{"id":{"repo_id":"milano","oai_identifier":"oai:air.unimi.it:2434/1119675"},"canonical_url":"https://search.dev.ndltd.org/etd/milano/oai:air.unimi.it:2434/1119675","repository":{"repo_id":"milano","name":"Università degli Studi di Milano","base_url":"https://air.unimi.it/oai/request"},"display":{"title":"THE ROLE OF HYPOGLYCEMIC AGENTS IN AMELIORATING COGNITIVE FUNCTIONS AND PSYCHIATRIC SYMPTOMS: FROM THE PSYCHIATRIC PATIENT TO EVIDENCE-BASED AND PHARMACOEPIDEMIOLOGIC APPROACHES FOR SUPPORTING THE CLINICAL PRACTICE","abstract":"Background: Research highlights a complex link between diabetes-related factors such as insulin resistance, hyperglycemia, and chronic inflammation, all contributing to cognitive decline. Schizophrenia and depression, which often co-occur with type 2 diabetes mellitus, show a bidirectional relationship with diabetes, involving both brain and systemic responses. Antidiabetic drugs such as metformin and drug targeting Glucagon-Like Peptide-1 (GLP-1) are being proposed for psychiatric and cognitive treatments, although their use for non-diabetic purposes remains debated. Methods: The role of antidiabetic drugs in ameliorating psychiatric and cognitive functions was explored across various real-world settings where these drugs are already used for glycemic control. A meta-analysis and meta-regression were conducted to study metformin in schizophrenic patients. Innovative approaches regarding disproportionality analysis of concomitant therapies in pharmacovigilance databases were used to explore all antidiabetic drugs (ATC code: A10) in combination with antidepressants. Survival analysis was performed using Danish healthcare registers to evaluate the potential benefits of GLP-1 analogues (GLP-1a) in older patients. Results: Metformin showed a positive trend without reaching strong statistical significance in ameliorating psychiatric symptoms in a meta-analysis of randomized controlled trials involving schizophrenic patients [SMD (95%CI) = -0.40 (-0.82;0.01), OR (95%CI) = 0.5 (-2.4;3.4)] and reducing the reporting risk of therapy failure in depressive patients [ROR95=1.14, PPR(p)= 1.07 (0.00), EBGM95=0.96 ERAM95=0.89 in FAERS and ROR95=1.48 PPR(p)= 1.34 (0.00) EBGM95=1.22 and ERAM95=0.86 in VigiBase]. GLP-1a and DPP-4 inhibitors (DPP-4i) resulted in better outcomes with a preference for GLP-1a for reducing the risk of major cognitive impairment (dementia) in old diabetic patients [aHR (95% CI) = 1.5 (1.16-2.04), p = 0.003 for DPP-4i compared to GLP1-a (reference group)]. GLP-1a resulted also in a lower reporting rate of therapy failure in depressive patients compared to DPP-4i [ROR95=0.66 vs 0.86 in FAERS and ROR95=0.92 vs 1.06 in VigiBase, respectively]. Conclusions: GLP-1 analogues may offer more substantial clinical benefits. Regarding metformin, there is insufficient evidence of its cognitive benefits. Further research is necessary to confirm these findings and explore their clinical significance.","abstract_html":"Background: Research highlights a complex link between diabetes-related factors such as insulin resistance, hyperglycemia, and chronic inflammation, all contributing to cognitive decline. Schizophrenia and depression, which often co-occur with type 2 diabetes mellitus, show a bidirectional relationship with diabetes, involving both brain and systemic responses. Antidiabetic drugs such as metformin and drug targeting Glucagon-Like Peptide-1 (GLP-1) are being proposed for psychiatric and cognitive treatments, although their use for non-diabetic purposes remains debated. Methods: The role of antidiabetic drugs in ameliorating psychiatric and cognitive functions was explored across various real-world settings where these drugs are already used for glycemic control. A meta-analysis and meta-regression were conducted to study metformin in schizophrenic patients. Innovative approaches regarding disproportionality analysis of concomitant therapies in pharmacovigilance databases were used to explore all antidiabetic drugs (ATC code: A10) in combination with antidepressants. Survival analysis was performed using Danish healthcare registers to evaluate the potential benefits of GLP-1 analogues (GLP-1a) in older patients. Results: Metformin showed a positive trend without reaching strong statistical significance in ameliorating psychiatric symptoms in a meta-analysis