Insulin shot

Liraglutide

  • Drugs
  • Updated July 27, 2017

Liraglutide is a prescription drug used to treat type 2 diabetes, which is a risk factor for Alzheimer's disease. In Alzheimer's disease, brain cells are often insulin resistant. And preclinical and preliminary clinical evidence suggest that liraglutide may benefit patients by controlling type 2 diabetes and reducing the risk of Alzheimer's disease or by improving insulin resistance in the brain. Though it is generally safe when used as prescribed, liraglutide may cause gastrointestinal side effects.

Evidence

There is limited clinical evidence on liragultide in Alzheimer's patients. Our search identified:

• One preliminary randomized controlled trial in patients with Alzheimer's disease
• Several meta-analyses for type 2 diabetes and obesity
• Multiple preclinical studies in aging and Alzheimer's disease

Potential Benefit

Meta-analyses of human studies reported that liraglutide was able to control type 2 diabetes and benefit patients with obesity [1][2], which are risk factors for Alzheimer's disease. However, at this time there is no adequate clinical trial data showing that liraglutide is beneficial for prevention of Alzheimer's disease or other dementias.

Preclinical studies suggest that liraglutide does reach the brain and may have many benefits including improved cognition, increased production of new neurons, decreased biological markers of Alzheimer's disease, decreased inflammation, and decreased brain cell death [3-14]. These benefits were seen when the drug was given in early and late stages of the disease [9][10][14].However, another study reported contradictory results, with no benefits after liraglutide treatment [15]. The reason for these contradictory results is unclear.

For Dementia Patients

A small randomized controlled trial in patients with Alzheimer's disease reported that a 26 week treatment with liraglutide did not improve cognition or reduce amyloid plaques. However, it did prevent a decline in brain metabolism [16], which could allow brain cells to function longer.

Safety

Liraglutide is generally safe for most people with type 2 diabetes or obesity, although it is associated with an increased risk of gastrointestinal symptoms (such as nausea and diarrhea) and gallstones [17][18]. Preclinical studies suggest some concerns over chronic use and pancreatitis or thyroid cancer, but meta-analyses of previous studies do not show an increased risk [18-20]. But there are no long-term studies in healthy adults, so an increased risk with long-term use cannot be discounted.

Liraglutide should not be taken with other drugs that can cause hypoglycemia (such as insulin and gatifloxacin) or bexarotene (which can increase the risk of pancreatitis). It can also slightly increase resting heart rate so should be taken with caution in patients with cardiovascular disease [17]. Liraglutide is not recommended for pregnant or breastfeeding women.

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

Liraglutide is available by prescription to treat type 2 diabetes. It can be administered at home with a subcutaneous injection. Typical doses start at 0.6 mg/day for one week and increased to 1.2-1.8 mg/day.

Learn More

The Alzheimer's Drug Discovery Foundation is currently funding a clinical trial being conducted by Dr. Paul Edison to test liraglutide in patients with Alzheimer's disease.

For additional safety and drug interactions, see Drugs.com.

