Pub Date : 2026-01-26DOI: 10.1016/j.diabres.2026.113119
Jesús Gibran Hernández-Pérez , Omer Abdelgadir , Maryam R. Hussain , Jaime P. Almandoz , Carlos H. Barcenas , Amil Shah , Lindsay G. Cowell , Sarah E. Messiah , David S. Lopez
Aims
Glucagon-like peptide-1 receptor agonists (GLP-1 RA) have demonstrated cardioprotective effects; however, their association with cardiomyopathy remains unclear among patients with cancer and type 2 diabetes mellitus (T2D) treated with chemotherapy, radiation, or immunotherapy. We evaluated whether GLP-1 RA initiation reduces cardiomyopathy risk compared with metformin.
Methods
We conducted a retrospective cohort study using a target trial emulation framework within a large global electronic health record database. Adults aged 18–75 years with cancer and T2D, and prior exposure to chemotherapy, radiation, or immunotherapy were included. Treatment strategies were initiation of GLP-1 RA or metformin between January 2006 and July 2024. The primary outcome was incident cardiomyopathy. A 1:1 propensity score–matched cohort was created, and risk differences (RD) and hazard ratios (HR) were estimated.
Results
Among 10,382 matched patients, cardiomyopathy risk at 18.5 years was lower among GLP-1 RA initiators than metformin initiators (0.31% vs 0.94%; RD − 0.64%, 95% CI − 0.90 to − 0.30; HR 0.43, 95% CI 0.24–0.76). Results were consistent across high-risk subgroups.
Conclusions
GLP-1 RA initiation was associated with a lower risk of cardiomyopathy compared with metformin among patients with cancer and T2D, supporting a potential role for GLP-1 RA in cardio-oncology prevention strategies.
目的：胰高血糖素样肽-1受体激动剂（GLP-1 RA）已被证明具有心脏保护作用；然而，在接受化疗、放疗或免疫治疗的癌症和2型糖尿病（T2D）患者中，它们与心肌病的关系尚不清楚。我们评估GLP-1 RA起始与二甲双胍相比是否能降低心肌病风险。方法：我们在一个大型全球电子健康记录数据库中使用目标试验模拟框架进行了一项回顾性队列研究。年龄在18-75岁的癌症和T2D患者，既往接受过化疗、放疗或免疫治疗。治疗策略为2006年1月至2024年7月间开始GLP-1 RA或二甲双胍。主要结局为偶发心肌病。建立一个1:1倾向评分匹配的队列，并估计风险差异（RD）和风险比（HR）。结果：在10382名匹配的患者中，GLP-1 RA启动者的18.5岁心肌病风险低于二甲双胍启动者（0.31% vs 0.94%; RD - 0.64%, 95% CI - 0.90至- 0.30;HR 0.43, 95% CI 0.24-0.76）。结果在高危亚组中是一致的。结论：在癌症和T2D患者中，与二甲双胍相比，GLP-1 RA的起始与较低的心肌病风险相关，支持GLP-1 RA在心脏肿瘤预防策略中的潜在作用。
{"title":"GLP-1 RA initiation versus metformin and risk of cardiomyopathy in patients with cancer and diabetes treated with chemotherapy, radiation, or immunotherapy: a target trial emulation","authors":"Jesús Gibran Hernández-Pérez , Omer Abdelgadir , Maryam R. Hussain , Jaime P. Almandoz , Carlos H. Barcenas , Amil Shah , Lindsay G. Cowell , Sarah E. Messiah , David S. Lopez","doi":"10.1016/j.diabres.2026.113119","DOIUrl":"10.1016/j.diabres.2026.113119","url":null,"abstract":"<div><h3>Aims</h3><div>Glucagon-like peptide-1 receptor agonists (GLP-1 RA) have demonstrated cardioprotective effects; however, their association with cardiomyopathy remains unclear among patients with cancer and type 2 diabetes mellitus (T2D) treated with chemotherapy, radiation, or immunotherapy. We evaluated whether GLP-1 RA initiation reduces cardiomyopathy risk compared with metformin.</div></div><div><h3>Methods</h3><div>We conducted a retrospective cohort study using a target trial emulation framework within a large global electronic health record database. Adults aged 18–75 years with cancer and T2D, and prior exposure to chemotherapy, radiation, or immunotherapy were included. Treatment strategies were initiation of GLP-1 RA or metformin between January 2006 and July 2024. The primary outcome was incident cardiomyopathy. A 1:1 propensity score–matched cohort was created, and risk differences (RD) and hazard ratios (HR) were estimated.</div></div><div><h3>Results</h3><div>Among 10,382 matched patients, cardiomyopathy risk at 18.5 years was lower among GLP-1 RA initiators than metformin initiators (0.31% vs 0.94%; RD − 0.64%, 95% CI − 0.90 to − 0.30; HR 0.43, 95% CI 0.24–0.76). Results were consistent across high-risk subgroups.</div></div><div><h3>Conclusions</h3><div>GLP-1 RA initiation was associated with a lower risk of cardiomyopathy compared with metformin among patients with cancer and T2D, supporting a potential role for GLP-1 RA in cardio-oncology prevention strategies.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"233 ","pages":"Article 113119"},"PeriodicalIF":7.4,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146104372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-25DOI: 10.1016/j.diabres.2026.113114
Jedidiah I. Morton , Emily D. Williams , Jonathan E. Shaw , Dianna J. Magliano
Background and aims
Our aim was to quantify the relationship of a large range of diabetes complications with socioeconomic disadvantage.
