Antidiabetic medication and risk of dementia in patients with type 2 diabetes: a nested case–control study

in European Journal of Endocrinology
Correspondence should be addressed to I K Wium-Andersen; Email: Ida.kim.wiumandersen@regionh.dk
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Objective

Diabetes is a risk factor for dementia, but whether antidiabetic medication decreases the risk is unclear. We examined the association between antidiabetic medication and dementia.

Design

We performed a nested case–control study within a cohort of all 176 250 patients registered with type 2 diabetes in the Danish National Diabetes Register between 1995 and 2012. This population was followed for dementia diagnosis or anti-dementia medication use until May 2018. Using risk-set sampling, each dementia case (n = 11 619) was matched on follow-up time and calender year of dementia with four controls randomly selected among cohort members without dementia (n = 46 476). Ever use and mean daily defined dose of antidiabetic medication was categorized in types (insulin, metformin, sulfonylurea and glinides combined, glitazone, dipeptidyl peptidase 4 (DPP4) inhibitors, glucagon-like peptide 1 (GLP1) analogs, sodium-glucose transport protein 2 (SGLT2) inhibitors and acarbose).

Methods

Conditional logistic regression models were fitted to calculate odds ratios (ORs) for dementia associated with antidiabetic medication use, adjusting for potential confounders.

Results

Use of metformin, DPP4 inhibitors, GLP1 analogs, and SGLT2 inhibitors were associated with lower odds of dementia after multible adjustments (ORs of 0.94 (95% confidence interval (CI): 0.89–0.99), 0.80 (95% CI 0.74–0.88), 0.58 (95% CI: 0.50–0.67), and 0.58 (95% CI: 0.42–0.81), respectively), with a gradual decrease in odds of dementia for each increase in daily defined dose. Analyses of the most frequent treatment regimes did not show any synergistic effects of combined treatment.

Conclusion

Use of metformin, DPP4 inhibitors, GLP1 analogs and SGLT2 inhibitors was associated with lower risk of dementia in patients with diabetes.

Downloadable materials

  • Supplementary Figure 1
  • Supplementary Figure 2
  • Supplementary Table 1. ICD-10 and ATC codes used to define the health.
  • Supplementary Table 2. Combinations of antidiabetic medication.
  • Supplementary Table 3. Main demographic and clinical characteristics of the included patients with type 2 diabetes from the National Diabetes Register based on insulin use.
  • Supplementary Table 4. Main demographic and clinical characteristics of the included patients with type 2 diabetes from the National Diabetes Register based on metformin use.
  • Supplementary Table 5. Main demographic and clinical characteristics of the included patients with type 2 diabetes from the National Diabetes Register based on sulfonylurea use.
  • Supplementary Table 6. Main demographic and clinical characteristics of the included patients with type 2 diabetes from the National Diabetes Register based on glitazone use.
  • Supplementary Table 7. Main demographic and clinical characteristics of the included patients with type 2 diabetes from the National Diabetes Register based on DPP4 inhibitor use.
  • Supplementary Table 8. Main demographic and clinical characteristics of the included patients with type 2 diabetes from the National Diabetes Register based on GLP1 analog use.
  • Supplementary Table 9. Main demographic and clinical characteristics of the included patients with type 2 diabetes from the National Diabetes Register based on SGLT2 inhibitor use.
  • Supplementary Table 10. Main demographic and clinical characteristics of the included patients with type 2 diabetes from the National Diabetes Register based on acarbose use.
  • Supplementary Table 11. Main demographic and clinical characteristics of the included patients with type 2 diabetes from the National Diabetes Register based on combinations of antidiabetics.
  • Supplementary Table 12. Main demographic and clinical characteristics of the included patients with type 2 diabetes from the Danish Adult Diabetes Register.

 

     European Society of Endocrinology

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Figures

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    Flowchart of the study design.

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    Use of antidiabetic medication in type 2 diabetic patients with (cases) or without (controls) dementia during follow-up in the National Diabetes Register, based on 11,619 cases and 46,476 controls. Multiple adjustments include age, sex, education, marital status, year of dementia diagnosis, ischemic heart disease, cerebrovascular disease, clopidogrel/warfarin/aspirin use, hypertension, obesity, hypercholesterolemia, infections, chronic obstructive pulmonary disease, inflammatory disorder, depression, alcohol use disorder, and number of acute and chronic diabetes complications.

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    Previous use of antidiabetic medication in type 2 diabetic patients with (cases) or without (controls) dementia during follow-up in the National Diabetes Register based on 11,619 cases and 46,476 controls. Multifactorial is adjusted for age, sex, education, marital status, year of dementia diagnosis, ischemic heart disease, cerebrovascular disease, clopidogrel/warfarin/aspirin use, hypertension, obesity, hypercholesterolemia, infections, chronic obstructive pulmonary disease, inflammatory disorder, depression, alcohol use disorder, and number of acute and chronic diabetes complications.

  • View in gallery

    Combinations of antidiabetic medication in type 2 diabetic patients with (cases) or without (controls) dementia during follow-up in the National Diabetes Register. Based on 11,619 cases and 46,476 controls. Adjustment for age, sex, education, marital status, year of dementia diagnosis, ischemic heart disease, cerebrovascular disease, clopidogrel/warfarin/aspirin use, hypertension, obesity, hypercholesterolemia, infections, chronic obstructive pulmonary disease, inflammatory disorder, depression, alcohol use disorder, and number of acute and chronic diabetes complications. *The expected point estimates for combined use was calculated using the risk estimates in Figure 1.

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