References

  1. Shyangdan DS, Royle P, Clar C et al. (2011) Glucagon-like peptide analogues for type 2 diabetes mellitus. The Cochrane database of systematic reviews, CD006423.
  2. Khera R, Murad MH, Chandar AK et al. (2016) Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis. JAMA : the journal of the American Medical Association 315, 2424-2434.
  3. McClean PL, Gault VA, Harriott P et al. (2010) Glucagon-like peptide-1 analogues enhance synaptic plasticity in the brain: a link between diabetes and Alzheimer's disease. European journal of pharmacology 630, 158-162.
  4. Han WN, Holscher C, Yuan L et al. (2013) Liraglutide protects against amyloid-beta protein-induced impairment of spatial learning and memory in rats. Neurobiology of aging 34, 576-588.
  5. Qi L, Ke L, Liu X et al. (2016) Subcutaneous administration of liraglutide ameliorates learning and memory impairment by modulating tau hyperphosphorylation via the glycogen synthase kinase-3beta pathway in an amyloid beta protein induced alzheimer disease mouse model. European journal of pharmacology 783, 23-32.
  6. Xiong H, Zheng C, Wang J et al. (2013) The neuroprotection of liraglutide on Alzheimer-like learning and memory impairment by modulating the hyperphosphorylation of tau and neurofilament proteins and insulin signaling pathways in mice. Journal of Alzheimer's disease : JAD 37, 623-635.
  7. Hansen HH, Fabricius K, Barkholt P et al. (2015) The GLP-1 Receptor Agonist Liraglutide Improves Memory Function and Increases Hippocampal CA1 Neuronal Numbers in a Senescence-Accelerated Mouse Model of Alzheimer's Disease. Journal of Alzheimer's disease : JAD 46, 877-888.
  8. Hansen HH, Barkholt P, Fabricius K et al. (2016) The GLP-1 receptor agonist liraglutide reduces pathology-specific tau phosphorylation and improves motor function in a transgenic hTauP301L mouse model of tauopathy. Brain Res 1634, 158-170.
  9. McClean PL, Jalewa J, Holscher C (2015) Prophylactic liraglutide treatment prevents amyloid plaque deposition, chronic inflammation and memory impairment in APP/PS1 mice. Behavioural brain research 293, 96-106.
  10. McClean PL, Parthsarathy V, Faivre E et al. (2011) The diabetes drug liraglutide prevents degenerative processes in a mouse model of Alzheimer's disease. The Journal of neuroscience : the official journal of the Society for Neuroscience 31, 6587-6594.
  11. Long-Smith CM, Manning S, McClean PL et al. (2013) The diabetes drug liraglutide ameliorates aberrant insulin receptor localisation and signalling in parallel with decreasing both amyloid-beta plaque and glial pathology in a mouse model of Alzheimer's disease. Neuromolecular medicine 15, 102-114.
  12. Kelly P, McClean PL, Ackermann M et al. (2015) Restoration of cerebral and systemic microvascular architecture in APP/PS1 transgenic mice following treatment with Liraglutide. Microcirculation 22, 133-145.
  13. Chen S, Sun J, Zhao G et al. (2017) Liraglutide Improves Water Maze Learning and Memory Performance While Reduces Hyperphosphorylation of Tau and Neurofilaments in APP/PS1/Tau Triple Transgenic Mice. Neurochemical research.
  14. McClean PL, Holscher C (2014) Liraglutide can reverse memory impairment, synaptic loss and reduce plaque load in aged APP/PS1 mice, a model of Alzheimer's disease. Neuropharmacology 76 Pt A, 57-67.
  15. Hansen HH, Fabricius K, Barkholt P et al. (2016) Long-Term Treatment with Liraglutide, a Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist, Has No Effect on beta-Amyloid Plaque Load in Two Transgenic APP/PS1 Mouse Models of Alzheimer's Disease. PloS one 11, e0158205.
  16. Gejl M, Gjedde A, Egefjord L et al. (2016) In Alzheimer's Disease, 6-Month Treatment with GLP-1 Analog Prevents Decline of Brain Glucose Metabolism: Randomized, Placebo-Controlled, Double-Blind Clinical Trial. Frontiers in aging neuroscience 8, 108.
  17. Marso SP, Daniels GH, Brown-Frandsen K et al. (2016) Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. The New England journal of medicine 375, 311-322.
  18. Monami M, Nreu B, Scatena A et al. (2017) Safety issues with Glucagon-Like peptide-1 receptor agonists: Pancreatitis, pancreatic cancer, and cholelithiasis. data from randomised controlled trials. Diabetes, obesity & metabolism.
  19. Alves C, Batel-Marques F, Macedo AF (2012) A meta-analysis of serious adverse events reported with exenatide and liraglutide: acute pancreatitis and cancer. Diabetes Res Clin Pract 98, 271-284.
  20. Gallo M (2013) Thyroid safety in patients treated with liraglutide. J Endocrine Invest 36, 140-145.