Joanne Salas1,2, John E Morley3, Jeffrey F Scherrer1,2, James S Floyd4,5,6, Susan A Farr3,7, Max Zubatsky1, Doug Barthold8, Sascha Dublin6,9. 1. Department of Family and Community Medicine, Saint Louis University School of Medicine, St. Louis, Missouri, USA. 2. Harry S. Truman Veterans Administration Medical Center, Research Service, Columbia, Missouri, USA. 3. Division of Geriatric Medicine, Saint Louis University School of Medicine, St. Louis, Missouri, USA. 4. Department of Medicine, University of Washington, Seattle, Washington, USA. 5. Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA. 6. Department of Epidemiology, University of Washington, Seattle, Washington, USA. 7. Saint Louis Veterans Affairs Medical Center, Research Service, John Cochran Division, St. Louis, Missouri, USA. 8. Department of Pharmacy, University of Washington, Seattle, Washington, USA. 9. Kaiser Permanente Washington Health Research Institute, Seattle, Washington, USA.
Abstract
PURPOSE: Emerging evidence suggests metformin compared with sulfonylurea is associated with an 8% to 10% lower risk for dementia. Guidelines recommend metformin as initial diabetes treatment, but there is still the question of treatment timing. Thus, the risk of dementia associated with initiating metformin compared with not initiating or delaying treatment was examined. METHODS: A retrospective cohort study (1996 to 2015) was conducted with electronic health records from Veteran Health Affairs (VHA; n = 112 845) and Kaiser Permanente Washington (KPW; n = 14 333) healthcare systems. Patients were aged ≥50 years, had a hemoglobin A1c (HbA1c) between 6.5 and <9.5 mg/dL, and did not have dementia or fills for antidiabetic medications before cohort entry. Initiators started metformin monotherapy and noninitiators used no antidiabetic medications in the 6 months after the first qualifying HbA1c. The primary outcome was incident dementia. Propensity scores and inverse probability of treatment weighting (IPTW) controlled for confounding in Cox proportional hazards models. RESULTS: During a median follow-up of 6.2 years in VHA and 6.8 years in KPW, there were 7547 new dementia cases in VHA and 1090 in KPW. After IPTW, there was no association between initiation of metformin (vs no initial treatment) and incident dementia in VHA (HR = 1.04; 95% confidence interval [CI]: 0.95-1.13) or KPW (HR = 0.81; 95% CI: 0.51-1.28). Results did not differ by age, baseline HbA1c, or race. CONCLUSIONS: Results do not support initiating metformin earlier to prevent cognitive decline and, thus, may dampen enthusiasm for metformin as a potential antidementia drug. Randomized clinical trials could help clarify the relationship between metformin and cognitive decline.
PURPOSE: Emerging evidence suggests metformin compared with sulfonylurea is associated with an 8% to 10% lower risk for dementia. Guidelines recommend metformin as initial diabetes treatment, but there is still the question of treatment timing. Thus, the risk of dementia associated with initiating metformin compared with not initiating or delaying treatment was examined. METHODS: A retrospective cohort study (1996 to 2015) was conducted with electronic health records from Veteran Health Affairs (VHA; n = 112 845) and Kaiser Permanente Washington (KPW; n = 14 333) healthcare systems. Patients were aged ≥50 years, had a hemoglobin A1c (HbA1c) between 6.5 and <9.5 mg/dL, and did not have dementia or fills for antidiabetic medications before cohort entry. Initiators started metformin monotherapy and noninitiators used no antidiabetic medications in the 6 months after the first qualifying HbA1c. The primary outcome was incident dementia. Propensity scores and inverse probability of treatment weighting (IPTW) controlled for confounding in Cox proportional hazards models. RESULTS: During a median follow-up of 6.2 years in VHA and 6.8 years in KPW, there were 7547 new dementia cases in VHA and 1090 in KPW. After IPTW, there was no association between initiation of metformin (vs no initial treatment) and incident dementia in VHA (HR = 1.04; 95% confidence interval [CI]: 0.95-1.13) or KPW (HR = 0.81; 95% CI: 0.51-1.28). Results did not differ by age, baseline HbA1c, or race. CONCLUSIONS: Results do not support initiating metformin earlier to prevent cognitive decline and, thus, may dampen enthusiasm for metformin as a potential antidementia drug. Randomized clinical trials could help clarify the relationship between metformin and cognitive decline.
Authors: Timothy L Wiemken; Joanne Salas; John E Morley; Daniel F Hoft; Christine Jacobs; Jeffrey F Scherrer Journal: J Am Geriatr Soc Date: 2021-12-12 Impact factor: 7.538