Neuropsychiatric and neurocognitive outcomes of metformin versus insulin therapy in Egyptian patients with type 2 diabetes: focus on NGF and BDNF; a cross-sectional study

Abstract Background Type 2 diabetes mellitus (T2DM) and antidiabetic therapy may influence brain health and mood through neurotrophic and psychological pathways. This study compared the effects of metformin versus insulin on cognitive performance, neurotrophic factors, and mood in Egyptian patients with T2DM. Methods This cross-sectional study included 200 T2DM patients aged ≥ 50 years, divided equally into metformin and insulin-treated groups. Cognitive status was assessed using the Mini-Addenbrooke’s Cognitive Examination (Mini-ACE). Serum brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were measured. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). Multiple linear regressions identified independent predictors of cognition, depression, and anxiety. Results Cognitive impairment was present in 35.5% of participants (16% MCI, 19.5% dementia), with a markedly higher prevalence in the insulin group (61%) than in the metformin group (10%), Metformin-treated patients had higher Mini-ACE scores and elevated serum BDNF and NGF. Mean anxiety and depression scores were statistically higher in the insulin group than in the metformin group, with more insulin-treated patients in the moderate-to-severe categories. Regression confirmed depression was driven by anxiety (β = 0.953, p < 0.001), while anxiety was influenced by depression, lower BDNF, and insulin therapy. Conclusion Due to the cross-sectional design, causality cannot be inferred. However, T2DM was associated with a high prevalence of cognitive and affective symptoms, while metformin use is linked to better cognitive and psychological outcomes, possibly via increased BDNF and NGF levels.