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Sodium-Glucose Cotransporter-2 Inhibitors, Dulaglutide, and Risk for Dementia : A Population-Based Cohort Study
Bin Hong1, Sungho Bea2, Hwa Yeon Ko1
1School of Pharmacy, Sungkyunkwan University, Suwon, South Korea (B.H., H.Y.K.).
Background:
Both sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may have neuroprotective effects in patients with type 2 diabetes (T2D). However, their comparative effectiveness in preventing dementia remains uncertain.
Objective:
To compare the risk for dementia between SGLT2 inhibitors and dulaglutide (a GLP-1 RA).
Design:
Target trial emulation study.
Setting:
Nationwide health care data of South Korea obtained from the National Health Insurance Service between 2010 and 2022.
Patients:
Patients aged 60 years or older who have T2D and are initiating treatment with SGLT2 inhibitors or dulaglutide.
Measurements:
The primary outcome was the presumed clinical onset of dementia. The date of onset was defined as the year before the date of dementia diagnosis, assuming that the time between the onset of dementia and diagnosis was 1 year. The 5-year risk ratios and risk differences comparing SGLT2 inhibitors with dulaglutide were estimated in a 1:2 propensity score-matched cohort adjusted for confounders.
Results:
Overall, 12 489 patients initiating SGLT2 inhibitor treatment (51.9% dapagliflozin and 48.1% empagliflozin) and 1075 patients initiating dulaglutide treatment were included. In the matched cohort, over a median follow-up of 4.4 years, the primary outcome event occurred in 69 participants in the SGLT2 inhibitor group and 43 in the dulaglutide group. The estimated risk difference was -0.91 percentage point (95% CI, -2.45 to 0.63 percentage point), and the estimated risk ratio was 0.81 (CI, 0.56 to 1.16).
Limitation:
Residual confounding is possible; there was no adjustment for hemoglobin A1c levels or duration of diabetes; the study is not representative of newer drugs, including more effective GLP-1 RAs; and the onset of dementia was not measured directly.
Conclusion:
Under conventional statistical criteria, a risk for dementia between 2.5 percentage points lower and 0.6 percentage point greater for SGLT2 inhibitors than for dulaglutide was estimated to be highly compatible with the data from this study. However, whether these findings generalize to newer GLP-1 RAs is uncertain. Thus, further studies incorporating newer drugs within these drug classes and better addressing residual confounding are required.
Primary Funding Source:
Ministry of Food and Drug Safety of South Korea.
Insights
Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) showed similar dementia risk in type 2 diabetes patients. Further research is needed for newer GLP-1 RAs.
Area of Science:
- Neuroscience
- Endocrinology
- Geriatrics
Background:
- Type 2 diabetes (T2D) patients may benefit from neuroprotective effects of SGLT2 inhibitors and GLP-1 RAs.
- Comparative dementia prevention effectiveness between these drug classes is not well-established.
Purpose of the Study:
- To compare dementia risk between SGLT2 inhibitors and dulaglutide (a GLP-1 RA) in older T2D patients.
- To evaluate the neuroprotective potential of SGLT2 inhibitors versus a specific GLP-1 RA.
Main Methods:
- A target trial emulation study using nationwide South Korean health data (2010-2022).
- Inclusion of T2D patients aged 60+ initiating SGLT2 inhibitors or dulaglutide.
- 1:2 propensity score-matched cohort analysis comparing presumed dementia onset.
Main Results:
- The study included 12,489 SGLT2 inhibitor users and 1,075 dulaglutide users.
- Over a median follow-up of 4.4 years, dementia occurred in 69 participants in the SGLT2 inhibitor group and 43 in the dulaglutide group.
- Estimated 5-year risk difference was -0.91% (CI: -2.45% to 0.63%) and risk ratio was 0.81 (CI: 0.56 to 1.16).
Conclusions:
- SGLT2 inhibitors and dulaglutide demonstrated comparable dementia risk in T2D patients.
- Findings may not generalize to newer, more effective GLP-1 RAs.
- Further studies are required to assess newer agents and address residual confounding.
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