June 2025 marked a pivotal month for cardiovascular medicine, with the FDA's approval of the first triple combination hypertension pill and breakthrough trial results across multiple therapeutic areas. The regulatory and clinical developments signal significant progress in addressing unmet medical needs in high-risk cardiovascular populations.
FDA Approves Breakthrough Triple Combination Hypertension Therapy
On June 9, 2025, the FDA approved GMRx2 (Widaplik), marking a historic milestone as the first single-pill triple combination therapy approved for initial treatment of hypertension in adults likely needing multiple drugs. The fixed-dose combination contains telmisartan (an angiotensin receptor blocker), amlodipine (a calcium channel blocker), and indapamide (a non-thiazide sulfonamide with an indole ring).
The approval was based on positive results from two Phase 3 trials, GMRx2_ACT and GMRx2_PCT, along with the VERONICA study, which demonstrated statistically significant blood pressure reductions compared to placebo and dual-component comparators. According to George Medicines, the pill's design aligns with global guidelines recommending early use of combination therapy, with a US launch expected in Q4 2025.
The clinical significance is underscored by current treatment gaps: nearly half of American adults have hypertension, yet only about 25% have adequately controlled blood pressure. Available in three dose strengths, including two low-dose options, Widaplik addresses the need for improved control rates through single-pill formulations.
Sotatercept Shows Promise in Early-Stage Pulmonary Arterial Hypertension
Merck announced positive topline results from the Phase 3 HYPERION trial on June 23, 2025, demonstrating that sotatercept-csrk (WINREVAIR) significantly reduced time to clinical worsening in newly diagnosed PAH patients at intermediate or high risk. The randomized, double-blind, placebo-controlled study enrolled 320 participants with functional class II or III symptoms diagnosed within 12 months of study screening.
Based on a composite primary endpoint including all-cause death, non-planned PAH-related hospitalization ≥24 hours, atrial septostomy, lung transplantation, or PAH deterioration, the trial met its goal. Additional benefits were observed in walking distance, NT-proBNP levels, and functional class. At baseline, 72.2% of participants were receiving dual and 27.8% were receiving triple background therapy, with 83.4% not on prostacyclin infusion.
The trial was stopped early following an interim analysis, and Merck announced on July 2, 2025, that the FDA accepted their BLA for label expansion with Priority Review. These findings extend sotatercept's evidence base to earlier-stage patients, building on prior success in advanced PAH.
Semaglutide Demonstrates Vascular Benefits Beyond Glycemic Control
New subanalysis data from the STRIDE trial presented at ADA 2025 on June 21, 2025, showed semaglutide 1.0 mg (Ozempic) significantly improved walking ability, quality of life, and reduced disease progression risk by 54% in patients with type 2 diabetes and peripheral artery disease. The 52-week study of 792 participants demonstrated benefits consistent regardless of HbA1c, diabetes duration, BMI, or SGLT2 inhibitor use.
The analysis reinforced semaglutide's potential vascular benefits beyond glycemic control, with significant improvements in maximum and pain-free walking distances compared to placebo. The findings suggest broader therapeutic applications for GLP-1 receptor agonists in cardiovascular complications of diabetes.
Combination Therapy Shows Superior Kidney Protection
Results from the CONFIDENCE trial presented at ERA 2025 on June 5, 2025, demonstrated that simultaneous initiation of finerenone (Kerendia) and empagliflozin (Jardiance) was well-tolerated and led to a 52% reduction in urinary albumin-to-creatinine ratio (UACR) in patients with chronic kidney disease and type 2 diabetes.
Based on data from 800 patients, combination therapy significantly outperformed either therapy alone, reducing UACR 29% more than finerenone alone and 32% more than empagliflozin alone. According to investigators, this supports early combination use to enhance kidney and cardiovascular protection.
Mixed Results in High-Risk Populations
Not all June developments showed positive outcomes. The ACHIEVE trial presented at ERA 2025 on June 6, 2025, revealed that spironolactone did not significantly reduce cardiovascular death or heart failure hospitalization in dialysis patients. Based on data from over 2,500 participants, the primary outcome occurred in 20.5% of the spironolactone group versus 21.6% in the placebo group (HR 0.92; P = .35).
The findings challenge earlier studies suggesting large cardioprotective benefits, with spironolactone associated with a higher rate of severe hyperkalemia, occurring in 6.6% of patients. These results highlight the complexity of treating cardiovascular risk in dialysis populations.
Lipid Management Advances with Oral PCSK9 Inhibition
The Phase 3 CORALreef trials confirmed the efficacy of enlicitide decanoate, an investigational oral PCSK9 inhibitor, in adults with hyperlipidemia receiving statin therapy. Topline data demonstrated statistically significant and clinically meaningful reductions in LDL-C compared to placebo and compared to ezetimibe, bempedoic acid, and their combination.
Both trials met all primary and key secondary endpoints at Week 24 (CORALreef HeFH) and Week 8 (CORALreef AddOn), with no clinically meaningful difference in adverse events between treatment arms. These findings support enlicitide's potential as the first oral PCSK9-targeted therapy, pending results from the full CORALreef program.
