Trial Files: A Fourth Antidiabetic Drug vs. Metformin Uptitration, Immunomodulatory Agents During Infection in Patients with Rheumatic Disease, and Apixan vs. Rivaroxaban for VTE
How does adding a 4th antidiabetic agent compare to metformin uptitration?
Efficacy and safety of adding a fourth oral antidiabetic drug versus metformin dose escalation in patients with type 2 diabetes inadequately controlled on triple oral combination therapy (EFFORT)
Kim SR et al. Diabetes, Obesity and Metabolism (February 2026)
Bottom Line: This 24-week, randomized, open-label trial evaluated the efficacy and safety of adding a fourth oral antidiabetic drug versus metformin uptitration in adults with type 2 diabetes inadequately controlled (HbA1C 7.0–9.0%) with oral triple therapy (TZD, SGLT2i, DPP-4i). A total of 193 participants were randomized to receive either oral quadruple therapy or metformin uptitration by up to 500mg per day. The primary outcome was the change in HbA1C at week 24, showing a decrease of 0.70% in the quadruple group and 0.40% in the comparator group (p = 0.002). Safety outcomes indicated that adverse events were mild and comparable between groups. The study concluded that oral quadruple therapy is a more effective strategy for glycaemic control without compromising safety.
Is continuing immunomodulatory agents during infection in patients with inflammatory rheumatic disease safe?
Continuation Versus Temporary Interruption of Immunomodulatory Agents During Infections in Patients With Inflammatory Rheumatic Diseases
Opdam MAA et al. Clinical Infectious Diseases (March 2026)
Bottom line: This multi-center, open-label, randomized controlled trial aimed to compare the safety of continuing versus temporarily interrupting immunomodulatory agents in infection-free patients with inflammatory rheumatic diseases. A total of 1142 patients were enrolled and randomized 1:1 to either treatment strategy. The primary outcome was the proportion of patients with serious infections, with 5.15% in the continuation group and 3.73% in the interruption group. The adjusted risk difference was 1.71% (95% CI -1.99 to 5.39), suggesting similar risks associated with both strategies. These findings suggest that temporary interruption and continuation of IA result in similar risk and outcome of infections in IRD patients.
What is the difference in bleeding risk between Apixaban and Rivaroxaban for VTE?
Bleeding Risk with Apixaban vs. Rivaroxaban in Acute Venous Thromboembolism (COBRRA)
Castellucci LA et al. NEJM (March 2026)
Bottom Line: This international, prospective, randomized, open-label, blinded-endpoint trial assigned 2760 patients with acute symptomatic pulmonary embolism or proximal deep vein thrombosis to receive either apixaban or rivaroxaban for 3 months. The apixaban group received 10 mg twice daily for 7 days, followed by 5 mg twice daily, while the rivaroxaban group received 15 mg twice daily for 21 days, followed by 20 mg daily. The primary outcome of clinically relevant bleeding occurred in 3.3% of the apixaban group compared to 7.1% in the rivaroxaban group (relative risk 0.46; P<0.001). Serious adverse events unrelated to bleeding occurred in 2.7% of the apixaban group and 2.2% of the rivaroxaban group, concluding that apixaban significantly reduces bleeding risk compared to rivaroxaban.
Trial Files Issue #2026-05
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