Diabetes Therapies for Dementia
Purpose of review
Type 2 diabetes (T2D) is a well-established risk factor for the development of dementia. Dementia and T2D share some underlying pathophysiology that has led to interest in the potential to repurpose drugs used in the management of T2D to benefit brain health. This review describes the scientific data available on the use of T2D medications for the risk reduction or management of dementia, in people with and without T2D.
Results from basic laboratory research support the potential for commonly-used medications for T2D, including those with direct glucose-lowering properties, to have a beneficial effect on brain health. However, human studies have been mostly observational in nature and report conflicting results. Preliminary data suggest that intranasal insulin, metformin, and GLP-1 agonists show promise for dementia, but confirmatory evidence for their benefit in dementia is still lacking.
Current evidence does not support the repurposing of T2D medications for dementia risk reduction or management. Research in the field of T2D and dementia is active, and further data are required before definitive conclusions can be drawn.
KeywordsType 2 diabetes Dementia Drugs
Compliance with Ethical Standards
Conflict of Interest
Chris Moran, Michele L. Callisaya, and Velandai Srikanth each declares no potential conflicts of interest. Zoe Arvanitakis reports grants from National Institutes of Health (R01 NS084965 and RF1 AG059621), during the conduct of the study; other from Amylyx, outside the submitted work.
Human and Animal Rights and Informed Consent
This article is a review of the published scientific literature, and no human or animal subjects were studied by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance
- 2.Walker VM, Davies NM, Jones T, Kehoe PG, Martin RM. Can commonly prescribed drugs be repurposed for the prevention or treatment of Alzheimer's and other neurodegenerative diseases? Protocol for an observational cohort study in the UK clinical practice research datalink. BMJ Open. 2016;6(12):e012044.PubMedPubMedCentralGoogle Scholar
- 8.Moran C, Beare R, Wang W, Callisaya M, Srikanth V, Alzheimer's disease neuroimaging I. Type 2 diabetes mellitus, brain atrophy, and cognitive decline. Neurology. 2019.Google Scholar
- 10.• Vieira MNN, Lima-Filho RAS, De Felice FG. Connecting Alzheimer's disease to diabetes: underlying mechanisms and potential therapeutic targets. Neuropharmacology. 2018;136(Pt B):160–71 An excellent review article expanding upon the potential mechanistic pathways that may be relevant in the repurposing of drugs used in the management of T2D for the prevention or management of dementia.PubMedGoogle Scholar
- 13.• Weinstein G, Davis-Plourde KL, Conner S, Himali JJ, Beiser AS, Lee A, et al. Association of metformin, sulfonylurea and insulin use with brain structure and function and risk of dementia and Alzheimer's disease: pooled analysis from 5 cohorts. PLoS One. 2019;14(2):e0212293 A recent and large study combining 5 separate cohort studies that sheds important light on the associations between commonly-used glucose-lowering drugs in T2D and dementia risk. PubMedPubMedCentralGoogle Scholar
- 15.American Diabetes A. Standards of Medical Care in Diabetes 2018. Diabetes care. 2018;40(S1).Google Scholar
- 47.Biessels GJ, Janssen J, van den Berg E, Zinman B, Espeland MA, Mattheus M, et al. Rationale and design of the CAROLINA(R) - cognition substudy: a randomised controlled trial on cognitive outcomes of linagliptin versus glimepiride in patients with type 2 diabetes mellitus. BMC Neurol. 2018;18(1):7.PubMedPubMedCentralGoogle Scholar
- 48.Rosenstock J, Perkovic V, Alexander JH, Cooper ME, Marx N, Pencina MJ, et al. Rationale, design, and baseline characteristics of the CArdiovascular safety and Renal Microvascular outcomE study with LINAgliptin (CARMELINA((R))): a randomized, double-blind, placebo-controlled clinical trial in patients with type 2 diabetes and high cardio-renal risk. Cardiovasc Diabetol. 2018;17(1):39.PubMedPubMedCentralGoogle Scholar
- 49.Cukierman-Yaffe T, Bosch J, Diaz R, Dyal L, Hancu N, Hildebrandt P, et al. Effects of basal insulin glargine and omega-3 fatty acid on cognitive decline and probable cognitive impairment in people with dysglycaemia: a substudy of the ORIGIN trial. Lancet Diabetes Endocrinol. 2014;2(7):562–72.PubMedGoogle Scholar