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Semaglutide, reduction in glycated haemoglobin and the risk of diabetic retinopathy
Author(s) -
Vilsbøll Tina,
Bain Stephen C.,
Leiter Lawrence A.,
Lingvay Ildiko,
Matthews David,
Simó Rafael,
Helmark Ida Carøe,
Wijayasinghe Nelun,
Larsen Michael
Publication year - 2018
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.13172
Subject(s) - semaglutide , medicine , placebo , glycated haemoglobin , diabetic retinopathy , diabetes mellitus , clinical trial , type 2 diabetes , adverse effect , endocrinology , liraglutide , alternative medicine , pathology
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.