted?

The Metformin-dementia study was conducted through the Diabetes Prevention Program that began in the late 1990s and followed people at high risk for type 2 diabetes for more than 20 years, and examined cognitive outcomes decades later.

What Did the Metformin-Dementia Study Find?

Of the 1,483 participants assessed from 2022–2024, long-term follow-up found that only 1.9% of those randomized to receive Metformin for an average of 15.5 years eventually developed dementia, compared to 3.5% in the placebo group and 4.2% in the intensive lifestyle intervention group.

This translates to a ~60% lower odds of dementia in the Metformin group compared to those taking a placebo, and a ~62% lower odds of dementia in the Metformin group compared to an intensive lifestyle program

What Were the Limitations of the Metformin-Dementia Study?

The number of dementia cases reported in this study was relatively small, and the overall distribution of cognitive impairment did not significantly differ between the treatment groups. As a result, these findings are unable to prove that Metformin prevents dementia, but after more than two decades of follow-up, the results provide intriguing evidence that this low-cost medication may have benefits in lowering the risk of dementia.

How Does Metformin Affect the Body?

Traditional medical science has long established that Metformin works by lowering liver glucose production and changing gut activity. New evidence demonstrates that the brain is also a major driver in how this medication lowers daily blood sugar levels across different populations.

It has been known since 1967 that Metformin acts by reducing glucose produced in the liver [3], and since 1994 that this diabetes medication alters gut function [4], but a study published at the end of June 2025 shows that Metformin works directly in the brain [2].

Scientists have known since 2013 that the brain was a key regulator of blood sugar (glucose) [5],[6], but how the brain contributed to the blood glucose-lowering effect of Metformin was unknown.

How Does Metformin Affect Hunger?

Metformin travels to a specific area of the brain called the ventromedial hypothalamus to switch off a protein called Rap1. This vital interaction helps reset the brain pathway that controls appetite and signals that the body is no longer hungry.

A preliminary animal study in 2021 identified a brain protein called Repressor/Activator Protein 1 (Rap1) that impacts blood sugar metabolism in the ventromedial hypothalamus (VMH) [7], a part of the brain that has long been thought of as the “satiety center“[8] that signals that a person is no longer hungry.

A new animal study, published on July 30, 2025, reported that Metformin reaches the ventromedial hypothalamus, where it turns off Rap1 [2]. At clinically relevant doses, Metformin’s ability to lower blood sugar depends entirely on this brain pathway, and without this interaction in the hypothalamus, the medication’s glucose-lowering effects are significantly less.

Could Metformin Help With Alzheimer’s?

The scientific literature has demonstrated that Metformin crosses the blood-brain barrier in clinically relevant amounts in both animals [9] and humans [10]. This has important implications for Alzheimer’s disease, where Metformin has already been reported to improve executive functioning and is suggested to improve learning, memory, and attention [10].

This new study from the Diabetes Prevention Program Outcomes Study found that long-term use of Metformin may substantially lower the risk of dementia over the following decades [1]. 

More Info

Learn about me, and for those who want to lower the high blood sugar of type 2 diabetes or pre-diabetes, have a look at the Comprehensive Dietary Package, and for women with PCOS, learn more about the Polycystic Ovarian Syndrome Package.

To your good health!

Joy

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Quick Clinical Summary

Q: Could Metformin Lower the Risk of Dementia?

A: A recent preprint study published in August 2026 found that long-term treatment with Metformin resulted in ~60% lower odds of dementia compared to placebo, and ~62% lower odds of dementia compared to an intensive lifestyle program.

Q: Does Metformin Prevent Dementia?

A: No, the number of dementia cases reported in this study was relatively small, and the overall distribution of cognitive impairment did not significantly differ between the treatment groups, so the study did not prove that Metformin prevents dementia.

Q: Can Metformin help with Alzheimer’s disease functioning?

A: Scientific literature suggests Metformin crosses the blood-brain barrier in clinically relevant amounts and can improve executive functioning, learning, memory, and attention in individuals with Alzheimer’s disease.

 

References

  1. Wander PL, Doherty L, Pan Q, et al, DPP Research Group. Randomized metformin and cognitive outcomes in the Diabetes Prevention Program Outcomes Study. medRxiv [Preprint]. 2026 Aug 7:2026.08.05.26359234. doi: 10.64898/2026.08.05.26359234. PMID: 42620159; PMCID: PMC13484821.
  2. Hsiao-Yun Lin et al. Low-dose metformin requires brain Rap1 for its antidiabetic action, July 30, 2025, Sci. Adv.11,eadu3700(2025).DOI:10.1126/sciadv.adu3700
  3. F. Meyer, M. Ipaktchi, H. Clauser, Specific inhibition of gluconeogenesis by biguanides. Nature 213, 203–204 (1967).
  4. C. J. Bailey, K. J. Mynett, T. Page, Importance of the intestine as a site of metformin-stimulated glucose utilization. Br. J. Pharmacol. 112, 671–675 (1994).
  5. B. E. Grayson, R. J. Seeley, D. A. Sandoval, Wired on sugar: The role of the CNS in the regulation of glucose homeostasis. Nat. Rev. Neurosci. 14, 24–37 (2013).
  6. M. W. Schwartz, R. J. Seeley, M. H. Tschop, S. C. Woods, G. J. Morton, M. G. Myers, D. D’Alessio, Cooperation between brain and islet in glucose homeostasis and diabetes. Nature 503, 59–66 (2013).
  7. K. Kaneko, H. Y. Lin, Y. Fu, P. K. Saha, A. B. De la Puente-Gomez, Y. Xu, K. Ohinata, P. Chen, A. Morozov, M. Fukuda, Rap1 in the VMH regulates glucose homeostasis. JCI Insight 6, e142545 (2021).
  8. King BM. The rise, fall, and resurrection of the ventromedial hypothalamus in the regulation of feeding behavior and body weight. Physiol Behav. 2006 Feb 28;87(2):221-44. doi: 10.1016/j.physbeh.2005.10.007. Epub 2006 Jan 18. PMID: 16412483.
  9. A. Thinnes, M. Westenberger, C. Piechotta, A. Lehto, F. Wirth, H. Lau, J. Klein, Cholinergic and metabolic effects of metformin in mouse brain. Brain Res. Bull. 170, 211–217 (2021).
  10. A. M. Koenig, D. Mechanic-Hamilton, S. X. Xie, M. F. Combs, A. R. Cappola, L. Xie, J. A. Detre, D. A. Wolk, S. E. Arnold, 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 (2017).
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