Methods
This study included 621,114 people with type 2 diabetes from the Australian National Diabetes Services Scheme, with follow-up from July 2010 to June 2022. These data were linked to hospital admission and death datasets. The association of socioeconomic disadvantage with cause-specific outcomes (first occurrence of either admission or death) was assessed using Poisson regression, adjusted for age, sex, and year.
Results
Most diabetes-related complications studied were positively associated with increasing socioeconomic disadvantage, with the highest incidence rate ratios per 1-SD increase in socioeconomic disadvantage for admission or death from chronic obstructive pulmonary disease (1.19 (95%CI: 1.18, 1.21)) myocardial infarction (1.12 (1.11, 1.13)), heart failure (1.11 (1.10, 1.12)), cellulitis (1.10 (1.09, 1.12)), and end-stage kidney disease (1.09 (1.07, 1.12)). Foot complications and respiratory diseases showed a positive association with disadvantage, as did cardiovascular and kidney diseases, while most cancers, depression, and dementia did not.
Conclusions
Increasing socioeconomic disadvantage was associated with an increased risk of admission or death from most traditional diabetes-related complications and for respiratory disease. However, the associations with emerging complications of diabetes were weaker, null, or the risk decreased with increasing disadvantage.
{"title":"Quantifying the impact of inequality on traditional and emerging diabetes complications: A registry study of cause-specific hospital admissions and deaths in Australia","authors":"Jedidiah I. Morton , Emily D. Williams , Jonathan E. Shaw , Dianna J. Magliano","doi":"10.1016/j.diabres.2026.113114","DOIUrl":"10.1016/j.diabres.2026.113114","url":null,"abstract":"<div><h3>Background and aims</h3><div>Our aim was to quantify the relationship of a large range of diabetes complications with socioeconomic disadvantage.</div></div><div><h3>Methods</h3><div>This study included 621,114 people with type 2 diabetes from the Australian National Diabetes Services Scheme, with follow-up from July 2010 to June 2022. These data were linked to hospital admission and death datasets. The association of socioeconomic disadvantage with cause-specific outcomes (first occurrence of either admission or death) was assessed using Poisson regression, adjusted for age, sex, and year.</div></div><div><h3>Results</h3><div>Most diabetes-related complications studied were positively associated with increasing socioeconomic disadvantage, with the highest incidence rate ratios per 1-SD increase in socioeconomic disadvantage for admission or death from chronic obstructive pulmonary disease (1.19 (95%CI: 1.18, 1.21)) myocardial infarction (1.12 (1.11, 1.13)), heart failure (1.11 (1.10, 1.12)), cellulitis (1.10 (1.09, 1.12)), and end-stage kidney disease (1.09 (1.07, 1.12)). Foot complications and respiratory diseases showed a positive association with disadvantage, as did cardiovascular and kidney diseases, while most cancers, depression, and dementia did not.</div></div><div><h3>Conclusions</h3><div>Increasing socioeconomic disadvantage was associated with an increased risk of admission or death from most traditional diabetes-related complications and for respiratory disease. However, the associations with emerging complications of diabetes were weaker, null, or the risk decreased with increasing disadvantage.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"233 ","pages":"Article 113114"},"PeriodicalIF":7.4,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146060782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aims: This study examines the incidence of anxiety disorders, depression, self-harm, and suicidality after treatment initiation with antihyperglycemic medications in patients with type 2 diabetes (T2D) who take metformin as first-line treatment.
Methods: A large cohort study was conducted using TriNetX electronic health records andincluded adults (≥18 years) with T2D who used metformin and initiated GLP-1 RAs, SGLT2i, DPP4i, or SU between 1 April 2013 and 31 December 2019.
Results: The final three propensity-matched cohorts were 1) GLP-1 RA vs DPP4i (n = 28,536), 2) GLP-1 RA vs SU (n = 23,486), and 3) GLP-1 RA vs SGLT2i (n = 24,052). In a median follow-up of 5.5 years, GLP-1 RAs were associated with a higher risk of depression compared to SGLT2i (HR 1.19, 95% CI 1.11-1.28), and DPP4i (HR 1.06, 95% CI 1.00-1.13) but not SU. Anxiety disorder risk was also higher for GLP-1 RAs versus SGLT2i (HR 1.09, 95% CI 1.02- 1.16) and DPP4i (HR 1.07, 95% CI 1.02-1.13) but not SU. On the contrary, GLP-1 RAs were associated with a lower risk for suicidal ideation in comparison with SU (HR 0.62, 95% CI 0.44-0.87).
Conclusions: GLP-1 RAs were associated with a higher risk of anxiety disorders and depression, but no difference in suicidality or self-harm in comparison to SGLT2i, DPP4i, and lower suicidality risk compared to SU.
