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This umbrella review analyzed 11 systematic reviews covering 213,604 participants to evaluate interventions for cognitive impairment in Type 2 diabetes mellitus. SGLT2 inhibitors showed the strongest protective effect against cognitive decline, followed by GLP-1 receptor agonists, while multi-component exercise was the most effective lifestyle intervention. Greater benefits were observed in patients with lower baseline cognition, advanced age, female gender, and longer intervention duration.
Why it matters
These findings provide evidence-based guidance for clinicians to select personalized treatments to prevent or slow cognitive decline in diabetic patients, a growing concern as diabetes prevalence increases globally. The identification of specific patient characteristics associated with better outcomes enables targeted intervention strategies that could improve quality of life for millions of people with Type 2 diabetes.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Background: Type 2 diabetes mellitus (T2DM) is one of the fastest-growing epidemics associated with cognitive impairment and dementia. This reduces quality of life among patients with diabetes. Several trials on the management of cognitive impairment have been conducted, although their effectiveness and mechanisms are still unclear. Aim: To synthesize evidence from systematic reviews and meta-analyses of RCTs examining interventions for cognitive impairment in T2DM, stratified by intervention category, comparator, patient characteristics, mechanisms, and clinical outcomes. Methods: We identified 11 systematic reviews (n = 213,604 participants) reporting the effects of cognitive impairment interventions through a comprehensive literature search. Using random-effects models, a meta-meta-analysis was conducted and heterogeneity assessed using I{superscript 2} statistics. AMSTAR and GRADE were used to assess the quality of reviews. Subgroup analyses were conducted for intervention category, cognitive severity, age, diabetes duration, sex, and follow-up duration. Results: Sodium glucose co-transporter inhibitors showed the strongest cognitive improvement effect (pooled OR = 0.44, 95% CI: 0.35-0.55; SUCRA = 94.5%), followed by GLP-1 receptor agonists (RR/OR = 0.60, 95% CI: 0.50-0.72; SUCRA = 92.1%). Among lifestyle interventions, multi-component exercise was the most effective (SMD = 0.69-1.04). The lower baseline cognition (MMSE < 23) benefited more from GLP-1 receptor agonists (Cohen's d = -3.00, p < 0.001). Advanced age ([≥]60 years) and prolonged intervention time ([≥]24 weeks for medications; [≥]6 months for exercise) were associated with greater effects. Female gender showed greater benefit from GLP-1 receptor agonists (HR = 0.63 vs 0.81 for male gender). Conclusions: SGLT2 inhibitors and GLP-1 receptor agonists have the greatest effect on cognition in T2DM, and multi-component exercise is the most effective lifestyle component. The review therefore recommends individualized selection of interventions based on patient characteristics and baseline cognitive status. This calls for high-quality trials with prolonged follow-up to strengthen the evidence base.