Metformin and the risk of neurodegenerative diseases in patients with diabetes: A meta‐analysis of population‐based cohort studies

Abstract

The association between metformin use and neurodegenerative disease (ND) onset remains controversial. In this systematic review and meta-analysis, we aimed to determine the relationship between metformin use and ND risk based on data from population-based cohort studies.Methods: Articles were systematically searched in PubMed, EMBASE and Cochrane Library databases. Pooled relative risks (RRs) with 95% CIs were obtained using a random-effects model. Subgroup analyses, sensitivity analyses and meta-regression were performed to identify the sources of heterogeneity and strengthen the results.Results: Twelve population-based cohort studies involving 194,792 participants (94,462 metformin users and 100,330 metformin non-users) were eligible for inclusion in this meta-analysis. The pooled RR of NDs reached 0.77 (95% CI 0.67-0.88) when comparing metformin users with non-users. The effects were more prominent in long-term metformin users (≥4 years) (RR 0.29, 95% CI 0.13-0.44) and studies from Asian countries (RR 0.69, 95% CI 0.64-0.74). The effect estimates were stable when stratified by subtypes of NDs, study designs, and control definitions (p for interaction >0.05). Meta-regression did not identify the coefficients as the sources of heterogeneity (all p > 0.05). Conclusions:This systematic review and meta-analysis found that metformin use, especially long-term use, was associated with lower ND risk. However, because there was substantial heterogeneity among studies, high-quality randomized controlled trials are still needed to confirm this finding.

Metformin: Is it a drug for all reasons and diseases?

“…The results from a systematic review published in 2020 that was based on 23 comparisons of 19 studies and over 250,000 subjects concluded that there was no benefit associated with the use of metformin and for Parkinson's and, in fact, metformin may worsen the risk for Parkinson's [362]. In contrast, a 2022 systematic review and meta-analysis of 94,462 metformin users versus 100,330 non-users concluded that longterm (≥ 4 years) treatment with metformin was associated with a lower risk of neurodegenerative disease, and particularly in Asiatic populations [363].…”

It’s complicated

“…A metaanalysis of the impact of metformin on neurodegenerative disease suggests that metformin use, and in particular longer term use of the drug, is associated with a reduced risk of neurodegenerative disease. 6 This is an important finding as it is rapidly implementable in clinical practicemetformin is universally available, is a lower-cost drug, has a well-established safety profile and an inclusive set of indications that mean that, contrary to new or experimental therapeutics, it can be delivered rapidly. Long-term randomised controlled trials would be beneficial but may not report for many years while implementing existing agents is more acceptable and feasible, though this must be accompanied by robust data collection to assess impact.…”

“…Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, dementia and cognitive disorders are more common in people with diabetes and a portfolio of effective treatment strategies is required to meet the rising prevalence. A meta‐analysis of the impact of metformin on neurodegenerative disease suggests that metformin use, and in particular longer term use of the drug, is associated with a reduced risk of neurodegenerative disease 6 . This is an important finding as it is rapidly implementable in clinical practice—metformin is universally available, is a lower‐cost drug, has a well‐established safety profile and an inclusive set of indications that mean that, contrary to new or experimental therapeutics, it can be delivered rapidly.…”

Efficacy and safety of metformin in adjuvant chemotherapy for non-diabetic tumor patients： Systematic review and Meta-analysis

“…In addition, metformin use has been associated in observational studies with a reduced risk of developing tumors in patients with type 2 diabetes mellitus [10][11][12][13]. Meta-analyses have also shown that metformin use is associated with a reduced risk of tumorigenesis [14,15]. Diabetes is closely related to the prognosis of tumor patients.…”

“…Diabetes was also associated with an increased risk of some tumors [17,18]. Metformin use has been shown to be associated with better outcomes in cancer patients, and metformin use has been shown to prolong progression-free survival and overall survival [19,20] (14,18,19). Although some data suggest that metformin has an anticancer effect, some studies have questioned its anticancer effect, suggesting that metformin use is not associated with patient outcome [21].…”