Semaglutide,reduction in glycated haemoglobin and the risk of diabetic retinopathy |
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| Authors: | Tina Vilsbøll MD Stephen C. Bain FRCP Lawrence A. Leiter MD Ildiko Lingvay MD David Matthews DPhil Rafael Simó MD Ida Carøe Helmark MD Nelun Wijayasinghe MD Michael Larsen MD |
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| Affiliation: | 1. Steno Diabetes Center Copenhagen, University of Copenhagen, Gentofte, Denmark;2. School of Medicine, Swansea University, Swansea, UK;3. Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Ontario, Canada;4. University of Texas Southwestern Medical Center, Dallas, Texas;5. Oxford Centre for Diabetes, Endocrinology and Metabolism, and Harris Manchester College, University of Oxford, Oxford, UK;6. Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, Barcelona and CIBERDEM (ISCIII), Madrid, Spain;7. Novo Nordisk, S?borg, Denmark;8. Department of Ophthalmology, Rigshospitalet and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark |
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| Abstract: | Aims To evaluate diabetic retinopathy (DR) data from across the SUSTAIN clinical trial programme. Materials and methods The SUSTAIN clinical trial programme evaluated the efficacy and safety of semaglutide, a glucagon‐like peptide‐1 analogue, for the treatment of type 2 diabetes (T2D). In SUSTAIN 6, a 2‐year, pre‐approval cardiovascular outcomes trial, semaglutide was associated with a significant increase in the risk of DR complications (DRC) vs placebo. DR data from across the SUSTAIN trials were evaluated, and post hoc analyses of the SUSTAIN 6 data were conducted. These included subgroup analyses to identify at‐risk patients and a mediation analysis with initial change in glycated haemoglobin (HbA1c; percentage‐points at week 16) as a covariate, to examine the role of the magnitude of reduction in HbA1c as an intermediate factor affecting risk of DRC. Results There was no imbalance in DR adverse events across the SUSTAIN 1 to 5 and Japanese trials. The majority of the effect with semaglutide vs placebo in SUSTAIN 6 may be attributed to the magnitude and rapidity of HbA1c reduction during the first 16 weeks of treatment in patients who had pre‐existing DR and poor glycaemic control at baseline, and who were treated with insulin. Conclusions Early worsening of DR is a known phenomenon associated with the rapidity and magnitude of improvement in glycaemic control with insulin; the DRC findings in SUSTAIN 6 are consistent with this. Guidance regarding the early worsening of DR is recommended with insulin. Similar recommendations may be appropriate for semaglutide. |
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| Keywords: | antidiabetic drug diabetic retinopathy GLP‐1 analogue |
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