Orforglipron Significantly Reduces A1C and Weight in Adults with Early Type 2 Diabetes
Orforglipron is a once-daily, oral small-molecule GLP-1 receptor agonist currently in development for type 2 diabetes and weight management. Unlike injectable GLP-1 medications, orforglipron offers a nonpeptide oral alternative, which may improve treatment accessibility and adherence.
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A phase 3, double-blind, placebo-controlled trial evaluated the efficacy and safety of orforglipron over 40 weeks in 559 adults with early type 2 diabetes. Eligible participants had elevated glycated hemoglobin (A1C) levels of 7.0 to 9.5%, a body mass index (BMI) of at least 23 kg/m2, and were managing their diabetes through diet and exercise alone. Patients were randomized to receive one of three daily doses of orforglipron (3 mg, 12 mg, or 36 mg) or placebo. The primary endpoint was change in A1C from baseline to week 40; a key secondary endpoint was change in body weight.
By week 40, patients receiving orforglipron demonstrated significant improvements in glycemic control at all doses. A1C levels dropped by 1.24 to 1.48 percentage points in the orforglipron groups, compared to a 0.41-point reduction with placebo. Final mean A1C levels were 6.5–6.7% with orforglipron. Weight loss was also greater in orforglipron groups, with dose-dependent reductions ranging from 4.5% to 7.6%, compared to 1.7% with placebo.
The medication was generally well tolerated. The most common side effects were mild-to-moderate gastrointestinal symptoms, such as nausea and diarrhea, typically occurring during dose escalation. Importantly, there were no reported cases of severe hypoglycemia. Discontinuation due to side effects was low (4.4–7.8% with orforglipron vs. 1.4% with placebo).
These findings suggest that orforglipron offers a promising new oral treatment option for patients with early type 2 diabetes, providing clinically meaningful improvements in both blood sugar control and weight. The oral formulation may be especially valuable for patients who prefer not to use injectable therapies. (Rosenstock, J., et al. [2025]. Orforglipron, an oral small-molecule GLP-1 receptor agonist, in early type 2 diabetes. N Engl J Med, (2025). Retrieved July 2025 from https://www.nejm.org/doi/10.1056/NEJMoa2505669
Released: August 2025
Nursing Drug Handbook
© 2025 Wolters Kluwer N.V., its subsidiaries and/or its licensors. All rights reserved.
Long-Acting Weekly Risperidone Shows Equivalent Exposure to Daily Dosing in Schizophrenia
Medication non-adherence is a major barrier to successful long-term management of schizophrenia. While long-acting injectable formulations can help improve adherence, they may not be ideal for all patients. A phase 3 trial evaluated a long-acting oral formulation of risperidone (LYN-005) designed to be taken once weekly. The purpose of the study was to determine whether it delivers comparable drug exposure to daily risperidone in patients with stable schizophrenia or schizoaffective disorder.
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Participants first completed a 7-day run-in period with daily immediate-release risperidone (2 mg or 6 mg). They were then transitioned to five once-weekly doses of LYN-005 (15 mg or 45 mg, respectively), with a supplemental half-dose of daily risperidone during the first week of the switch. The primary outcome was to compare key pharmacokinetic parameters, including minimum (Cmin), maximum (Cmax), and average (Cavg) blood concentrations, between weekly and daily formulations.
Among the 83 enrolled participants, 47 completed the full 5-week study. Pharmacokinetic analysis of 44 participants showed that LYN-005 provided sustained therapeutic levels of risperidone across all doses. The geometric mean ratios at week 5 met all prespecified equivalence criteria, indicating that the weekly formulation achieved similar exposure to daily dosing without unexpected fluctuations in drug levels. Participants remained clinically stable throughout the study period.
Gastrointestinal side effects were the most commonly reported treatment-emergent adverse events, occurring in 66% of those receiving LYN-005. One serious adverse event was reported. No new safety signals were identified.
These findings support the use of LYN-005 as a once-weekly oral option for individuals with schizophrenia or schizoaffective disorder. Nurses should consider this new formulation when helping patients who struggle with daily medication adherence and be prepared to monitor for GI-related side effects. (Citrome, L., et al. [2025]. Long-acting oral weekly risperidone (LYN-005) for schizophrenia in the USA (STARLYNG-1): a multicentre, open-label, non-randomised phase 3 trial. Lancet Psychiatry, 12(7), 504–512. Retrieved July 2025 from https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(25)00135-X/abstract)
Released: August 2025
Nursing Drug Handbook
© 2025 Wolters Kluwer N.V., its subsidiaries and/or its licensors. All rights reserved.
