Comparison on cognitive outcomes of antidiabetic agents for type 2 diabetes: A systematic review and network meta‐analysis

Abstract

We aimed to summarise current evidence on different antidiabetic drugs to delay cognitive impairment, including mild cognitive impairment, dementia, Alzheimer's disease (AD) and vascular dementia, among subjects with type 2 diabetes mellitus (T2DM). Medline, Cochrane and Embase databases were searched from inception to 31 July 2022. Two investigators independently reviewed and screened trials comparing antidiabetic drugs with no antidiabetic drugs, placebo, or other active antidiabetic drugs on cognitive outcomes in T2DM. Data were analysed using meta‐analysis and network meta‐analysis. Twenty‐seven studies met the inclusion criteria, including 3 randomised controlled trials, 19 cohort studies and 5 case‐control studies. Compared with non‐user, SGLT‐2i (OR 0.41 [95% CI 0.22–0.76]), GLP‐1RA (OR 0.34 [95% CI 0.14–0.85]), thiazolidinedione (OR 0.60 [95% CI 0.51–0.69]), and DPP‐4i (OR 0.78 [95% CI 0.61–0.99]) users had a decreased risk of dementia, whereas sulfonylurea (OR 1.43 [95% CI 1.11–1.82]) increased dementia risk. Network meta‐analysis showed that SGLT‐2i was most likely to rank best (SUCRA = 94.4%), GLP‐1 RA second best (SUCRA = 92.7%), thiazolidinedione third best (SUCRA = 74.7%) and DPP‐4i fourth best (SUCRA = 54.9%), while sulfonylurea second worst (SUCRA = 20.0%) for decreasing dementia outcomes, by synthesising evidence from direct and indirect comparisons of multiple intervention. Evidence suggests the effects of SGLT‐2i ≈ GLP‐1 RAs > thiazolidinedione > DPP‐4i for delaying cognitive impairment, dementia and AD outcomes, whereas sulfonylurea was associated with the highest risk. These findings provide evidence for evaluating the optional treatment for clinical practice.PROSPERO RegistrationRegistration no. CRD42022347280.

Clinical Evidence for GLP-1 Receptor Agonists in Alzheimer’s Disease: A Systematic Review

“…Studies have reported an association between GLP-1 RA and improved memory and other cognitive functions in animal models [ 17 ]. Potential cognitive benefits also have been observed in individuals with T2DM, treated with GLP-1 RA [ 18 ]. For example, a post-hoc analysis of an RCT with longitudinal follow-up of more than 4 years observed a potential cognitive benefit associated with a type of GLP-1 RA, dulaglutide, in individuals with T2DM [ 19 ].…”

Glycated Hemoglobin A1c Time in Range and Dementia in Older Adults With Diabetes

“…The study was conducted during a period when newer classes of diabetes medications (eg, sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists) were not frequently prescribed. We were unable to analyze the influence of these specific medications, which may decrease risk of all-cause dementia . We were unable to reliably determine the duration of an individual’s diabetes diagnosis in the electronic health record system.…”

“…We were unable to analyze the influence of these specific medications, which may decrease risk of all-cause dementia. 43 We were unable to reliably determine the duration of an individual’s diabetes diagnosis in the electronic health record system. Finally, our results do not show that prospectively maintaining higher HbA 1c TIR as a treatment strategy will reduce risks for ADRD.…”