With interest in the dementia prevention effect of Type 2 diabetes medications such as SGLT-2 inhibitors and GLP-1 RAs rising, a study has been published in Korea on the relative prevention effect between the two medications.


On the 3rd, Sungkyunkwan University College of Pharmacy Professor Ju-young Shin’s research team (First author: Bin Hong, coauthor Sungho Bea) announced today that it had published results of a research comparing the dementia prevention effects of SGLT2 inhibitors and dulaglutide in patients with type 2 diabetes using Korea’s healthcare big data.

Dementia is a debilitating neurodegenerative disease characterized by cognitive decline and memory loss. Type 2 diabetes is an important risk factor for dementia, and people with Type 2 diabetes have a significantly increased risk of developing dementia compared with those without.

Given the increasing prevalence of Type 2 diabetes and the burden of dementia, an urgent need exists to find effective strategies to prevent or delay the development of dementia in patients with Type 2 diabetes.

In particular, two classes of diabetes medications, SGLT2 inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), have attracted much attention in recent years due to their excellent effects on cardiovascular and renal function in addition to their blood glucose lowering effects.

Recent studies have also shown that SGLT2 inhibitors and GLP-1 RAs may also have neuroprotective effects.

According to the research team, its research comparing the effects of these two drug classes on cognitive function and dementia risk had limitations, as it was a small, randomized clinical trial with a small sample size of 36 participants and relatively short follow-up periods of 16 weeks.

In addition, patients with a history of psychiatric disorders, which are associated with a higher risk of developing dementia, were excluded, so the results may not accurately reflect the risk of dementia in patients taking this drug in a real-world setting.

Therefore, the effects of SGLT2 inhibitors and GLP-1 RAs on cognitive function and dementia risk in patients with Type 2 diabetes remain unclear.

Using target trial emulation, Professor Shin’s research found that there was no significant difference in the risk of dementia between SGLT2 inhibitors and dulaglutide (the most commonly used GLP-1 RA in Korea) in patients with Type 2 diabetes in the real-world setting.

The research was conducted on patients aged 60 years or older who have type 2 diabetes and are initiating treatment with SGLT2 inhibitors or dulaglutide from May 1, 2016, to December 31, 2020. The final cohort was set by taking into account the patient’s age, gender, diabetes severity, concomitant medications, co-morbidities, medical examination results, and risk factors for dementia based on his or her past year’s medical history to calculate a propensity score.

Within the propensity score-matched cohort, 2,076 patients prescribed SGLT2 inhibitors and 1,038 patients prescribed dulaglutide were included in the research. During a median follow-up of 4.4 years, 69 patients in the SGLT2 inhibitor group and 43 patients in the dulaglutide group developed dementia.

Comparing the SGLT2 inhibitor group to the dulaglutide group, the five-year difference in dementia risk was -0.91 percentage points (95% CI, -2.45 to 0.63 percentage points), with a hazard ratio of 0.81 (CI, 0.56 to 1.16).

“Given the lack of conclusive evidence to support specific drug treatments aimed at preventing dementia in current guidelines, this study is significant in that it generates evidence by directly comparing the risk of dementia for 2 novel diabetes medications - SGLT2 inhibitors and GLP-1 RAs,” said Professor Shin.

“We found no significant difference in the risk of dementia between SGLT2 inhibitors and dulaglutide, but it is uncertain whether these results can be generalized to newer GLP-1 RAs. Thus, further studies incorporating newer drugs within these drug classes and better addressing residual confounding are required,’ the researchers concluded.

The study was conducted by Professor Shin’s research team at Sungkyunkwan University in collaboration with Professor Woo Jung Kim, Department of Psychiatry at Yongin Severance Hospital, and Professor Young Min Cho, Department of Endocrinology at Seoul National University Hospital. The study used customized data from the National Health Insurance Service and was supported by the Ministry of Food and Drug Safety.

The results were published online on August 27 in the Annals of Internal Medicine (IF: 19.6, JCR Ranking 2.3%), a prestigious international journal in the field of medicine.