An observational study in Inflammatory Arthritis, Diabetes (DM) and Rheumatoid Arthritis (RA), sponsored by Klavs Würgler Hansen. Recruiting at 1 site in Denmark. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-06-25.
Sponsored by Klavs Würgler Hansen · Observational
The purpose of this study is to examine whether the blood test Hemoglobin A1c (HbA1c) gives an accurate picture of blood glucose levels in patients with inflammatory arthritis who are treated with sulfasalazine. HbA1c is widely used to diagnose and monitor diabetes, but sulfasalazine can shorten red blood cell lifespan and thereby lower HbA1c values independently of actual glucose levels.
This may lead to underdiagnosis of diabetes in patients who develop diabetes during sulfasalazine treatment, and to undertreatment in patients with known diabetes due to falsely reassuring HbA1c values.
The study aims to answer two main questions:
HbA1c is widely used to diagnose diabetes and to monitor long-term glycaemic control. HbA1c reflects average blood glucose levels over approximately two months but can be influenced by factors unrelated to glucose, including changes in red blood cell lifespan. Sulfasalazine, a disease-modifying antirheumatic drug commonly used to treat inflammatory arthritis, is known to cause mild haemolysis in some patients, which can lower HbA1c values independently of actual glucose levels.
This effect may have important clinical consequences. In patients without diabetes at the start of sulfasalazine treatment, HbA1c values may remain below diagnostic thresholds even if diabetes develops over time, potentially delaying diagnosis. In patients with established diabetes, sulfasalazine-associated lowering of HbA1c may give a misleading impression of adequate glycaemic control, which may result in insufficient treatment intensification despite elevated true glucose levels. Together, these mechanisms may contribute to underdiagnosis and undertreatment of diabetes in patients receiving sulfasalazine.
CGM provides direct, sensor-based measurements of interstitial glucose levels and is not affected by red blood cell turnover. CGM therefore offers an opportunity to assess actual glycaemic exposure independently of HbA1c. However, prospective data comparing HbA1c with CGM-derived glucose measures in sulfasalazine-treated patients with inflammatory arthritis are lacking.
This study is a prospective observational investigation conducted in patients with inflammatory arthritis treated with sulfasalazine. Participants include both individuals with known diabetes and individuals without known diabetes who have HbA1c values in the borderline range. Each participant undergoes a single study phase in which blinded CGM is worn for up to 14 days, with blood sampling performed within the same time period. In participants without known diabetes, fasting plasma glucose measurements are used to evaluate the presence of previously unrecognised diabetes.
By comparing HbA1c values with CGM-derived average glucose levels, the study aims to evaluate whether HbA1c accurately reflects glycaemic status in sulfasalazine-treated patients. The results are expected to improve understanding of the limitations of HbA1c in this clinical context and to inform future strategies for diabetes diagnosis and monitoring in patients receiving sulfasalazine, including the potential need for alternative or supplementary glucose assessment methods.
Patients will be recruited from the rheumatology outpatient clinic at the Medicial Diagnostic Center, Silkeborg Regional Hospital. Potential participants will be identified electronically using registry data. Scrutiny of their electronical medical records will be performed to confirm eligibility based on the above mentioned inclusion and exclusion criteria.
Exclusion Criteria:
This cohort includes adults with inflammatory arthritis treated with sulfasalazine who do not have a prior diagnosis of diabetes mellitus and have a borderline HbA1c value (≥38 mmol/mol) measured at least two months after initiation of sulfasalazine. Participants undergo blinded continuous glucose monitoring for up to 14 days to assess actual glucose levels. At the end of the monitoring period, blood samples are obtained for fasting plasma glucose and HbA1c. Fasting plasma glucose and HbA1c are used to assess the presence of diabetes mellitus, and thereby whether HbA1c and is suitable for the diagnosis of diabetes in patients treated with sulfasalazine. Comparison of HbA1c with CGM-derived glucose measures allows evaluation of whether HbA1c accurately reflects true glycaemic status in patients treated with sulfasalazine.
This cohort includes adults with inflammatory arthritis and a known diagnosis of diabetes mellitus who are treated with sulfasalazine. Participants undergo blinded continuous glucose monitoring for up to 14 days to assess average glucose levels. HbA1c is measured during the same period. Comparison of HbA1c with CGM-derived glucose measures allows evaluation of whether HbA1c accurately reflects glycaemic control in patients with established diabetes receiving sulfasalazine.
Prevalence of undiagnosed diabetes mellitus
The primary outcome is the prevalence of previously undiagnosed diabetes mellitus among adults with inflammatory arthritis treated with sulfasalazine who do not have a known diagnosis of diabetes and have a borderline HbA1c value. Undiagnosed diabetes is defined based on fasting plasma glucose measurements obtained during the study, in accordance with established diagnostic criteria. The prevalence is expressed as the proportion of participants meeting the diagnostic criteria for diabetes mellitus.
Time frame: Within 14-21 days
Agreement between HbA1c and CGM-derived mean glucose in sulfasalazine-treated patients
The secondary outcome is the agreement between HbA1c and average glucose levels measured by blinded CGM in adults with inflammatory arthritis treated with sulfasalazine. Mean glucose derived from CGM over the monitoring period is compared with contemporaneous HbA1c values to evaluate whether HbA1c accurately reflects true glycaemic status in this population. The analysis includes participants with known diabetes mellitus and participants without known diabetes but with borderline HbA1c values.
Time frame: Within 14-21 days
Feasibility of automated laboratory-based HbA1c alert in sulfasalazine-treated patients
This outcome assesses the feasibility of implementing an automated laboratory-based alert in the laboratory information system (LABKA) to flag potential interpretive limitations of HbA1c in patients treated with sulfasalazine. Feasibility is evaluated by determining whether HbA1c test results can be systematically linked to active sulfasalazine treatment and whether an automated notification can be generated to inform clinicians that HbA1c may underestimate true glycaemic status in this context.
Time frame: Approximately 9 months
Plan to share: Undecided
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Klavs Würgler Hansen