Perioperative Pembrolizumab Improves Survival in Locally Advanced Head and Neck Cancer
Locally advanced head and neck squamous cell carcinoma (HNSCC) carries a high risk of recurrence despite treatment with surgery and adjuvant radiotherapy. The benefit of adding immunotherapy in the perioperative setting has remained uncertain. This phase 3 trial evaluated whether neoadjuvant and adjuvant pembrolizumab, a programmed death receptor-1 (PD-1) inhibitor, could improve outcomes when added to standard care in patients with resectable HNSCC.
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A total of 714 patients were randomized to receive either standard treatment alone, which included surgery followed by radiotherapy (with or without cisplatin) or standard care plus pembrolizumab. Those in the pembrolizumab group received two doses before surgery and fifteen additional doses afterward, administered every 3 weeks. The primary endpoint was 36-month event-free survival (EFS), defined as time to disease progression, recurrence, or death. Outcomes were analyzed sequentially among patients with programmed death ligand 1 (PD-L1) expression scores of CPS ≥10, CPS ≥1, and the overall population.
After a median follow-up of 38.3 months, pembrolizumab significantly improved 3-year EFS across all subgroups. In the CPS ≥10 group, EFS was 59.8% in the pembrolizumab group versus 45.9% with standard care alone. Similar improvements were observed in patients with CPS ≥1 (58.2% vs. 44.9%) and in the overall population (57.6% vs. 46.4%). Surgery was completed in approximately 88% of patients in both groups, indicating that neoadjuvant pembrolizumab did not delay or prevent surgery.
Serious Grade 3 or higher treatment-related adverse events occurred in 44.6% of patients receiving pembrolizumab and 42.9% of those receiving standard care alone. Immune-related adverse events of grade 3 or higher, such as pneumonitis or colitis, occurred in 10% of pembrolizumab-treated patients. Treatment-related deaths were rare (1.1% vs. 0.3%).
These findings support the use of pembrolizumab before and after surgery as a way to improve survival in patients with locally advanced HNSCC. Nurses should monitor for immune-related side effects and educate patients on what to expect during long-term immunotherapy. (Uppaluri, R., et al. [2025]. Neoadjuvant and adjuvant pembrolizumab in locally advanced head and neck cancer. N Engl J Med, 393(1), 37–50. Retrieved July 2025 from https://www.nejm.org/doi/full/10.1056/NEJMoa2415434)
Released: August 2025
Nursing Drug Handbook
© 2025 Wolters Kluwer N.V., its subsidiaries and/or its licensors. All rights reserved.
Upadacitinib Shows Durable Remission in Long-Term Study for Ulcerative Colitis
Upadacitinib, an oral Janus kinase (JAK) inhibitor, has demonstrated efficacy for moderate to severe ulcerative colitis in short-term trials. The ongoing phase 3 U-ACTIVATE long-term extension study evaluates the sustained efficacy and safety of upadacitinib over a planned treatment period of 288 weeks. This interim analysis reports outcomes through three years of cumulative treatment. The study is being conducted at 307 centers across 43 countries.
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Patients who completed the 52-week U-ACHIEVE maintenance study were eligible for entry. Those in clinical remission continued on their maintenance dose, while others were allowed to escalate therapy. Key efficacy outcomes included clinical remission, endoscopic remission, and maintenance of both measures, assessed using the adapted Mayo score. The analysis used an as-observed approach, excluding data after dose changes.
Among patients who continued into the long-term extension, 71% of those receiving upadacitinib 15 mg and 67% of those receiving 30 mg were in clinical remission at week 48. At week 96, remission rates were 76% and 74%, respectively. The majority of patients who entered the extension in clinical remission maintained their response through both timepoints. Similarly, endoscopic remission was observed in 49% (15 mg) and 46% (30 mg) of patients at week 48, and in 47% and 45%, respectively, at week 96. Most individuals who entered in endoscopic remission maintained it.
The safety analysis included 467 patients with over 1,000 patient-years of exposure. Treatment-emergent adverse event rates were similar across doses (238.5 and 233.4 events per 100 patient-years). Serious adverse events occurred at rates of 11.7 and 12.4 per 100 patient-years, respectively. Common adverse events of special interest included hepatic abnormalities, lymphopenia, elevated creatine phosphokinase, serious infections, neutropenia, and herpes zoster. Three deaths were reported.
These interim findings support the long-term use of upadacitinib in patients with ulcerative colitis, demonstrating durable clinical and endoscopic remission with a consistent safety profile. (Panaccione, R., et al. [2025]. Long-term efficacy and safety of upadacitinib in patients with moderately to severely active ulcerative colitis: an interim analysis of the phase 3 U-ACTIVATE long-term extension study. Lancet Gastroenterol Hepatol, 10(6), 507–519. Retrieved July 2025 from https://www.thelancet.com/journals/langas/article/PIIS2468-1253(25)00017-2/fulltext)
Released: August 2025
Nursing Drug Handbook
© 2025 Wolters Kluwer N.V., its subsidiaries and/or its licensors. All rights reserved.