SGLT2 inhibitors tied to similar dementia risk as dulaglutide in type 2 diabetes
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Key takeaways:
- Adults aged 60 years or older had a similar 5-year risk for dementia with SGLT2 inhibitors as with dulaglutide.
- More studies are needed to assess dementia risk with newer GLP-1 receptor agonists.
SGLT2 inhibitors and dulaglutide confer a similar risk for dementia among adults aged 60 years and older with type 2 diabetes, according to findings published in Annals of Internal Medicine.
Researchers used observational data to emulate a trial comparing new-onset dementia diagnoses in the 5 years after initiating an SGLT2 inhibitor vs. dulaglutide (Trulicity, Eli Lilly) in type 2 diabetes. While preclinical studies found SGLT2 inhibitors and GLP-1 receptor agonists may have neuroprotective effects, there have been no comparisons of two classes of medication, they wrote.
“We found little difference in the risk for dementia for SGLT2 inhibitors compared with dulaglutide in our data,” Ju-Young Shin, PhD, assistant professor in the School of Pharmacy at Sungkyunkwan University, South Korea, and colleagues wrote. “However, whether these findings generalize to newer GLP-1 receptor agonists is uncertain. Further studies that incorporate newer drugs in these classes and better address residual confounders, including duration of diabetes and HbA1c levels, are required.”
The researchers analyzed adults aged 60 years and older with type 2 diabetes without a history of dementia who were taking metformin and no other diabetes medication in the 3 months before starting an SGLT2 or dulaglutide. The primary outcome was the onset of dementia. Diagnoses of Alzheimer’s disease and vascular dementia were secondary outcomes. Follow-up continued until dementia onset, death or the end of the study in 2022.
The cohort included 12,489 adults prescribed an SGLT2 inhibitor (mean age, 67 years; 59% men) and 1,075 prescribed dulaglutide (mean age, 67 years; 50% men). Of those using an SGLT2 inhibitor, 51.9% received dapagliflozin (Farxiga, AstraZeneca) and 48.1% were prescribed empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly).
To assess dementia risk, researchers used propensity scores to match 1:2 adults using dulaglutide with those using an SGLT2 inhibitor. After propensity-score matching, 2,076 adults using an SGLT2 and 1,038 using dulaglutide were included in the final analysis.
During a median follow-up of 4.4 years, 69 adults in the SGLT2 inhibitor group and 43 in the dulaglutide group developed dementia. The estimated 5-year risk for dementia was not significantly different between the two groups (estimated risk difference, –0.91 percentage point (95% CI, –2.45 to 0.63; estimated risk ratio, 0.81; 95% CI, 0.56-1.16). The two groups also had a similar 5-year risk for developing Alzheimer’s disease and vascular dementia.
Subgroup analyses stratifying adults by age, sex, insulin use, history of cardiovascular disease and hypertension produced similar results.
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