of randomized controlled trials involving schizophrenic patients [SMD (95%CI) = -0.40 (-0.82;0.01), OR (95%CI) = 0.5 (-2.4;3.4)] and reducing the reporting risk of therapy failure in depressive patients [ROR95=1.14, PPR(p)= 1.07 (0.00), EBGM95=0.96 ERAM95=0.89 in FAERS and ROR95=1.48 PPR(p)= 1.34 (0.00) EBGM95=1.22 and ERAM95=0.86 in VigiBase]. GLP-1a and DPP-4 inhibitors (DPP-4i) resulted in better outcomes with a preference for GLP-1a for reducing the risk of major cognitive impairment (dementia) in old diabetic patients [aHR (95% CI) = 1.5 (1.16-2.04), p = 0.003 for DPP-4i compared to GLP1-a (reference group)]. GLP-1a resulted also in a lower reporting rate of therapy failure in depressive patients compared to DPP-4i [ROR95=0.66 vs 0.86 in FAERS and ROR95=0.92 vs 1.06 in VigiBase, respectively]. Conclusions: GLP-1 analogues may offer more substantial clinical benefits. Regarding metformin, there is insufficient evidence of its cognitive benefits. Further research is necessary to confirm these findings and explore their clinical significance.","abstract_has_math":false,"creators":["BATTINI, VERA"],"institution":"Università degli Studi di Milano","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["tutor: E. Clementi ; co-tutor: C. Carnovale ; coordinatore: G. Norata","V. Battini","CLEMENTI, EMILIO GIUSEPPE IGNAZIO","CARNOVALE, CARLA","NORATA, GIUSEPPE DANILO"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024-12-19","date_published":"2024-12-19","updated_at":"2026-07-27T20:18:48Z","subjects":["glucose-lowering agent","cognitive disfunction","drug repurposing","Settore BIOS-11/A - Farmacologia"],"languages":["eng"],"rights":["info:eu-repo/semantics/openAccess"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2434/1119675","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["tutor: E. Clementi ; co-tutor: C. Carnovale ; coordinatore: G. Norata","V. Battini","CLEMENTI, EMILIO GIUSEPPE IGNAZIO","CARNOVALE, CARLA","NORATA, GIUSEPPE DANILO"]},{"key":"dc:creator","label":"Author","values":["BATTINI, VERA"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2024-12-19"]},{"key":"dc:publisher","label":"Institution","values":["Università degli Studi di Milano","place:97"]},{"key":"dc:type","label":"Dc Type","values":["info:eu-repo/semantics/doctoralThesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["glucose-lowering agent","cognitive disfunction","drug repurposing","Settore BIOS-11/A - Farmacologia"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["info:eu-repo/semantics/openAccess"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2434/1119675"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Background: Research highlights a complex link between diabetes-related factors such as insulin resistance, hyperglycemia, and chronic inflammation, all contributing to cognitive decline. Schizophrenia and depression, which often co-occur with type 2 diabetes mellitus, show a bidirectional relationship with diabetes, involving both brain and systemic responses. Antidiabetic drugs such as metformin and drug targeting Glucagon-Like Peptide-1 (GLP-1) are being proposed for psychiatric and cognitive treatments, although their use for non-diabetic purposes remains debated. Methods: The role of antidiabetic drugs in ameliorating psychiatric and cognitive functions was explored across various real-world settings where these drugs are already used for glycemic control. A meta-analysis and meta-regression were conducted to study metformin in schizophrenic patients. Innovative approaches regarding disproportionality analysis of concomitant therapies in pharmacovigilance databases were used to explore all antidiabetic drugs (ATC code: A10) in combination with antidepressants. Survival analysis was performed using Danish healthcare registers to evaluate the potential benefits of GLP-1 analogues (GLP-1a) in older patients. Results: Metformin showed a positive trend without reaching strong statistical significance in ameliorating psychiatric symptoms in a meta-analysis of randomized controlled trials involving schizophrenic patients [SMD (95%CI) = -0.40 (-0.82;0.01), OR (95%CI) = 0.5 (-2.4;3.4)] and reducing the reporting risk of therapy failure in depressive patients [ROR95=1.14, PPR(p)= 1.07 (0.00), EBGM95=0.96 ERAM95=0.89 in FAERS and ROR95=1.48 PPR(p)= 1.34 (0.00) EBGM95=1.22 