Dementia Risk in Type 2 Diabetes Patients: Acarbose Use and Its Joint Effects with Metformin and Pioglitazone

Abstract

This population-based retrospective cohort study investigated dementia risk associated with acarbose in patients with type 2 diabetes mellitus by using Taiwan's National Health Insurance database. A cohort of 15,524 matched pairs of ever and never users of acarbose based on propensity score matching was enrolled from new-onset type 2 diabetes patients from 1999 to 2006. Patients who were alive on January 1, 2007, were followed up for dementia until December 31, 2011. Adjusted hazard ratios were estimated using Cox proportional hazards models. The results revealed that the incident case numbers (incidence rates) of dementia were 264 (407.19 per 100,000 person-years) for never users and 231 (337.94 per 100,000 person-years) for ever users. The hazard ratio for ever users versus never users was 0.841 (95% confidence interval, 0.704-1.005) and 0.918 (0.845-0.998) for every 1-year increment of cumulative duration of acarbose therapy. Subgroup analyses showed that the reduced risk associated with acarbose was only observed in women (adjusted hazard ratio, 0.783; 95% confidence interval, 0.618-0.992) and in non-users of metformin (adjusted hazard ratio, 0.635; 95% confidence interval, 0.481-0.837). A model comparing different combinations of acarbose, metformin, and pioglitazone suggested that users of all three drugs had the lowest risk of dementia (hazard ratio, 0.406; 95% confidence interval, 0.178-0.925). In conclusion, reduced risk of dementia associated with acarbose is observed in the female sex and in non-users of metformin. Moreover, users of all three drugs (acarbose, metformin, and pioglitazone) have the lowest risk of dementia.

The Effect of Metformin on Male Reproductive Function and Prostate: An Updated Review

“…Heart failure [ 34 ], atrial fibrillation [ 35 ], chronic obstructive pulmonary disease [ 36 ], osteoporosis [ 37 ], dementia [ 38 ], inflammatory bowel diseaese [ 39 ], and varicocele [ 40 ] have been associated with a higher incidence of ED in humans. Except for varicocele, our previous analyses supported a lower risk of all these morbidities among metformin users [ 6 7 8 11 12 15 16 ]. Although the effect of metformin on varicocele has not been studied, it is highly possible that metformin may reduce the risk of varicocele (another form of venous dilatation involving the testicles) because metformin has been shown to reduce the risk of venous diseases of varicose veins [ 9 ] and hemorrhoid [ 10 ].…”

“…Metformin exerts various beneficial effects beyond glucose lowering, including immune modulation, anti-atherosclerosis, anti-cancer, anti-aging, anti-microbia, and anti-inflammation [ 3 4 ]. Recently, by using the nation-wide database of the National Health Insurance in Taiwan, we also showed that metformin use is associated with a lower risk of hypertension [ 5 ], hospitalization for heart failure [ 6 ], hospitalization for atrial fibrillation [ 7 ], chronic obstructive pulmonary disease [ 8 ], varicose veins [ 9 ], hemorrhoid [ 10 ], dementia [ 11 12 ], nodular goiter [ 13 ], uterine leiomyoma [ 14 ], osteoporosis/vertebral fracture [ 15 ], and inflammatory bowel disease [ 16 ].…”

Pioglitazone and breast cancer risk in female patients with type 2 diabetes mellitus: a retrospective cohort analysis

“…First, together with our previous studies that do not suggest an increased risk of bladder cancer [ 30 ], ovarian cancer [ 31 ], oral cancer [ 32 ], kidney cancer [ 33 ], thyroid cancer [ 34 ], lung cancer [ 35 ] and prostate cancer [ 36 ] associated with pioglitazone use, the public health concern of an increased cancer risk associated with pioglitazone can be relieved and should not impede the clinical use of pioglitazone. Second, the potential benefits of pioglitazone on the improvement of lipid profile [ 37 ], the risk reduction of dementia [ 38 , 39 ], chronic obstructive pulmonary disease [ 40 ], non-alcoholic fatty liver disease [ 41 ], stroke [ 2 ] and cardiovascular disease [ 42 ] and the usefulness of pioglitazone in the treatment of polycystic ovarian syndrome in women [ 43 ] suggest that some patients may gain pleiotropic benefits beyond glycemic control from the appropriate use of pioglitazone.…”

Metformin and Risk of Malignant Brain Tumors in Patients with Type 2 Diabetes Mellitus

“…As pointed out by a recent article discussed by Baker et al, up to now, "there are no data to suggest that metformin should not be initiated soon after the diagnosis of diabetes", even in the era of these novel antidiabetic drugs [56]. Our previous pharmaco-epidemiological studies conducted in Taiwan suggest that metformin not only reduces cancer risk, but also the risk of various non-malignant diseases such as hypertension [58], heart failure [59], atrial fibrillation [60], chronic obstructive pulmonary disease [61], pulmonary tuberculosis infection [62], Helicobacter pylori infection [63], varicose veins [64], acute appendicitis [65], hemorrhoids [66], dementia [67,68], nodular goiter [69], uterine leiomyoma [70], osteoporosis/vertebral fracture [71], and inflammatory bowel disease [72]. We also found that metformin ever users have a lower risk of total mortality than never users of metformin, with an estimated multivariate-adjusted hazard ratio of 0.67 (95% confidence interval: 0.64-0.69) [72].…”