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Name: Semaglutide
Synonyms: Ozempic, Rybelsus
Therapy Type: Other
Target Type: Other (timeline)
Condition(s): Alzheimer's Disease, Parkinson's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 3), Parkinson's Disease (Phase 2)
Company: Novo Nordisk A/S
Approved for: Type 2 Diabetes


Semaglutide is a synthetic, long-acting analog of glucagon-like peptide-1, used to treat diabetes. OzempicTM is a once-per-week injection formulation, while RybelsusTM is is a daily pill. RybelsusTM was approved by the U.S. FDA in September 2019 as the first GLP-1 analog that does not need to be injected. It is also approved for use in Japan and the European Union.

GLP-1 is a hormone produced in the gut that activates receptors in the gut, liver, and pancreas to stimulate insulin release, and restore insulin sensitivity (for review, see Knudsen and Lau, 2019). In some people with Alzheimer’s disease, there is evidence for insulin resistance in the brain, providing a rationale for testing semaglutide as a potential therapeutic for AD. In addition, GLP-1 receptors expressed in the brain are involved in learning and neuroprotection (During et al., 2003). Other GLP-1 analogs, for example exendin-4 and liraglutide, are currently in clinical trials for Parkinson’s or Alzheimer’s diseases.

There are few published preclinical studies for semaglutide in Alzheimer’s. A cell-based study implicated the drug in enhanced autophagy and reduced apoptosis (Chang et al., 2020). In 3xTg mouse model of AD, semaglutide improved brain glucose uptake, improved learning and memory, and decreased Aβ plaques and tau tangles (Wang et al., 2023). The drug is reported to be active in rodent models of Parkinson’s (Zhang et al., 2019; Zhang et al., 2018) and stroke (Yang et al., 2019). Semaglutide does not cross the blood brain barrier (Salameh et al., 2020; Lee et al., 2023). It is thought to act by lowering peripheral blood sugar, and reducing peripheral and central inflammation.


In September 2018, researchers at the University of Oslo registered a Phase 2 trial of semaglutide for Parkinson’s disease. The study aims to enroll 120 newly diagnosed PD patients who will receive 1 mg drug or placebo by weekly injection for two years, followed by an additional two years of open-label administration. As of February 2023, the trial had not begun recruiting.

A Phase 2a trial of semaglutide tablets in 60 people with mild Alzheimer's disease has received funding from the Alzheimer's Association's Part the Cloud program, but is not registered.

On December 16, 2020, Novo Nordisk announced it would begin development of semaglutide in people with early Alzheimer’s disease (see press release). Beginning in the first half of 2021, the Phase 3a program planned to enroll 3,700 people for a planned two-year course of a once-daily 14 mg semaglutide pill or placebo. The company said the decision was based on evaluation of GLP-1 data from preclinical models, real-world studies involving patient registry and insurance claims databases, and post hoc analysis of data from three large cardiovascular outcome trials of semaglutide and liraglutide. That analysis reportedly found a 53 percent reduction in the risk of developing dementia in people with Type 2 diabetes who took either GLP-1 agonist compared to placebo placebo (see Nørgaard et al., 2022).

In May 2021, the company began two Phase 3 trials, each enrolling 1,840 people with mild cognitive impairment or mild dementia due to Alzheimer’s disease, confirmed by amyloid PET or CSF Aβ42. The trials are identical, except that one allows participants with subcortical vascular disease, and one does not. The sole primary outcome is change in CDR-SB. Secondary outcomes include other standard cognitive and functional scales, as well as cardiovascular events and stroke. The trials include a one-year extension. By mid-2023, both studies were fully enrolled and running at more than 400 centers worldwide, to be completed in October 2026.

In August 2022 enrollment began on a study evaluating the effect of semaglutide on tau accumulation in the brains of people who are amyloid-positive, with or without diabetes, and with no or mild cognitive impairment. The study at the University of Oxford in the U.K., will treat 88 participants with a dose of 14 mg once daily oral semaglutide or placebo for one year, against a primary outcome of change in tau-PET. Secondary outcomes address potential mechanism of semaglutide action, including brain inflammation measured by TSPO-PET and GFAP protein levels, and blood biomarkers of Aβ, phosphorylated tau and neurofilament light. Other outcomes are hippocampal volume by MRI, cognition, quality of life, physical activity, and circadian rhythms. Supported by Novo Nordisk, the trial is expected to finish in November 2024.