目的：本研究探讨以二甲双胍为一线治疗的2型糖尿病（T2D）患者抗高血糖药物治疗开始后焦虑、抑郁和自杀的发生率。方法：使用TriNetX电子健康记录进行了一项大型队列研究，纳入了2013年4月1日至2019年12月31日期间使用二甲双胍并启动GLP-1 RAs、SGLT2i、DPP4i或SU的T2D成人（≥18 岁）。结果:在100,500名患者中，16,424名患者开始使用GLP-1 RAs， 13,855名SGLT2i， 27,614名DPP4i和42,607名SU。在中位5.5 年的随访中，与SGLT2i （HR 1.19, 95% CI 1.11-1.28）和DPP4i （HR 1.06, 95% CI 1.00-1.13）相比，GLP-1 RAs与更高的抑郁风险相关，但与SU无关。GLP-1 RAs与SGLT2i （HR 1.09, 95% CI 1.02- 1.16）和DPP4i （HR 1.07, 95% CI 1.02-1.13）相比，焦虑症风险也更高。与SU相比，GLP-1 RAs与较低的自杀意念风险相关（HR 0.62, 95% CI 0.44-0.87）。结论：GLP-1 RAs与较高的焦虑和抑郁风险相关，但与SGLT2i、DPP4i相比，自杀和自残风险无差异，与SU相比，自杀风险较低。
{"title":"Association of glucagon-like peptide-1 receptor agonist use with anxiety disorders, depression, self-harm, and suicidality: a large cohort study.","authors":"Filippos Anagnostakis, Michail Kokkorakis, Georgia Anastasiou, Shrihari Nagarajan, Christos S Mantzoros","doi":"10.1016/j.diabres.2026.113104","DOIUrl":"10.1016/j.diabres.2026.113104","url":null,"abstract":"<p><strong>Aims: </strong>This study examines the incidence of anxiety disorders, depression, self-harm, and suicidality after treatment initiation with antihyperglycemic medications in patients with type 2 diabetes (T2D) who take metformin as first-line treatment.</p><p><strong>Methods: </strong>A large cohort study was conducted using TriNetX electronic health records andincluded adults (≥18 years) with T2D who used metformin and initiated GLP-1 RAs, SGLT2i, DPP4i, or SU between 1 April 2013 and 31 December 2019.</p><p><strong>Results: </strong>The final three propensity-matched cohorts were 1) GLP-1 RA vs DPP4i (n = 28,536), 2) GLP-1 RA vs SU (n = 23,486), and 3) GLP-1 RA vs SGLT2i (n = 24,052). In a median follow-up of 5.5 years, GLP-1 RAs were associated with a higher risk of depression compared to SGLT2i (HR 1.19, 95% CI 1.11-1.28), and DPP4i (HR 1.06, 95% CI 1.00-1.13) but not SU. Anxiety disorder risk was also higher for GLP-1 RAs versus SGLT2i (HR 1.09, 95% CI 1.02- 1.16) and DPP4i (HR 1.07, 95% CI 1.02-1.13) but not SU. On the contrary, GLP-1 RAs were associated with a lower risk for suicidal ideation in comparison with SU (HR 0.62, 95% CI 0.44-0.87).</p><p><strong>Conclusions: </strong>GLP-1 RAs were associated with a higher risk of anxiety disorders and depression, but no difference in suicidality or self-harm in comparison to SGLT2i, DPP4i, and lower suicidality risk compared to SU.</p>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":" ","pages":"113104"},"PeriodicalIF":7.4,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146060763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-24DOI: 10.1016/j.diabres.2026.113117
Asma Deeb , Hussain Al Saffar , Nadha Yaqoob , Andrea E. Scaramuzza
Aims
Little data exist on the extent of diabetes technology use in the treatment of diabetes in young people outside high-income, Western countries. Here we explored uptake of diabetes technology in the Middle East, Southeast Asia, and beyond.
Methods
A multinational, cross-sectional survey was distributed via major pediatric endocrine societies to healthcare professionals (HCPs) managing children and adolescents with diabetes. The survey assessed CGM and insulin pump penetrance, challenges to adoption, and perceived solutions.
Results
Based on 196 responses from 27 countries, a profound technology gap was confirmed. Nearly half of HCPs (49.2%) reported CGM use in fewer than 5% of their patients, while insulin pump use was even lower, with 74.1% reporting use in under 5% of their pediatric population. While lack of financial resources was the principal barrier (>95%), HCPs also highlighted critical non-financial needs, including simpler technology (53.3%), maintaining patient motivation (52.3%), and deficits in provider training (47.2%) and structured patient education (46.7%).
Conclusion
The adoption of modern diabetes technology is critically low in these regions, reinforcing the existence of an interregional “technology gap”. Improving outcomes for children and adolescents with type 1 diabetes not only relies on funding to promote equitable access but also support through culturally-adapted education for providers, patients, and their families.
