To evaluate the effect of lobeglitazone on renal disease progression in patients with type 2 diabetes mellitus using longitudinal real-world data.

Retrospective cohort study.

Hospital-based Common Data Model database.

A total of 14 712 adults with type 2 diabetes mellitus who visited the Diabetes Center of Ewha Womans University Mokdong Hospital between 2013 and 2019 were identified. A 1:2 propensity score matching was performed to compare patients treated with lobeglitazone plus metformin with those receiving metformin monotherapy, sulfonylurea plus metformin, or a dipeptidyl peptidase-4 (DPP4) inhibitor plus metformin.

Treatment with lobeglitazone plus metformin compared with metformin monotherapy, sulfonylurea plus metformin or DPP4 inhibitor plus metformin.

Renal progression, defined as initiation of renal replacement therapy, a sustained ≥30% decline in estimated glomerular filtration rate (eGFR) from baseline, or doubling of serum creatinine with a concurrent eGFR ≤45 mL/min/1.73 m².

The HR of renal progression was 0.84 (95% CI 0.58 to 1.21) in the lobeglitazone plus metformin compared with metformin monotherapy, 1.00 (95% CI 0.79 to 1.27) compared with sulfonylurea plus metformin group, 1.10 (95% CI 0.84 to 1.44) compared with DPP4 inhibitor plus metformin group after adjusting for multiple variables. Subgroup analyses demonstrated significant interactions by sex in the comparison with metformin monotherapy (P for interaction=0.0179) and by glycaemic control in the comparisons with sulfonylurea plus metformin (P for interaction=0.0161) and DPP4 inhibitor plus metformin (P for interaction=0.0006), suggesting potential heterogeneity in treatment effects.

Lobeglitazone showed renal outcomes comparable to those of other antidiabetic medications, with a possible heterogeneity in treatment effects according to sex and glycaemic control.

The global burden of chronic immune-mediated inflammatory diseases (IMIDs) is increasing, and rising prevalence rates significantly affect socioeconomic factors and quality of life. Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), along with ankylosing spondylitis (AS), are prominent chronic IMIDs that share overlapping pathophysiological mechanisms. Recent research has highlighted the importance of the gut microbiota in the pathogenesis of these diseases, suggesting that shared microbial dysbiosis may contribute to their development. Comprehensive research focusing on the gut and oral microbial characteristics and environmental factors is essential to elucidate the fundamental pathophysiology and develop personalised management strategies for IBD and AS. In-depth analyses and insights based on multiomics approaches are required to achieve these objectives.

This protocol describes a nationwide prospective observational study of CD, UC and AS in a Korean population. Over 5 years, we aim to recruit at least 900 patients with IBD and 200 first-degree relatives (FDRs), 500 patients with AS and 200 of their FDRs, and 2244 healthy controls. We will systematically collect clinical data and biological samples, including saliva, stool, blood and tissue biopsies, for integrative multiomics analyses focusing primarily on the microbiome. Highly advanced full-length 16S ribosomal RNA gene sequencing and shotgun metagenomics will be used to characterise the microbial composition of saliva and stool samples. Quantitative microbiome profiling will be used to address the pathological, physiological and ecological differences between microbial groups that may be masked by their relative abundance. Metabolomic analyses will be conducted on saliva, stool and plasma samples to assess functional metabolic profiles. Culturomics will be used to isolate, identify and characterise the diversity of microbial species, including rare or previously unrecognised species, to provide a comprehensive understanding of the microbiota associated with these diseases.

Ethical approval was obtained from the Ethics Committee of Kyung Hee University Hospital, Hanyang University Hospital, Kangbuk Samsung Hospital, Yeungnam University Hospital, Kyungpook National University Hospital, Chonnam National University Hospital, Wonkwang University Hospital, Catholic University Daejeon St. Mary’s Hospital, Soon Chun Hyang University Hospital Cheonan, Chung-Ang University Hospital, Inje University Haeundae Paik Hospital, Dankook University Hospital, Hanyang University Guri Hospital, Kyung Hee University Hospital at Gangdong, Chung-Ang University Gwangmyeong Hospital and Keimyung University Dongsan Hospital. Our research team will provide detailed information about the study, including an information sheet explaining its aims and procedures, prior to enrolment. Prospective participants will be informed that they have the right to withdraw from the study at any time, without penalty. Participants will be assured of the anonymity and confidentiality of any data they provide throughout the study, using participant numbers and the storage of sensitive data in locked cabinets. Participants will be enrolled in the study only after providing written informed consent to the research staff. The results of this study will be disseminated to healthcare and academic professionals through publications in peer-reviewed journals and presentations at international conferences.

This prospective observational study is registered at ClinicalTrials.gov ((ID: NCT06124833, data first posted: 9 November 2023); (ID: NCT06076083, data first posted: 21 November 2023) and (ID: NCT06183697, data first posted: 27 December 2023)).