In January 2023, a small, placebo-controlled study was to begin China. Enrolling 68 patients, it assesses the effect of semaglutide on the CDR-SB and diabetes outcomes, and is to run through 2025.

In June 2023, Novo Nordisk began a small study on how semaglutide affects the immune system in people with Alzheimer’s. Twenty-four participants will receive 12 weekly subcutaneous injections with a pen injector, titrating to a final dose of 1 mg per week. After a 12-week placebo-controlled period, all participants will receive 1 mg/week for one year open-label. The primary endpoint is changes in gene expression in immune cells in blood and CSF, assessed by single-cell RNA sequencing. Secondaries are safety, and semaglutide concentration in blood. Study completion is anticipated in June 2025.

For details on these semaglutide trials, see, the WHO registry, and the Chinese clinical trial registry.

Last Updated: 16 Oct 2023


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Therapeutics Citations

  1. Liraglutide

Paper Citations

  1. . Treatment with glucagon-like peptide-1 receptor agonists and incidence of dementia: Data from pooled double-blind randomized controlled trials and nationwide disease and prescription registers. Alzheimers Dement (N Y). 2022;8(1):e12268. Epub 2022 Feb 23 PubMed.
  2. . The Discovery and Development of Liraglutide and Semaglutide. Front Endocrinol (Lausanne). 2019;10:155. Epub 2019 Apr 12 PubMed.
  3. . Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med. 2003 Sep;9(9):1173-9. PubMed.
  4. . Semaglutide-mediated protection against Aβ correlated with enhancement of autophagy and inhibition of apotosis. J Clin Neurosci. 2020 Nov;81:234-239. Epub 2020 Oct 14 PubMed.
  5. . Semaglutide ameliorates cognition and glucose metabolism dysfunction in the 3xTg mouse model of Alzheimer's disease via the GLP-1R/SIRT1/GLUT4 pathway. Neuropharmacology. 2023 Dec 1;240:109716. Epub 2023 Sep 18 PubMed.
  6. . Semaglutide is Neuroprotective and Reduces α-Synuclein Levels in the Chronic MPTP Mouse Model of Parkinson's Disease. J Parkinsons Dis. 2019;9(1):157-171. PubMed.
  7. . Neuroprotective effects of the novel GLP-1 long acting analogue semaglutide in the MPTP Parkinson's disease mouse model. Neuropeptides. 2018 Oct;71:70-80. Epub 2018 Jul 11 PubMed.
  8. . The diabetes drug semaglutide reduces infarct size, inflammation, and apoptosis, and normalizes neurogenesis in a rat model of stroke. Neuropharmacology. 2019 Nov 1;158:107748. Epub 2019 Aug 26 PubMed.
  9. . Brain uptake pharmacokinetics of incretin receptor agonists showing promise as Alzheimer's and Parkinson's disease therapeutics. Biochem Pharmacol. 2020 Oct;180:114187. Epub 2020 Aug 2 PubMed. Correction.
  10. . Novel LC-MS/MS analysis of the GLP-1 analog semaglutide with its application to pharmacokinetics and brain distribution studies in rats. J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Apr 15;1221:123688. Epub 2023 Mar 22 PubMed.

Other Citations

  1. exendin-4

External Citations

  1. Phase 2 trial
  2. Part the Cloud program
  3. press release
  5. WHO registry
  6. Chinese clinical trial registry

Further Reading


  1. . Effects of glucagon-like peptide 1 receptor agonists on comorbidities in older patients with diabetes mellitus. Ther Adv Chronic Dis. 2019;10:2040622319862691. Epub 2019 Jul 12 PubMed.
  2. . Diabetes, insulin and new therapeutic strategies for Parkinson's disease: Focus on glucagon-like peptide-1 receptor agonists. Front Neuroendocrinol. 2021 Jul;62:100914. Epub 2021 Apr 15 PubMed.
  3. . An extended release GLP-1 analogue increases α-synuclein accumulation in a mouse model of prodromal Parkinson's disease. Exp Neurol. 2021 Jul;341:113693. Epub 2021 Mar 13 PubMed.
  4. . GLP-1 receptor agonists for Parkinson's disease. Cochrane Database Syst Rev. 2020 Jul 23;7:CD012990. PubMed.