{"title":"Diabetes technology use in the Middle East and Southeast Asia: penetrance, challenges, and unmet needs","authors":"Asma Deeb , Hussain Al Saffar , Nadha Yaqoob , Andrea E. Scaramuzza","doi":"10.1016/j.diabres.2026.113117","DOIUrl":"10.1016/j.diabres.2026.113117","url":null,"abstract":"<div><h3>Aims</h3><div>Little data exist on the extent of diabetes technology use in the treatment of diabetes in young people outside high-income, Western countries. Here we explored uptake of diabetes technology in the Middle East, Southeast Asia, and beyond.</div></div><div><h3>Methods</h3><div>A multinational, cross-sectional survey was distributed via major pediatric endocrine societies to healthcare professionals (HCPs) managing children and adolescents with diabetes. The survey assessed CGM and insulin pump penetrance, challenges to adoption, and perceived solutions.</div></div><div><h3>Results</h3><div>Based on 196 responses from 27 countries, a profound technology gap was confirmed. Nearly half of HCPs (49.2%) reported CGM use in fewer than 5% of their patients, while insulin pump use was even lower, with 74.1% reporting use in under 5% of their pediatric population. While lack of financial resources was the principal barrier (>95%), HCPs also highlighted critical non-financial needs, including simpler technology (53.3%), maintaining patient motivation (52.3%), and deficits in provider training (47.2%) and structured patient education (46.7%).</div></div><div><h3>Conclusion</h3><div>The adoption of modern diabetes technology is critically low in these regions, reinforcing the existence of an interregional “technology gap”. Improving outcomes for children and adolescents with type 1 diabetes not only relies on funding to promote equitable access but also support through culturally-adapted education for providers, patients, and their families.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"233 ","pages":"Article 113117"},"PeriodicalIF":7.4,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146050847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-21DOI: 10.1016/j.diabres.2026.113112
Xiao She , Jie Yang , Bincheng Ren , Xin Yang , Xiaojing Cheng , Tian Tian , Shanshan Liu , Xinrui Zhao , Hui Zhao , Xiaoguang Cui
Background
The associations between blood count-derived inflammatory indices and mortality risk in individuals with diabetes and prediabetes have gained attention, but systematic studies are lacking.
Methods
Data from the National Health and Nutrition Examination Survey (NHANES) were analyzed to investigate various inflammatory indices (such as the SII and NLR) in relation to all-cause mortality, cardiovascular disease (CVD) mortality, and diabetes-specific mortality via the Cox proportional hazards model.
Results
A total of 12,119 participants were included, with an average age of 60 years and approximately 52 % being male. During the follow-up, the overall mortality rate was 25.7 %. All nine inflammatory indices were significantly associated with all-cause mortality and CVD mortality (P < 0.01), and seven indices were correlated with diabetes-specific mortality. Eight indices exhibited significant nonlinear relationships with all-cause mortality, with the exception of the NPR, whereas the SIRI, PLR, NPR, and MPR showed significant nonlinear associations with CVD mortality.
Conclusion
Inflammatory indices such as the SII, SIRI, and NLR are significantly associated with all-cause and CVD mortality among U.S. adults with diabetes and prediabetes, demonstrating index-specific association patterns and threshold characteristics.
{"title":"Associations between inflammatory indices derived from complete blood counts and mortality risk in diabetes and prediabetes patients: A cohort study from NHANES 1999--2018","authors":"Xiao She , Jie Yang , Bincheng Ren , Xin Yang , Xiaojing Cheng , Tian Tian , Shanshan Liu , Xinrui Zhao , Hui Zhao , Xiaoguang Cui","doi":"10.1016/j.diabres.2026.113112","DOIUrl":"10.1016/j.diabres.2026.113112","url":null,"abstract":"<div><h3>Background</h3><div>The associations between blood count-derived inflammatory indices and mortality risk in individuals with diabetes and prediabetes have gained attention, but systematic studies are lacking.</div></div><div><h3>Methods</h3><div>Data from the National Health and Nutrition Examination Survey (NHANES) were analyzed to investigate various inflammatory indices (such as the SII and NLR) in relation to all-cause mortality, cardiovascular disease (CVD) mortality, and diabetes-specific mortality via the Cox proportional hazards model.</div></div><div><h3>Results</h3><div>A total of 12,119 participants were included, with an average age of 60 years and approximately 52 % being male. During the follow-up, the overall mortality rate was 25.7 %. All nine inflammatory indices were significantly associated with all-cause mortality and CVD mortality (P < 0.01), and seven indices were correlated with diabetes-specific mortality. Eight indices exhibited significant nonlinear relationships with all-cause mortality, with the exception of the NPR, whereas the<!--> <!-->SIRI, PLR, NPR, and MPR<!--> <!-->showed significant nonlinear associations with CVD mortality.</div></div><div><h3>Conclusion</h3><div>Inflammatory indices such as the SII, SIRI, and NLR are significantly associated with all-cause and CVD mortality among U.S. adults with diabetes and prediabetes, demonstrating index-specific association patterns and threshold characteristics.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"232 ","pages":"Article 113112"},"PeriodicalIF":7.4,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-21DOI: 10.1016/j.diabres.2026.113109
Siqi Jia , Qingping Zeng , Ping Zhu , Feng Liu
Background
Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are widely used for the management of type 2 diabetes mellitus (T2DM) and heart failure (HF). SGLT-2 inhibitors reduce cardiovascular events in T2DM, but concerns persist about diabetic foot infection (DFI).
Objective
To quantify the association between individual SGLT-2 inhibitors and DFI using real-world pharmacovigilance data.
