Antidiabetic Drugs for the Risk of Alzheimer Disease in Patients With Type 2 DM Using FAERS

Abstract

Alzheimer disease (AD) may develop after the onset of type 2 diabetes mellitus (T2DM), and the risk of AD may depend on the antidiabetic drug administered. We compared the risk of AD among 66 085 patients (≥ 65 years) with T2DM (1250 having concomitant AD) who had been administered antidiabetic drug monotherapy for T2DM who had voluntarily reported themselves in the Food and Drug Administration Adverse Event Reporting System. The risk of AD from the use of different antidiabetic drug monotherapies compared to that of metformin monotherapy was assessed by logistic regression. Rosiglitazone (adjusted reporting odds ratio [aROR] = 0.11; 95% confidence interval [CI]: 0.07-0.17; P < .001), exenatide (aROR = 0.22; 95% CI: 0.11-0.37; P < .001), liraglutide (aROR = 0.36; 95% CI: 0.19-0.62; P < .001), dulaglutide (aROR = 0.39; 95% CI: 0.17-0.77; P = .014), and sitagliptin (aROR = 0.75; 95% CI: 0.60-0.93; P = .011) were found to have a significantly lower associated risk of AD than that of metformin. Therefore, the administration of glucagon-like peptide 1 receptor agonists and rosiglitazone may reduce the risk of AD in patients with T2DM.

Keywords: Alzheimer disease; FDA adverse event reporting system; antidiabetics; dementia; type 2 diabetes mellitus.

Figure 1.

Flowchart of patient data selection for risk assessment. AD indicates Alzheimer disease; FAERS, Food and Drug Administration Adverse Event Reporting System.

Figure 2.

Risk of development of Alzheimer disease using the different antidiabetic drug therapies compared to metformin. Lixisenatide was excluded from the analysis since no relevant cases were extracted (Table 2). Antidiabetic drugs for which there were 0 patients with concomitant Alzheimer disease (chlorpropamide, tolazamide, albiglutide, canagliflozin, and dapagliflozin) were not included in this figure since the adjusted reporting odds ratio (aROR) could not be accurately calculated, and there was a large variance.

Figure 3.

Risk associated with the development of Alzheimer disease with the use of different antidiabetic drug therapies in male patients. Lixisenatide was excluded from the analysis, since no relevant cases were extracted (Table 2). Antidiabetic drugs for which there were 0 patients with concomitant Alzheimer disease (acarbose, chlorpropamide, tolazamide, albiglutide, canagliflozin, and dapagliflozin) are not included in this figure since the adjusted reporting odds ratio (aROR) could not be accurately calculated and large variance was present.

Figure 4.

Risk associated with the development of Alzheimer disease with the use of different antidiabetic drug therapies in female patients. Lixisenatide was excluded from the analysis since no relevant cases were extracted (Table 2). Antidiabetic drugs for which there were 0 patients with concomitant Alzheimer disease (chlorpropamide, tolazamide, tolbutamide, albiglutide, canagliflozin, and dapagliflozin) are not included in this figure, as the adjusted reporting odds ratio (aROR) could not be accurately calculated and large variance was present.