This study examines how different disease-modifying anti-rheumatic drugs (DMARDs) influence the risk of developing diabetes mellitus (DM) and cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA). RA is a chronic inflammatory condition known to increase systemic inflammation, insulin resistance, and metabolic complications. Inflammatory cytokines such as TNF-α and IL-6 disrupt insulin signaling, making RA patients more prone to diabetes. This research evaluates whether specific RA treatments can lower that risk.

A total of 3250 adult RA patients without pre-existing diabetes were included, using medical records from 2018 to 2024. New-onset diabetes was defined as an HbA1c level ≥7%. Medication data were tracked monthly with drug-specific washout periods. The study controlled for age, gender, BMI, smoking, alcohol use, hypertension, lipid disorders, renal disease, hepatitis infections, and the time-dependent use of steroids or statins.

Over an average follow-up of 9.2 years, 320 patients (9.9%) developed diabetes. Those who developed diabetes were typically older, had higher BMI, exhibited higher CRP levels, had reduced kidney function, and showed more rheumatoid factor positivity. Comorbidities such as hypertension, hyperlipidemia, and hepatitis C significantly increased diabetes risk.

The study found clear differences between drug categories. Compared to methotrexate (MTX) alone, biologic DMARDs, MTX-based combination therapy, and other conventional DMARDs significantly reduced the risk of developing diabetes. Among individual drugs, hydroxychloroquine (HCQ) showed the strongest protective effect, reducing diabetes risk by nearly 50%. Sulfasalazine also lowered risk, while TNF-α inhibitors demonstrated a protective trend. However, other biologics showed no significant benefit, likely due to limited usage or smaller sample size.

Chronic steroid use more than doubled diabetes risk, underscoring the need to limit long-term glucocorticoid therapy in RA patients. The study also evaluated cardiovascular disease outcomes and found that MTX-based combinations—especially triple therapy (MTX + SSZ + HCQ)—were associated with a significantly reduced risk of CVD. This highlights the importance of controlling inflammation not only to manage RA but also to prevent metabolic and cardiovascular complications.

In conclusion, the study demonstrates that optimal DMARD selection can significantly reduce the risk of both diabetes and cardiovascular disease in RA patients. Combination therapies and agents like HCQ and TNF inhibitors provide added metabolic protection, whereas long-term steroid use increases diabetes risk. Early and informed treatment choices may greatly improve long-term health outcomes for patients with rheumatoid arthritis.