Methods
The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) reports (2004 Q1–2024 Q2) were screened; 62 098 records listed an SGLT-2 inhibitor as the “primary suspect” drug. DFI was identified via eight Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) plus 324 MedDRA Preferred Terms (PTs). Disproportionality was evaluated by Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Information Component (IC), and Empirical Bayes Geometric Mean (EBGM); only “primary suspect” events were retained.
Results
Among 8 312 293 reports, 565 DFI cases implicated an SGLT-2 inhibitor. Canagliflozin showed the highest signal (ROR 162.84; 95 % CI 134.14–197.68), whereas empagliflozin (ROR 0.56) and dapagliflozin (ROR 2.19) did not reach positive criteria. The class-level ROR was 55.51 (45.18–68.21). Additionally, this study examined the time-dependent association between SGLT-2 inhibitors and DFI. The results indicated a significant increase in the ROR for DFI with increasing duration of exposure: the ROR was 11.25 (95% CI: 8.14–15.56) when the exposure duration was ≤30 days; it escalated to 48.77 (95% CI: 39.88–59.64) when the exposure duration exceeded 365 days. The EBGM analysis further corroborated this time-dependent signal, demonstrating that as the duration of exposure lengthened, the envelope of the EBGM and its 95%CI (EBO5/EB95) progressively intensified.
Conclusions
A strong, agent-specific signal links canagliflozin to DFI. Clinicians should prioritise foot surveillance and consider safer SGLT-2 inhibitor alternatives in high-risk patients.
{"title":"Pharmacovigilance analysis of the association between SGLT-2 inhibitors and diabetic foot infections using the FAERS database: An observational study","authors":"Siqi Jia , Qingping Zeng , Ping Zhu , Feng Liu","doi":"10.1016/j.diabres.2026.113109","DOIUrl":"10.1016/j.diabres.2026.113109","url":null,"abstract":"<div><h3>Background</h3><div>Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are widely used for the management of type 2 diabetes mellitus (T2DM) and heart failure (HF). SGLT-2 inhibitors reduce cardiovascular events in T2DM, but concerns persist about diabetic foot infection (DFI).</div></div><div><h3>Objective</h3><div>To quantify the association between individual SGLT-2 inhibitors and DFI using real-world pharmacovigilance data.</div></div><div><h3>Methods</h3><div>The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) reports (2004 Q1–2024 Q2) were screened; 62 098 records listed an SGLT-2 inhibitor as the “primary suspect” drug. DFI was identified via eight Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) plus 324 MedDRA Preferred Terms (PTs). Disproportionality was evaluated by Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Information Component (IC), and Empirical Bayes Geometric Mean (EBGM); only “primary suspect” events were retained.</div></div><div><h3>Results</h3><div>Among 8 312 293 reports, 565 DFI cases implicated an SGLT-2 inhibitor. Canagliflozin showed the highest signal (ROR 162.84; 95 % CI 134.14–197.68), whereas empagliflozin (ROR 0.56) and dapagliflozin (ROR 2.19) did not reach positive criteria. The class-level ROR was 55.51 (45.18–68.21). Additionally, this study examined the time-dependent association between SGLT-2 inhibitors and DFI. The results indicated a significant increase in the ROR for DFI with increasing duration of exposure: the ROR was 11.25 (95% CI: 8.14–15.56) when the exposure duration was ≤30 days; it escalated to 48.77 (95% CI: 39.88–59.64) when the exposure duration exceeded 365 days. The EBGM analysis further corroborated this time-dependent signal, demonstrating that as the duration of exposure lengthened, the envelope of the EBGM and its 95%CI (EBO5/EB95) progressively intensified.</div></div><div><h3>Conclusions</h3><div>A strong, agent-specific signal links canagliflozin to DFI. Clinicians should prioritise foot surveillance and consider safer SGLT-2 inhibitor alternatives in high-risk patients.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"232 ","pages":"Article 113109"},"PeriodicalIF":7.4,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-20DOI: 10.1016/j.diabres.2026.113113
Valeria Gutierrez de Piñeres , Arantxa Ramirez-Cisneros , Claudia S. Tamayo-Torres , Angeliki M. Angelidi , Marianthi Kavelidou , Konstantinos Stefanakis , Christos S. Mantzoros
Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used to treat obesity and metabolic diseases, yet their early impact on body composition and circulating regulators of muscle and bone remain unclear. This study aimed to assess early effects of liraglutide on total and regional body composition and associated changes in circulating markers of muscle and bone metabolism.
Methods: Twenty adults with obesity received liraglutide 3.0 mg/day or placebo for 35 days in this crossover randomized controlled trial. In this secondary analysis, body composition was assessed by dual-energy X-ray absorptiometry at the end of each phase, while hormones were measured by ELISA at baseline and at each of 6 weekly visits over 5 weeks.
Results: Liraglutide reduced body weight, BMI, and total and regional mass (trunk, hip, and extremities). Absolute fat-free mass was slightly but significantly lower. Absolute lean mass in the trunk and extremities decreased, whereas relative lean mass and fat-free mass percentages remained stable at treatment completion.
Conclusions: Short-term liraglutide treatment reduces total and regional mass without altering relative body composition. Further research is warranted to confirm and clarify the clinical significance of these changes, to further study hormonal changes and identify strategies to preserve muscle mass during weight loss.
