Affiliations 1 German Diabetes Foundation, Munich, Germany 2 Division of Endocrinology and Diabetology, University Obesity Centre Hamburg, University Hospital HamburgEppendorf, Germany 3 German Centre for Diabetes Research (DZD e. V.), Neuherberg, Germany 4 Department of Internal Medicine IV, Diabetology, Endocrinology, Nephrology, University Hospital Tübingen, Germany 5 Department of Internal Medicine I, Marienhospital, Stuttgart, Germany 6 Department of Internal Medicine I, University Hospital Bergmannsheil, Bochum, Germany 7 Department of Internal Medicine I, University Hospital RWTH, Aachen, Germany 8 Diabetes Centre Bochum-Hattingen, St.-Josef-Hospital, Ruhr-University, Bochum, Germany 9 MVZ Metabolic Medicine Leipzig, Leipzig, Germany 10 Department of Internal Medicine – Gastroenterology, Diabetology/Endocrinology and Nutritional Medicine, St. Josefkrankenhaus Heidelberg GmbH, Heidelberg, Germany Bibliography Exp Clin Endocrinol Diabetes DOI 10.1055/a-1624-3449 ISSN 0947-7349 © 2022. Thieme. All rights reserved. Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany
Die Praxisempfehlungen der Deutschen Diabetes Gesellschaft (DDG) zusammen mit der Deutschen Gesellschaft für Innere Medizin (DGIM) lehnen sich eng an die Inhalte der Nationalen VersorgungsLeitlinie (NVL) "Therapie des Typ-2-Diabetes" an. Die in diesen Praxisempfehlungen abgebildeten Inhalte sind zum großen Teil die konsentierten Abschnitte der ganzen Arbeitsgruppe, die für die Erarbeitung der Nationalen VersorgungsLeitlinie verantwortlich war. Umfangreiche Details einschließlich der wissenschaftlichen Belege finden Sie in der Langfassung der NVL (http://www.versorgungsleitlinien.de).
Importance:Heart failure (HF) is a common complication of type 2 diabetes (T2D). Oral semaglutide reduced the risk of major adverse cardiovascular (CV) events (MACE; comprising CV death, nonfatal myocardial infarction, or nonfatal stroke) in people with T2D in the SOUL trial, but the impact on HF outcomes in these participants is unknown. Objective:To evaluate the effect of oral semaglutide on HF events, MACE, and safety among participants with or without HF at baseline. Design, Setting, and Participants:This is a secondary analysis of the double-blind, placebo-controlled, event-driven, phase 3b SOUL randomized clinical trial, which was conducted at 444 centers in 33 countries. Participants were enrolled from June 17, 2019, to March 24, 2021, and had T2D and atherosclerotic CV disease and/or chronic kidney disease, stratified according to the presence or absence of HF history at baseline. Data were analyzed from December 2024 to August 2025. Intervention:Once-daily oral semaglutide or placebo in addition to standard of care. Main Outcomes and Measures:Prespecified composite HF outcome (time to first occurrence of HF hospitalization, urgent HF visit, or CV death). Results:Overall, 9650 participants (median [IQR] age, 66.0 [61.0-72.0] years; 2790 [28.9%] female) were randomized, with a mean (SD) follow-up of 47.5 (10.9) months. Of these participants, 2229 (23.1%) had HF history (991 [10.3%] with preserved ejection fraction, 592 [6.1%] with reduced ejection fraction, and 646 [6.7%] with unknown subtype). For participants with HF at baseline, the hazard ratio (HR) for risk of the composite HF outcome with oral semaglutide vs placebo was 0.78 (95% CI, 0.63-0.96) and was 1.01 (95% CI, 0.84-1.20) in those without HF at baseline (P for interaction = .06). Among participants with HF, the HR was 0.59 (95% CI, 0.39-0.86) in those with preserved ejection fraction and 0.98 (95% CI, 0.70-1.38) in those with reduced ejection fraction. There was no heterogeneity in the risk reduction of MACE with oral semaglutide in participants with HF history (HR, 0.83; 95% CI, 0.68-1.01) or without HF history (HR, 0.86; 95% CI, 0.75-0.98) (P for interaction = .77). Serious adverse event occurrence among participants with HF was similar with oral semaglutide (594 [53.8%]) and placebo (642 [57.1%]). Conclusions and Relevance:In this secondary analysis of the SOUL randomized clinical trial, among individuals with T2D, atherosclerotic CV disease, and/or chronic kidney disease, a reduction of HF events was observed with use of oral semaglutide compared with placebo in those with a history of HF, without increasing the risk of serious adverse events. These data support the potential benefit of oral semaglutide in reducing HF events in people with T2D and HF. Trial Registration:ClinicalTrials.gov Identifier: NCT03914326.
International guidelines define standards of care for type 2 diabetes (T2D), obesity, cardiovascular disease (CVD), metabolic dysfunction-associated steatotic liver disease (MASLD) and chronic kidney disease (CKD). Yet implementation at the national level remains inconsistent, leading to persistent gaps between evidence-based recommendations and real-world practice. Key barriers include linguistic and cultural adaptation, limited communication to clinicians, and siloed regulatory and reimbursement processes. Addressing these challenges requires coordinated strategies, such as concise translations, digital platforms and decision-support tools, integration into medical education, and structured monitoring and evaluation frameworks with feedback and incentives. Equitable and sustainable access further depends on coordination between medical societies, governmental authorities, payers, and patient representatives. Evidence from existing initiatives shows that systematic, context-sensitive approaches can measurably improve care. Building on these lessons, this Commentary recommends priorities for national implementation to ensure that guidelines move more effectively from publication to practice and realise their full potential to improve patient outcomes.
Abstract Background Standard treatment for unresectable stage III non-small cell lung cancer (NSCLC) involves chemoradiation (CRT) followed by PD-L1 targeting immune checkpoint inhibition (IO). Integrating 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT into radiotherapy planning reduces toxicity, improves CRT outcomes, and potentially enhances immunotherapy response. Hypofractionated, accelerated CRT shortens treatment time, improves compliance, and may increase CRT completion rates, qualifying more patients for consolidative IO. Methods/design PACCELIO is a multinational, multicenter, randomized, phase II trial comparing the safety and efficacy of FDG-PET/CT based, volume-reduced, hypofractionated CRT with consolidation durvalumab to standard-volume, conventionally fractionated CRT with consolidation durvalumab in inoperable stage III NSCLC. One hundred and ten patients will be enrolled in Germany, Austria, and Switzerland, randomized 1:1, stratified by age, NSCLC stage, and site. The primary objective is to increase completion of CRT with successful transition to consolidation immunotherapy. Secondary outcomes include locoregional and distant tumor control rates, overall survival, safety, and health-related quality of life (HR-QoL). Exploratory outcomes involve prognostic immunomarkers and PET parameters. The primary endpoint of treatment completion will be analyzed using Fisher's Exact test, with safety and efficacy outcomes analyzed via Kaplan-Meier. Discussion The PACCELIO trial addresses a clinical need in stage III NSCLC by combining FDG-PET/CT based RT volume reduction with hypofractionated accelerated CRT and durvalumab immunotherapy. This approach aims to improve treatment completion, compliance, tumor control, and reduce toxicity. The trial will provide insights into the efficacy and safety of this combined treatment, potentially influencing future standards in stage III NSCLC treatment. Recruitment began in July 2024, with ongoing enrollment. Trial registration Clinicaltrials.gov identifier: NCT06102057 (Date of initial registration: 26th October 2023), https://clinicaltrials.gov/study/NCT06102057 .
