Evidence map›Paper›PMID 40576744›Full record

ArticleInflammopharmacology2025

Neuroinflammation and metabolic dysregulation as predictors of cognitive impairment, depression, and quality of life in type 2 diabetes mellitus patients on SGLT2 inhibitors and sulfonylureas.

Haya Majid, Sajad Ul Islam, Sunil Kohli, Nidhi

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Article in Inflammopharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

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6citing papers in PubMed
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3 · Its place in the literature

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6 citing papers in PubMed.

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5 · Who and what money

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4 authors.

Haya MajidDepartment of Translational and Clinical Research, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, 110062, India.
Sajad Ul IslamDepartment of Medicine, Hamdard Institute of Medical Science and Research, New Delhi, 110062, India.
Sunil KohliDepartment of Medicine, Hamdard Institute of Medical Science and Research, New Delhi, 110062, India.
NidhiDepartment of Translational and Clinical Research, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, 110062, India. nidhiagarwal@jamiahamdard.ac.in.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCognitive impairment, depression, and a lower quality of life (QoL) are among the metabolic and neuropsychiatric consequences linked to type 2 diabetes mellitus (T2DM). The pharmacological management of T2DM often involves sodium-glucose co-transporter 2 inhibitors (SGLT2i) and sulfonylureas (SUs), both of which have been shown to influence metabolic control and inflammation. However, their differential effects on neuroinflammatory markers and neuropsychiatric outcomes remain poorly understood. This study aims to compare the effects of SGLT2i and SUs on key metabolic (mTOR, PI3K, AkT), neuroinflammatory (HMGB1, TLR4, ADAM-10, TNF-α, IL-1β, IL-6), and neuroprotective biomarkers (Klotho) associated with cognitive impairment, depression, and QoL in patients with T2DM.

methodsA case-control study was conducted with 166 participants divided into three groups: healthy controls (n = 55), SGLT2i-treated patients (n = 57), and SUs-treated patients (n = 54). The study assessed anthropometric measurements, biochemical markers, kidney function, serum neuroinflammatory and metabolic biomarkers, cognitive function (MoCA), depression (PHQ-9), and QoL (SF-36) through standard protocols.

resultsBoth SGLT2i and SUs significantly increased neuroinflammatory biomarkers (HMGB1, ADAM-10, TNF-α, IL-1β, IL-6) along with mTOR and Klotho compared to the healthy control group (p < 0.001). However, SGLT2i showed a more favourable reduction in these markers. Cognitive impairment and depression were more pronounced in the SUs group (MoCA: 20.03 ± 2.04, PHQ-9: 8.2 ± 1.67) compared to SGLT2i (MoCA: 22.51 ± 4.2, PHQ-9: 6.5 ± 3.8) (p < 0.001).

conclusionSGLT2i are more effective than SUs in modulating metabolic and neuroinflammatory biomarkers and may offer better neuropsychiatric outcomes, potentially improving overall QoL in T2DM patients. Further research is needed to explore the long-term effects of these drugs on neurodegeneration and cognitive health.

Indexed as

Cognitive DysfunctionDepressionDiabetes Mellitus, Type 2Neuroinflammatory DiseasesSodium-Glucose Transporter 2 InhibitorsSulfonylurea CompoundsAgedBiomarkersCase-Control StudiesFemaleHumansHypoglycemic AgentsInflammationMaleMiddle AgedQuality of LifeBiomarkersHypoglycemic AgentsSodium-Glucose Transporter 2 InhibitorsSulfonylurea CompoundsBiomarkersDiabetesMetabolismSodium-glucose co-transporter 2 inhibitorsSulfonylureas

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.