{"title":"Effects of liraglutide treatment for 35-days on total and regional fat free, lean, and bone mass, and on the Myostatin–Activin–Follistatin–IGF-1 axes: a secondary analysis of a randomized placebo-controlled crossover study","authors":"Valeria Gutierrez de Piñeres , Arantxa Ramirez-Cisneros , Claudia S. Tamayo-Torres , Angeliki M. Angelidi , Marianthi Kavelidou , Konstantinos Stefanakis , Christos S. Mantzoros","doi":"10.1016/j.diabres.2026.113113","DOIUrl":"10.1016/j.diabres.2026.113113","url":null,"abstract":"<div><div><strong>Background</strong>: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used to treat obesity and metabolic diseases, yet their early impact on body composition and circulating regulators of muscle and bone remain unclear. This study aimed to assess early effects of liraglutide on total and regional body composition and associated changes in circulating markers of muscle and bone metabolism.</div><div><strong>Methods</strong>: Twenty adults with obesity received liraglutide 3.0 mg/day or placebo for 35 days in this crossover randomized controlled trial. In this secondary analysis, body composition was assessed by dual-energy X-ray absorptiometry at the end of each phase, while hormones were measured by ELISA at baseline and at each of 6 weekly visits over 5 weeks.</div><div><strong>Results</strong>: Liraglutide reduced body weight, BMI, and total and regional mass (trunk, hip, and extremities). Absolute fat-free mass was slightly but significantly lower. Absolute lean mass in the trunk and extremities decreased, whereas relative lean mass and fat-free mass percentages remained stable at treatment completion.</div><div><strong>Conclusions:</strong> Short-term liraglutide treatment reduces total and regional mass without altering relative body composition. Further research is warranted to confirm and clarify the clinical significance of these changes, to further study hormonal changes and identify strategies to preserve muscle mass during weight loss.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"233 ","pages":"Article 113113"},"PeriodicalIF":7.4,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-18DOI: 10.1016/j.diabres.2026.113110
Sayali S. Deshpande-Joshi , Sonali S. Wagle-Patki , Madhura K. Deshmukh , Himangi G. Lubree , Hemant S. Damle , Suhas R. Otiv , Sanat B. Phatak , Rucha H. Wagh , Shrreya S. Sudade , K. Meenakumari , Smita N. Dhadge , Rajashree P. Kamat , Sayali G. Wadke , Deepa A. Raut , Dattatray S. Bhat , Souvik Bandyopadhyay , Chittaranjan S. Yajnik
Aim
To examine relative influence of maternal diabetes and obesity on neonatal size and adiposity in lean Indian population.
Methods
We analyzed routine clinical data collected in one diabetes clinic. Using ANCOVA (Analysis of Covariance), we examined the association of maternal diabetes and overweight-obesity with neonatal weight, abdominal circumference, and skinfold thickness.
Results
We included 772 pregnancies with diabetes (61-type 1, 79-type 2, 632-gestational diabetes mellites (GDM)) and 349 with normal glucose tolerance (NGT). Maternal type of diabetes and overweight-obesity were independently associated with larger neonatal size and adiposity, with a stronger influence of diabetes. Mothers with type 1 diabetes had lowest Body Mass Index (BMI) and highest Glycated hemoglobin (HbA1c) however, their neonates had highest weight, abdominal circumferences, and skinfolds. Compared to neonates of NGT mothers, those of type 1 diabetes were 300 g heavier, of type 2 diabetes 174 g, and of GDM by 111 g. Neonates of overweight-obese mothers were 128 g heavier than those of non-overweight mothers. Gestational weight gain (GWG) was not associated. Similar findings were seen for abdominal circumference and skinfolds.
Conclusion
In an Indian clinic, maternal glycaemia had a much stronger effect on neonatal adiposity compared to her overweight-obesity. Adequate control of maternal hyperglycemia will help control neonatal adiposity.
