Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

A Novel Mobile App-based Neuromuscular Electrical Stimulation Therapy For Improvement Of Knee Pain, Stiffness, And Function In Knee Osteoarthritis: A Randomized Trial

Background: Knee osteoarthritis (OA) is a widespread and debilitating disease that continues to plague patients. Over the past decade, neuromuscular electrical stimulation (NMES) therapy has shown promise in alleviating knee OA-related symptoms. This study sought to evaluate the efficacy and safety of a home-based NMES therapy for reduction of pain, stiffness, and function associated with knee OA. Material and methods: A randomized, sham-controlled, double-blind, multicenter trial was conducted with 12-week follow-up in 156 knee OA patients receiving either home-based NMES therapy or a modified low-voltage NMES therapy. Outcome measures including knee pain, stiffness, and functionality were collected at baseline through week 12 after the therapy. The primary endpoint was the percentage change from baseline (PCFB) in the Visual Analog Scale (VAS) pain for a patient-nominated physical activity. Secondary endpoints included VAS for general knee pain, Western Ontario and McMaster Universities Osteoarthritis Index, Knee Injury and Osteoarthritis Outcome Score Joint Replacement, and isometric quadriceps strength test. Results: A clinically meaningful reduction for VAS Nominated Activity was higher in the per-protocol treatment-compliant NMES group than that in the sham low-voltage NMES group at week 12 (PCFB of 42.8% vs 38.6%, P = .562). This was similarly true for the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale (PCFBs of 36.8% vs 26.6%, P = .038). Similar trends and reductions of pain were observed for VAS General, Knee Injury and Osteoarthritis Outcome Score Joint Replacement Pain subscale, and isometric quadriceps strength. Conclusion: Home-based NMES treatment resulted in a clinically meaningful reduction of knee pain, stiffness, and knee functional improvements at week 12 compared with sham NMES treatment

Oral Semaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 Trial

OBJECTIVE Efficacy and safety of the glucagon-like peptide 1 (GLP-1) analog oral semaglutide and the sodium–glucose cotransporter 2 inhibitor empagliflozin were compared in patients with type 2 diabetes uncontrolled on metformin. RESEARCH DESIGN AND METHODS Patients were randomized to once-daily open-label treatment with oral semaglutide 14 mg (n = 412) or empagliflozin 25 mg (n = 410) in a 52-week trial. Key end points were change from baseline to week 26 in HbA1c (primary) and body weight (confirmatory secondary). Two estimands addressed efficacy-related questions: treatment policy (regardless of trial product discontinuation or rescue medication) and trial product (on trial product without rescue medication) in all randomized patients. RESULTS Four hundred (97.1%) patients in the oral semaglutide group and 387 (94.4%) in the empagliflozin group completed the trial. Oral semaglutide provided superior reductions in HbA1c versus empagliflozin at week 26 (treatment policy –1.3% vs. –0.9% [–14 vs. –9 mmol/mol], estimated treatment difference [ETD] –0.4% [95% CI –0.6, –0.3] [–5 mmol/mol (–6, –3)]; P &amp;lt; 0.0001). The treatment difference in HbA1c significantly favored oral semaglutide at week 26 for the trial product estimand (–1.4% vs. –0.9% [–15 vs. –9 mmol/mol], ETD –0.5% [95% CI –0.7, –0.4] [–6 mmol/mol (–7, –5)]; P &amp;lt; 0.0001) and at week 52 for both estimands (P &amp;lt; 0.0001). Superior weight loss was not confirmed at week 26 (treatment policy), but oral semaglutide was significantly better than empagliflozin at week 52 (trial product −4.7 vs. −3.8 kg; P = 0.0114). Gastrointestinal adverse events were more common with oral semaglutide. CONCLUSIONS Oral semaglutide was superior to empagliflozin in reducing HbA1c but not body weight at 26 weeks in patients with type 2 diabetes uncontrolled on metformin. At week 52, HbA1c and body weight (trial product estimand) were significantly reduced versus empagliflozin. Oral semaglutide was well tolerated within the established safety profile of GLP-1 receptor agonists. </jats:sec