PMID- 36849855
OWN - NLM
STAT- MEDLINE
DCOM- 20230601
LR  - 20230601
IS  - 1568-5608 (Electronic)
IS  - 0925-4692 (Linking)
VI  - 31
IP  - 3
DP  - 2023 Jun
TI  - Long-term use of metformin and Alzheimer's disease: beneficial or detrimental 
      effects.
PG  - 1107-1115
LID - 10.1007/s10787-023-01163-7 [doi]
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disease 
      characterized by extracellular deposition of amyloid beta (Abeta) leading to 
      cognitive decline. Evidence from epidemiological studies has shown the 
      association between type 2 diabetes mellitus (T2DM) and the development of AD. 
      T2DM and peripheral insulin resistance (IR) augment the risk of AD with the 
      development of brain IR with inhibition of neuronal insulin receptors. These 
      changes impair clearance of Abeta, increase secretion of Abeta(1-42), reduce brain 
      glucose metabolism, and abnormal deposition of Abeta plaques. Insulin-sensitizing 
      drug metformin inhibits aggregation of Abeta by increasing the activity of the 
      insulin-degrading enzyme (IDE) and neprilysin (NEP) levels. Additionally, 
      different studies raised conflicting evidence concerning long-term metformin 
      therapy in T2DM patients, as it may increase the risk of AD or it may prevent the 
      progression of AD. Therefore, the objective of this review was to clarify the 
      beneficial and detrimental effects of long-term metformin therapy in T2DM 
      patients and risk of AD. Evidence from clinical trial studies revealed the little 
      effect of metformin on AD. Various animal studies showed that metformin increases 
      Abeta formation by activation of amyloid precursor protein (APP)-cleaving enzymes 
      with the generation of insoluble tau species. Of note, the metformin effect on 
      cognitive function relative to AD pathogenesis is mostly assessed in animal model 
      studies. The duration of metformin therapy was short in most animal studies, this 
      finding cannot apply to the long-term duration of metformin in humans. Therefore, 
      large-scale prospective and comparative studies involving long-term metformin 
      therapy in both diabetic and non-diabetic patients are required to exclude the 
      effect of T2DM-induced AD.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
FAU - Al-Kuraishy, Hayder M
AU  - Al-Kuraishy HM
AD  - Department of Pharmacology, Toxicology and Medicine, Medical Faculty, College of 
      Medicine, Al-Mustansiriyah University, P.O. Box 14132, Baghdad, Iraq.
FAU - Al-Gareeb, Ali I
AU  - Al-Gareeb AI
AD  - Department of Pharmacology, Toxicology and Medicine, Medical Faculty, College of 
      Medicine, Al-Mustansiriyah University, P.O. Box 14132, Baghdad, Iraq.
FAU - Saad, Hebatallah M
AU  - Saad HM
AUID- ORCID: 0000-0001-9555-7300
AD  - Department of Pathology, Faculty of Veterinary Medicine, Matrouh University, 
      Marsa Matruh, 51744, Egypt. heba.magdy@mau.edu.eg.
FAU - Batiha, Gaber El-Saber
AU  - Batiha GE
AD  - Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, 
      Damanhour University, Damanhour, 22511, Egypt. gaberbatiha@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20230228
PL  - Switzerland
TA  - Inflammopharmacology
JT  - Inflammopharmacology
JID - 9112626
RN  - 0 (Amyloid beta-Peptides)
RN  - 9100L32L2N (Metformin)
RN  - 0 (Insulin)
SB  - IM
MH  - Animals
MH  - Humans
MH  - *Alzheimer Disease/drug therapy/metabolism
MH  - Amyloid beta-Peptides/metabolism
MH  - *Metformin/pharmacology/therapeutic use
MH  - *Diabetes Mellitus, Type 2/drug therapy/metabolism
MH  - *Neurodegenerative Diseases
MH  - Prospective Studies
MH  - Insulin/metabolism
MH  - *Insulin Resistance
MH  - Brain/metabolism
MH  - Disease Models, Animal
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Insulin resistance
OT  - Metformin
EDAT- 2023/03/01 06:00
MHDA- 2023/06/01 06:42
CRDT- 2023/02/28 00:30
PHST- 2023/01/27 00:00 [received]
PHST- 2023/02/10 00:00 [accepted]
PHST- 2023/06/01 06:42 [medline]
PHST- 2023/03/01 06:00 [pubmed]
PHST- 2023/02/28 00:30 [entrez]
AID - 10.1007/s10787-023-01163-7 [pii]
AID - 10.1007/s10787-023-01163-7 [doi]
PST - ppublish
SO  - Inflammopharmacology. 2023 Jun;31(3):1107-1115. doi: 10.1007/s10787-023-01163-7. 
      Epub 2023 Feb 28.