{"title":"Neonatal adiposity is predominantly influenced by maternal hyperglycemia than obesity: Evidence from India","authors":"Sayali S. Deshpande-Joshi , Sonali S. Wagle-Patki , Madhura K. Deshmukh , Himangi G. Lubree , Hemant S. Damle , Suhas R. Otiv , Sanat B. Phatak , Rucha H. Wagh , Shrreya S. Sudade , K. Meenakumari , Smita N. Dhadge , Rajashree P. Kamat , Sayali G. Wadke , Deepa A. Raut , Dattatray S. Bhat , Souvik Bandyopadhyay , Chittaranjan S. Yajnik","doi":"10.1016/j.diabres.2026.113110","DOIUrl":"10.1016/j.diabres.2026.113110","url":null,"abstract":"<div><h3>Aim</h3><div>To examine relative influence of maternal diabetes and obesity on neonatal size and adiposity in lean Indian population.</div></div><div><h3>Methods</h3><div>We analyzed routine clinical data collected in one diabetes clinic. Using ANCOVA (Analysis of Covariance), we examined the association of maternal diabetes and overweight-obesity with neonatal weight, abdominal circumference, and skinfold thickness.</div></div><div><h3>Results</h3><div>We included 772 pregnancies with diabetes (61-type 1, 79-type 2, 632-gestational diabetes mellites (GDM)) and 349 with normal glucose tolerance (NGT). Maternal type of diabetes and overweight-obesity were independently associated with larger neonatal size and adiposity, with a stronger influence of diabetes. Mothers with type 1 diabetes had lowest Body Mass Index (BMI) and highest Glycated hemoglobin (HbA1c) however, their neonates had highest weight, abdominal circumferences, and skinfolds. Compared to neonates of NGT mothers, those of type 1 diabetes were 300 g heavier, of type 2 diabetes 174 g, and of GDM by 111 g. Neonates of overweight-obese mothers were 128 g heavier than those of non-overweight mothers. Gestational weight gain (GWG) was not associated. Similar findings were seen for abdominal circumference and skinfolds.</div></div><div><h3>Conclusion</h3><div>In an Indian clinic, maternal glycaemia had a much stronger effect on neonatal adiposity compared to her overweight-obesity. Adequate control of maternal hyperglycemia will help control neonatal adiposity.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"232 ","pages":"Article 113110"},"PeriodicalIF":7.4,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146009206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-15DOI: 10.1016/j.diabres.2026.113108
Nick S.R. Lan , Jonathan Hiew , Pamela Chen , Mahalia McEvoy , Priyal Shah , Ivana Ferreira , J. Carsten Ritter , Laurens Manning , Bu B. Yeap , P. Gerry Fegan , Girish Dwivedi , Emma J. Hamilton
Aims
Pedal medial arterial calcification (pMAC) is a marker of vascular pathology incidentally detected on foot x-ray. We assessed the association between pMAC and major adverse cardiovascular events (MACE) and mortality in patients with diabetes-related foot ulceration (DFU).
Methods
A retrospective study of adults with DFU was performed. pMAC was assessed at five sites on foot x-ray and graded as no/low, moderate or severe. Incident MACE was defined as hospitalisation for myocardial infarction, heart failure, stroke or transient ischaemic attack.
Results
Of 509 patients, 55.2%, 23.4% and 21.4% had no/low, moderate and severe pMAC, respectively. Median follow-up was 531 days (interquartile range 288–793). pMAC was associated with higher MACE or all-cause mortality (no/low 18.1% versus moderate 26.9% versus severe 42.2%; log-rank p < 0.001) and MACE (no/low 11.4% versus moderate 19.3% versus severe 19.3%; log-rank p = 0.020). In multivariable analysis, pMAC was associated with MACE or all-cause mortality (p = 0.009), but not MACE (p = 0.299). MACE was highest in patients with both pMAC and infected ulcers (25.0%), compared with pMAC only (12.5%), infection only (14.0%) and neither (9.0%) (log-rank p < 0.001), remaining significant after adjustment (p = 0.017).
Conclusions
pMAC is associated with MACE or all-cause mortality in patients with DFU, with infected ulcers heightening the risk of MACE.
{"title":"Medial arterial calcification of the foot arteries is associated with incident cardiovascular events or all-cause mortality in patients with diabetes-related foot ulceration","authors":"Nick S.R. Lan , Jonathan Hiew , Pamela Chen , Mahalia McEvoy , Priyal Shah , Ivana Ferreira , J. Carsten Ritter , Laurens Manning , Bu B. Yeap , P. Gerry Fegan , Girish Dwivedi , Emma J. Hamilton","doi":"10.1016/j.diabres.2026.113108","DOIUrl":"10.1016/j.diabres.2026.113108","url":null,"abstract":"<div><h3>Aims</h3><div>Pedal medial arterial calcification (pMAC) is a marker of vascular pathology incidentally detected on foot x-ray. We assessed the association between pMAC and major adverse cardiovascular events (MACE) and mortality in patients with diabetes-related foot ulceration (DFU).</div></div><div><h3>Methods</h3><div>A retrospective study of adults with DFU was performed. pMAC was assessed at five sites on foot x-ray and graded as no/low, moderate or severe. Incident MACE was defined as hospitalisation for myocardial infarction, heart failure, stroke or transient ischaemic attack.</div></div><div><h3>Results</h3><div>Of 509 patients, 55.2%, 23.4% and 21.4% had no/low, moderate and severe pMAC, respectively. Median follow-up was 531 days (interquartile range 288–793). pMAC was associated with higher MACE or all-cause mortality (no/low 18.1% versus moderate 26.9% versus severe 42.2%; log-rank p < 0.001) and MACE (no/low 11.4% versus moderate 19.3% versus severe 19.3%; log-rank p = 0.020). In multivariable analysis, pMAC was associated with MACE or all-cause mortality (p = 0.009), but not MACE (p = 0.299). MACE was highest in patients with both pMAC and infected ulcers (25.0%), compared with pMAC only (12.5%), infection only (14.0%) and neither (9.0%) (log-rank p < 0.001), remaining significant after adjustment (p = 0.017).</div></div><div><h3>Conclusions</h3><div>pMAC is associated with MACE or all-cause mortality in patients with DFU, with infected ulcers heightening the risk of MACE.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"232 ","pages":"Article 113108"},"PeriodicalIF":7.4,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-14DOI: 10.1016/j.diabres.2026.113083
Alhena Younis, Alex E Henney, David R Riley, Matthew Anson, Sizheng S Zhao, Gema H Ibarburu, Rayaz A Malik, Li Su, Gregory Y H Lip, Daniel J Cuthbertson, Uazman Alam
Aims: Evidence suggests sodium glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists reduce the dementia onset/progression. The dual GLP1/GIP receptor agonist, tirzepatide's effect on dementia outcomes remains unknown. We compared tirzepatide, semaglutide and SGLT2-i head-to-head in relation to incident dementia in type 2 diabetes patients METHODS: Three target trial emulations (TTE) were conducted using real-world data from the TriNetX global federated network: TTE1: tirzepatide vs. SGLT2-i, TTE2: semaglutide vs. SGLT2-i and TTE3: tirzepatide vs. semaglutide. Eligible adults with type 2 diabetes and no baseline dementia were included. Follow-up was two years. First diagnosis of dementia, MACE, and all-cause mortality were analysed using survival analysis after propensity score matching.
