Validation of Hemoglobin A1c in Patients With Inflammatory Arthritis Treated With Sulfasalazine

NCT07416656 | Not Yet Recruiting

• 1 other identifier: 1-10-72-190-25
• Study Type: observational
• Target: 75
• Locations: 0 countries
• Sites: N/A

Brief Summary

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:

1. 1.How many patients treated with sulfasalazine have undiagnosed diabetes despite having HbA1c values below the diagnostic threshold?
2. 2.Does HbA1c underestimate actual glucose levels when compared with continuous glucose monitoring (CGM) in patients with sulfasalazine-treated inflammatory arthritis, both in those with known diabetes and those that are not diagnosed with diabetes but have borderline HbA1c values (≥ 38 mmol/mol)?

Conditions

Inflammatory Arthritis; Diabetes (DM); Rheumatoid Arthritis (RA); Type 1 Diabetes Mellitus; Type 2 Diabetes (T2DM)

Keywords

Validation of HbA1c; Sulfasalazine; Salazopyrin; Continuous glucose monitoring; CGM; Type 2 Diabetes; Diabetes; Hemoglobin A1c; HbA1c; Type 1 Diabetes; Fasting blood glucose

Outcome Measures

Primary Outcomes (1)

• 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.

  Within 14-21 days

Secondary Outcomes (1)

• Agreement between HbA1c and CGM-derived mean glucose in sulfasalazine-treated patients

  Within 14-21 days

Other Outcomes (1)

• Feasibility of automated laboratory-based HbA1c alert in sulfasalazine-treated patients

  Approximately 9 months

Study Arms (2)

Inflammatory arthritis with borderline HbA1c

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.

Inflammatory arthritis with diabetes

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• Age ≥18 years
• Inflammatory arthritis diagnosis (Reumatoid Arthritis, Reaktive Arthritis, Axial spa, Psoriatic spondylitis, and Juvenil artrit)
• HbA1c ≥38 mmol/mol obtained at least 2 months after sulfasalazine initiation OR a diabetes mellitus diagnosis (Type 1 diabetes mellitus, Type 2 diabetes mellitus, Malnutrition-related diabetes mellitus, Other specified diabetes mellitus (andre specificerede former for diabetes), and Unspecified diabetes mellitus (uspecificeret diabetes))
• Can communicate in Danish
• Informed consent including permission to upload glucose data and study ID to the Libreview Platform.

You may not qualify if:

• Systemic treatment or local injections with glucocorticoids within the previous 2 months or planned within the following 4 weeks
• Clinical conditions interfering with the interpretation of HbA1c expect for sulfasalazine alterations in red cell lifespan (etc. Dapson treatment)
• Allergy towards the adhesive used in the CGM
• Considered ineligible for participating (e.g. patients without decision-making capacity, , malignancy, terminal illness, ect.)

Sponsors & Collaborators

• Klavs Würgler Hansen: lead

Related Publications (11)

• Infante M, Padilla N, Alejandro R, Caprio M, Della-Morte D, Fabbri A, Ricordi C. Diabetes-Modifying Antirheumatic Drugs: The Roles of DMARDs as Glucose-Lowering Agents. Medicina (Kaunas). 2022 Apr 21;58(5):571. doi: 10.3390/medicina58050571.

  PMID: 35629988 RESULT

• Farmacies sales of drugs. eSundhed.dk [Internet]. Available from: https://www.esundhed.dk/Emner/Laegemidler/Apotekernes-salg-af-laegemidler

  RESULT

• Lindhardsen J, Ahlehoff O, Gislason GH, Madsen OR, Olesen JB, Torp-Pedersen C, Hansen PR. The risk of myocardial infarction in rheumatoid arthritis and diabetes mellitus: a Danish nationwide cohort study. Ann Rheum Dis. 2011 Jun;70(6):929-34. doi: 10.1136/ard.2010.143396. Epub 2011 Mar 9.

  PMID: 21389043 RESULT

• Baghdadi LR, Woodman RJ, Shanahan EM, Mangoni AA. The impact of traditional cardiovascular risk factors on cardiovascular outcomes in patients with rheumatoid arthritis: a systematic review and meta-analysis. PLoS One. 2015 Feb 17;10(2):e0117952. doi: 10.1371/journal.pone.0117952. eCollection 2015.

  PMID: 25689371 RESULT

• N'Dow SMS, Donnelly LA, Pearson ER, Rena G. In a cohort of individuals with type 2 diabetes using the drug sulfasalazine, HbA1c lowering is associated with haematological changes. Diabet Med. 2021 Sep;38(9):e14463. doi: 10.1111/dme.14463. Epub 2020 Dec 8.

  PMID: 33236391 RESULT

• Mitchell K, Mukhopadhyay B. Drug-Induced Falsely Low A1C: Report of a Case Series From a Diabetes Clinic. Clin Diabetes. 2018 Jan;36(1):80-84. doi: 10.2337/cd17-0005. No abstract available.

  PMID: 29382985 RESULT

• Tack CJ, Wetzels JF. Decreased HbA1c levels due to sulfonamide-induced hemolysis in two IDDM patients. Diabetes Care. 1996 Jul;19(7):775-6. doi: 10.2337/diacare.19.7.775.

  PMID: 8799639 RESULT

• Danish Society of Rheumatology. Rheumatoid arthritis - national clinical guideline [Internet]. [cited 2025 Aug 20].

  RESULT

• Danish Society of Rheumatology. Sulfasalazine [Internet]. [cited 2025 Aug 20]. Available from: https://danskreumatologi.dk/laegemidler/sulfasalazin/

  RESULT

• Christensen SH HN, Janukonyté J, Vestergaard EM, Samson M.. . Brug af glykeret hæmoglobin-måling i praksis. . Ugeskr Læger.183(V12200902):1-8.

  RESULT

• Pant V. HbA1c Below the Reportable Range. Lab Med. 2022 Mar 7;53(2):e44-e47. doi: 10.1093/labmed/lmab082.

  PMID: 34611711 RESULT

MeSH Terms

Conditions

Arthritis; Diabetes Mellitus; Arthritis, Rheumatoid; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Joint Diseases; Musculoskeletal Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Klavs W Hansen, Clinical Professor

  Medicial Diagnostic Center, Silkeborg Regional Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Katrine B Gørlitz, MD

CONTACT

0045 2421 0787; kagoer@rm.dk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: February 10, 2026
• First Posted: February 18, 2026
• Study Start: February 1, 2026
• Primary Completion: June 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: February 18, 2026

Record last verified: 2026-02