Trial Files: Baxdrostat in Uncontrolled and Resistant HTN, Telitacicept for SLE and Orforglipron in T2DM

Nov 3, 2025

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Do aldosterone synthase inhibitors have a use in resistant hypertension?

Efficacy and Safety of Baxdrostat in Uncontrolled and Resistant Hypertension

The BaxHTN Trial. NEJM (August 2025)

Bottom Line: This phase 3, multinational, double-blind, randomized, placebo-controlled trial evaluated the efficacy of baxdrostat versus placebo in patients with uncontrolled or resistant hypertension over 12 weeks. A total of 796 patients were randomized to receive either baxdrostat (1 mg and 2 mg) or placebo, in addition to background therapy, after a 2-week run-in period. The primary outcome was the change in seated systolic blood pressure, with results showing a reduction of -14.5 mm Hg (1 mg) and -15.7 mm Hg (2 mg) compared to -5.8 mm Hg with placebo ((95% CI, –16.5 to –12.5), (95% CI, –17.6 to –13.7), (95% CI, –7.9 to –3.8) respectively.) Safety outcomes indicated that elevated potassium levels occurred in 2.3% (1 mg baxdrostat) and 3.0% (2 mg baxdrostat) of patients receiving baxdrostat. The study concluded that baxdrostat significantly lowers seated systolic blood pressure compared to placebo.

LINK TO ARTICLE (BaxHTN)


Do the benefits of Telitacicept in SLE outweigh the risks?

A Phase 3 Trial of Telitacicept for Systemic Lupus Erythematosus

The 18C010 Trial. NEJM (October 2025)

Bottom line: This phase 3 trial evaluated the efficacy of telitacicept (160 mg) versus placebo in adults with active systemic lupus erythematosus (SLE) over 52 weeks, with random assignment in a 1:1 ratio. A total of 335 participants were enrolled. The primary outcome was the response on the modified SLE Responder Index 4 (SRI-4) at week 52, with 67.1% in the telitacicept group achieving a response compared to 32.7% in the placebo group (adjusted difference, 34.5 percentage points; 95% confidence interval [CI], 24.3 to 44.7; P<0.001). Safety outcomes revealed a higher incidence of adverse events associated with telitacicept, including upper respiratory infections and reduced serum levels of IgG and IgM. The trial concluded that telitacicept led to a higher clinical response but also increased adverse events.

LINK TO ARTICLE (18C010)


How effective is the oral nonpeptide GLP-1 receptor agonist, orforglipron, in early type 2 diabetes?

Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes

The ACHIEVE-1 Trial. NEJM (June 2025)

Bottom Line: This phase 3, double-blind, placebo-controlled trial evaluated the efficacy and safety of orforglipron, a nonpeptide GLP-1 receptor agonist, in 559 adults with early type 2 diabetes treated with diet and exercise alone. Participants received orforglipron at doses of 3 mg, 12 mg, or 36 mg, or placebo daily for 40 weeks. The primary outcome was the change in glycated hemoglobin levels, with results showing a reduction of -1.24, -1.47, and -1.48 percentage points for the respective doses compared to -0.41 percentage points for placebo (P<0.001). The mean glycated hemoglobin level at baseline was 8.0%, and 6.5 to 6.7% with orforglipron at 40 weeks. Safety outcomes indicated mild-to-moderate gastrointestinal events, with no severe hypoglycemia reported.

LINK TO ROUNDS TABLE

LINK TO ARTICLE (ACHIEVE-1)


Trial Files Issue #2025-23