Results: After matching, TTE1 included 14,462 patients; TTE2, 57,959; TTE3 12,246. Tirzepatide was associated with lower risk of dementia versus semaglutide (HR 0.69, 95% CI 0.48-0.99, p = 0.04) and SGLT2-i (HR 0.66, 95% CI 0.47-0.93, p = 0.02), and lower mortality (HR 0.72, 95% CI 0.58-0.90, p < 0.01; HR 0.29, 95% CI 0.23-0.37, p < 0.01). Tirzepatide and semaglutide reduced MACE vs SGLT2-i.
Conclusions: Tirzepatide is associated with a lower risk of dementia versus semaglutide and SGLT2-I in type 2 diabetes. Findings are hypothesis generating, requiring confirmation in randomised controlled trials.
目的：有证据表明，钠葡萄糖共转运蛋白2抑制剂和胰高血糖素样肽-1受体激动剂可减少痴呆的发病/进展。作为GLP1/GIP受体双激动剂，替西帕肽对痴呆预后的影响尚不清楚。方法：使用TriNetX全球联合网络的真实数据进行了三个目标试验模拟（TTE）： TTE1：替西肽vs. SGLT2-i, TTE2: semaglutide vs. SGLT2-i， TTE3：替西肽vs. semaglutide。纳入了符合条件的2型糖尿病成人，无基线痴呆。随访时间为两年。采用倾向评分匹配后的生存分析分析首次诊断的痴呆、MACE和全因死亡率。结果：匹配后，TTE1纳入14462例患者；TTE2, 57959;TTE3 12246。与塞马鲁肽和SGLT2-i相比，替泽帕肽的痴呆风险更低（HR 0.69, 95% CI 0.48-0.99, p = 0.04）和SGLT2-i (HR 0.66, 95% CI 0.47-0.93, p = 0.02)，死亡率更低（HR 0.72, 95% CI 0.58-0.90, p ）。结论：在2型糖尿病患者中，替泽帕肽与塞马鲁肽和SGLT2-i相比，痴呆风险更低。研究结果是假设生成的，需要在随机对照试验中得到证实。
{"title":"Target trial emulations for tirzepatide, semaglutide and SGLT2-inhibitors for dementia in patients with type 2 diabetes: Real world evidence from a retrospective cohort study.","authors":"Alhena Younis, Alex E Henney, David R Riley, Matthew Anson, Sizheng S Zhao, Gema H Ibarburu, Rayaz A Malik, Li Su, Gregory Y H Lip, Daniel J Cuthbertson, Uazman Alam","doi":"10.1016/j.diabres.2026.113083","DOIUrl":"https://doi.org/10.1016/j.diabres.2026.113083","url":null,"abstract":"<p><strong>Aims: </strong>Evidence suggests sodium glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists reduce the dementia onset/progression. The dual GLP1/GIP receptor agonist, tirzepatide's effect on dementia outcomes remains unknown. We compared tirzepatide, semaglutide and SGLT2-i head-to-head in relation to incident dementia in type 2 diabetes patients METHODS: Three target trial emulations (TTE) were conducted using real-world data from the TriNetX global federated network: TTE1: tirzepatide vs. SGLT2-i, TTE2: semaglutide vs. SGLT2-i and TTE3: tirzepatide vs. semaglutide. Eligible adults with type 2 diabetes and no baseline dementia were included. Follow-up was two years. First diagnosis of dementia, MACE, and all-cause mortality were analysed using survival analysis after propensity score matching.</p><p><strong>Results: </strong>After matching, TTE1 included 14,462 patients; TTE2, 57,959; TTE3 12,246. Tirzepatide was associated with lower risk of dementia versus semaglutide (HR 0.69, 95% CI 0.48-0.99, p = 0.04) and SGLT2-i (HR 0.66, 95% CI 0.47-0.93, p = 0.02), and lower mortality (HR 0.72, 95% CI 0.58-0.90, p < 0.01; HR 0.29, 95% CI 0.23-0.37, p < 0.01). Tirzepatide and semaglutide reduced MACE vs SGLT2-i.</p><p><strong>Conclusions: </strong>Tirzepatide is associated with a lower risk of dementia versus semaglutide and SGLT2-I in type 2 diabetes. Findings are hypothesis generating, requiring confirmation in randomised controlled trials.</p>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":" ","pages":"113083"},"PeriodicalIF":7.4,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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