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Association of metformin use with Alzheimer's disease in patients with newly diagnosed type 2 diabetes: a population-based nested case-control study.

ABSTRACT: Metformin reduces insulin resistance, which constitutes a pathophysiological connection of diabetes with Alzheimer's disease (AD), but the evidence of metformin on AD development was still insufficient and conflicting. We investigated AD risk in patients with newly diagnosed type 2 DM treated with metformin. This retrospective, observational, nested case-control study included patients with newly diagnosed type 2 DM obtained from the Korean National Health Insurance Service DM cohort (2002-2017). Among 70,499 dementia-free DM patients, 1675 AD cases were matched to 8375 controls for age, sex, and DM onset and duration. The association between AD and metformin was analyzed by multivariable regression analyses, adjusted for comorbidities and cardiometabolic risk profile. Metformin use was associated with an increased odds of AD (adjusted odds ratio [AOR] 1.50; 95% CI 1.23-1.83). The risk of AD was higher in patients with a longer DM duration. Furthermore, AD risk was significantly high in DM patients with depression (AOR 2.05; 95% CI 1.02-4.12). Given the large number of patients with DM who are taking metformin worldwide, a double-blinded, prospective study is required to determine the long-term cognitive safety of metformin.

SUBMITTER: Ha J

PROVIDER: S-EPMC8674300 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Association of metformin use with Alzheimer's disease in patients with newly diagnosed type 2 diabetes: a population-based nested case-control study.

Ha Junghee J Choi Dong-Woo DW Kim Kwang Joon KJ Cho So Yeon SY Kim Hyunjeong H Kim Keun You KY Koh Youngseung Y Nam Chung Mo CM Kim Eosu E

Scientific reports 20211215 1

Metformin reduces insulin resistance, which constitutes a pathophysiological connection of diabetes with Alzheimer's disease (AD), but the evidence of metformin on AD development was still insufficient and conflicting. We investigated AD risk in patients with newly diagnosed type 2 DM treated with metformin. This retrospective, observational, nested case-control study included patients with newly diagnosed type 2 DM obtained from the Korean National Health Insurance Service DM cohort (2002-2017) ...[more]

PMID: 34912022

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Project description:ObjectivesHypotension is of particular relevance for patients with heart failure (HF), since almost all HF drugs cause lowering of blood pressure (BP) and it is associated with a poor prognosis. We aimed to investigate hypotension incidence and risk factors in patients with incident HF in the UK.DesignRetrospective cohort study including nested case-control analyses.SettingThe Health Improvement Network UK primary care database.Participants18 677 adult patients with incident HF during 2000-2005 were followed and cases of hypotension (systolic BP ≤90 mm Hg) were identified. Controls were age-matched, sex-matched and date-matched to cases (1:2).Primary and secondary outcome measuresWe estimated hypotension incidence in the full study population and relevant subgroups (eg, sex and age). Potential risk factors for hypotension overall and for multiple versus single hypotensive episodes were evaluated using conditional logistic regression and unconditional regression models, respectively.ResultsDuring a mean follow-up of 3.31 years, 2565 patients (13.7%) developed hypotension. The incidence of hypotension was 3.17 cases per 100 patient years (95% confidence interval (CI): 3.05-3.30), and was markedly increased in women aged 18-39 years (n=32; 17.72 cases per 100 patient-years; 95% CI: 9.69-29.73). Hypotension risk factors included high healthcare utilisation (proxy measure for HF severity and general comorbidity; eg, ≥10 primary care physician visits versus none, odds ratio (OR): 2.29; 95% CI: 1.34-3.90), previous hypotensive episodes (OR: 2.32; 95% CI: 1.84-2.92), renal failure and use of aldosterone antagonists, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Risk factors identified for hypotension generally overlapped with those for multiple versus single hypotensive episodes.ConclusionsHypotension occurs frequently in patients with incident HF. Our findings may help identify patients most likely to benefit from close BP monitoring. The increased incidence of hypotension in young women with HF requires investigation.

Project description:OBJECTIVE:To assess the efficacy and safety of short- term intensive hypoglycemic therapy with a triple regimen consisting of metformin, sagliptin and dapagliflozin in patients with newly diagnosed type 2 diabetes mellitus with hemoglobin Alc (HbA1c) of 9%-12%. METHODS:We prospectively enrolled 58 patients with newly diagnosed type 2 diabetes, who were treated with metformin combined with sagliptin and dapagliflozin for 12 weeks on the basis of diabetic diet and regular exercise. Blood glucose was monitored during the treatment and the changes in HbA1c, fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 hPBG), fasting insulin (FINS), 2-hour postprandial insulin (2 hPINS), fasting C-peptide (F-CP), 2-hour postprandial C-peptide (2 hP-CP), and body weight after treatment as well as the incidence of hypoglycemia and adverse events associated with the treatment were recorded. RESULTS:Two patients withdrew from the study for intolerance of gastrointestinal reactions, and another 2 withdrew for inconvenience of access to the medicines. Fifty-four of the patients finally completed the study, including 34 male and 20 female patients. After 12 weeks of therapy, all the patients showed significant improvements in FBG, 2 hPBG, HbA1c, HOMA-beta and HOMA-IR (P < 0.001) with a mean reduction of HbA1c level by (4.19 ± 1.07)%, and the goal of HbA1c control to below 7.0% was achieved in 83.33% of the patients. The reduction of HbA1c was correlated with FBG (r=0.487, P=0.000), 2 hPBG (r=0.310, P=0.023), and HOMA-? (r=-0.398, P=0.003). The patients had a mean body weight loss by 2.47±3.38 kg (P < 0.001) and a mean decrease of body mass index (BMI) by 0.90± 1.18 kg/m2 (P < 0.001) after the therapy. The body weight-reducing effect was associated with the patients' baseline body weight (r=0.678, P=0.000), BMI (r=0.818, P=0.000), F-CP (r=0.282, P=0.039) and HOMA-IR (r=0.297, P=0.029). During the therapy 8 patients experienced hypoglycemic symptoms (10 times, 14.81%); 3 patients were diagnosed with hypoglycemia (blood glucose ?3.9 mmol/L, 3 times), and the overall incidence of hypoglycemia was 5.56%. No serious hypoglycemia or infections of the urinary and reproductive systems occurred in these patients. CONCLUSIONS:Short-term intensive oral hypoglycemic therapy with metformin combined with sagliptin and dapagliflozin is effective for treatment of patients with newly diagnosed type 2 diabetes with HbA1c of 9%-12% and shows a good weight-reducing effect with a low risk of hypoglycemia. The combined therapy can effectively improve ?-cell insulin secretion function, and is suitable for treatment of newly diagnosed type 2 diabetic patients with high blood glucose.

Dataset Information

Association of metformin use with Alzheimer's disease in patients with newly diagnosed type 2 diabetes: a population-based nested case-control study.

Publications

Association of metformin use with Alzheimer's disease in patients with newly diagnosed type 2 diabetes: a population-based nested case-control study.

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