and ERAM95=0.86 in VigiBase]. GLP-1a and DPP-4 inhibitors (DPP-4i) resulted in better outcomes with a preference for GLP-1a for reducing the risk of major cognitive impairment (dementia) in old diabetic patients [aHR (95% CI) = 1.5 (1.16-2.04), p = 0.003 for DPP-4i compared to GLP1-a (reference group)]. GLP-1a resulted also in a lower reporting rate of therapy failure in depressive patients compared to DPP-4i [ROR95=0.66 vs 0.86 in FAERS and ROR95=0.92 vs 1.06 in VigiBase, respectively]. Conclusions: GLP-1 analogues may offer more substantial clinical benefits. Regarding metformin, there is insufficient evidence of its cognitive benefits. Further research is necessary to confirm these findings and explore their clinical significance."]},{"key":"dc:title","label":"Title","values":["THE ROLE OF HYPOGLYCEMIC AGENTS IN AMELIORATING COGNITIVE FUNCTIONS AND PSYCHIATRIC SYMPTOMS: FROM THE PSYCHIATRIC PATIENT TO EVIDENCE-BASED AND PHARMACOEPIDEMIOLOGIC APPROACHES FOR SUPPORTING THE CLINICAL PRACTICE"]}]}],"canonical_facts":{"dc:contributor":["tutor: E. Clementi ; co-tutor: C. Carnovale ; coordinatore: G. Norata","V. Battini","CLEMENTI, EMILIO GIUSEPPE IGNAZIO","CARNOVALE, CARLA","NORATA, GIUSEPPE DANILO"],"dc:creator":["BATTINI, VERA"],"dc:date":["2024-12-19"],"dc:description":["Background: Research highlights a complex link between diabetes-related factors such as insulin resistance, hyperglycemia, and chronic inflammation, all contributing to cognitive decline. Schizophrenia and depression, which often co-occur with type 2 diabetes mellitus, show a bidirectional relationship with diabetes, involving both brain and systemic responses. Antidiabetic drugs such as metformin and drug targeting Glucagon-Like Peptide-1 (GLP-1) are being proposed for psychiatric and cognitive treatments, although their use for non-diabetic purposes remains debated. Methods: The role of antidiabetic drugs in ameliorating psychiatric and cognitive functions was explored across various real-world settings where these drugs are already used for glycemic control. A meta-analysis and meta-regression were conducted to study metformin in schizophrenic patients. Innovative approaches regarding disproportionality analysis of concomitant therapies in pharmacovigilance databases were used to explore all antidiabetic drugs (ATC code: A10) in combination with antidepressants. Survival analysis was performed using Danish healthcare registers to evaluate the potential benefits of GLP-1 analogues (GLP-1a) in older patients. Results: Metformin showed a positive trend without reaching strong statistical significance in ameliorating psychiatric symptoms in a meta-analysis of randomized controlled trials involving schizophrenic patients [SMD (95%CI) = -0.40 (-0.82;0.01), OR (95%CI) = 0.5 (-2.4;3.4)] and reducing the reporting risk of therapy failure in depressive patients [ROR95=1.14, PPR(p)= 1.07 (0.00), EBGM95=0.96 ERAM95=0.89 in FAERS and ROR95=1.48 PPR(p)= 1.34 (0.00) EBGM95=1.22 and ERAM95=0.86 in VigiBase]. GLP-1a and DPP-4 inhibitors (DPP-4i) resulted in better outcomes with a preference for GLP-1a for reducing the risk of major cognitive impairment (dementia) in old diabetic patients [aHR (95% CI) = 1.5 (1.16-2.04), p = 0.003 for DPP-4i compared to GLP1-a (reference group)]. GLP-1a resulted also in a lower reporting rate of therapy failure in depressive patients compared to DPP-4i [ROR95=0.66 vs 0.86 in FAERS and ROR95=0.92 vs 1.06 in VigiBase, respectively]. Conclusions: GLP-1 analogues may offer more substantial clinical benefits. Regarding metformin, there is insufficient evidence of its cognitive benefits. Further research is necessary to confirm these findings and explore their clinical significance."],"dc:identifier":["https://hdl.handle.net/2434/1119675"],"dc:language":["eng"],"dc:publisher":["Università degli Studi di Milano","place:97"],"dc:rights":["info:eu-repo/semantics/openAccess"],"dc:subject":["glucose-lowering agent","cognitive disfunction","drug repurposing","Settore BIOS-11/A - Farmacologia"],"dc:title":["THE ROLE OF HYPOGLYCEMIC AGENTS IN AMELIORATING COGNITIVE FUNCTIONS AND PSYCHIATRIC SYMPTOMS: FROM THE PSYCHIATRIC PATIENT TO EVIDENCE-BASED AND PHARMACOEPIDEMIOLOGIC APPROACHES FOR SUPPORTING THE CLINICAL PRACTICE"],"dc:type":["info:eu-repo/semantics/doctoralThesis"]},"updated_at":"2026-07-27T20:18:48Z"}