Similar neuroprotective effects from sodium-glucose cotransporter-2 inhibitors and dulaglutide
1. In this target trial emulation study of older adult patients with type 2 diabetes, those who received sodium-glucose cotransporter-2 inhibitors had a similar incidence of dementia versus those who received dulaglutide.
2. The two groups continued to have virtually no risk difference after adjusting for confounders and diagnosis timing.
Evidence Rating Level: 2 (Good)
Study Rundown: Dementia, a neurodegenerative disorder involving cognitive impairment and memory loss, has become a growing public health concern in light of the aging population. It is thought that those with type 2 diabetes (T2D) are at especially high risk for dementia due to the effects of chronic oxidative stress and deranged insulin signaling on the brain. While both sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been associated with slower cognitive decline, few studies have directly compared the neuroprotective effects of these two classes of drugs. This study found that individuals who received SGLT2 inhibitors had a similar likelihood of receiving a diagnosis of dementia over five years as compared to those who received dulaglutide. This similarity persisted after stratifying by a number of demographic and clinical characteristics including age, sex, insulin use, and history of cardiovascular disease. This study excluded individuals who were receiving antidiabetic drugs other than metformin and sulfonylurea, thus limiting generalizability. Another limitation was the relatively short follow-up period, which may have precluded the appearance of an effect over time. Nonetheless, in a cohort of adults with T2D, there was little difference in dementia risk between SGLT2 inhibitors and dulaglutide.
Click to read the study in AIM
Relevant Reading: Association of sodium-glucose cotransporter 2 inhibitors with time to dementia: A population-based cohort study
In-Depth [retrospective cohort]: This retrospective cohort study was conducted to assess the effectiveness of SGLT2 inhibitors compared to dulaglutide, a GLP-1 RA, in preventing the onset of dementia. Participants were deemed eligible if they were 60 years or older, had a diagnosis of T2D, used metformin without other antidiabetic drugs in the past 3 months, had no use of SGLT2 inhibitors of GLP-1 RAs in the past year, and had no history of dementia. A total of 13,564 patients were enrolled, with 12,489 initiating SGLT2 inhibitors, and 1,075 initiating dulaglutide. Of those who started SGLT2 inhibitors, 6,485 (51.9%) were given dapagliflozin and 6,004 (48.1%) were given empagliflozin. Notably, those who started dulaglutide generally had more severe disease as evidenced by a greater prevalence of diabetes-related complications and higher fasting blood glucose. In the propensity score matched cohort, over a median follow-up time of 4.4 years (IQR, 3.3 to 5.3 years), the primary outcome event occurred in 69 patients and 43 patients in the SGLT2 and dulaglutide groups respectively (5 year risk difference, -0.91 percentage points; 95% CI, -2.45 to 0.63 percentage points). The overall risk ratio for dementia was 0.81 (CI, 0.56 to 1.16), and risk ratios for Alzheimer dementia and vascular dementia were 0.80 (CI, 0.55 to 1.15) and 1.74 (CI, 0.22 to 13.83), respectively. In summary, there was no significant difference in the onset of dementia when comparing SGLT2 inhibitors with dulaglutide in patients with T2D.
Image: PD
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