Semaglutide, reduction in glycated haemoglobin and the risk of diabetic retinopathy

Tina Vilsbøll, Stephen C. Bain, Lawrence A. Leiter, Ildiko Lingvay, David Matthews, Rafael Simó, Ida Carøe Helmark, Nelun Wijayasinghe, Michael Larsen

Research output: Contribution to journalArticlepeer-review

155 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)889-897
Number of pages9
JournalDiabetes, Obesity and Metabolism
Issue number4
StatePublished - Apr 2018


  • GLP-1 analogue
  • antidiabetic drug
  • diabetic retinopathy

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


Dive into the research topics of 'Semaglutide, reduction in glycated haemoglobin and the risk of diabetic retinopathy'. Together they form a unique fingerprint.

Cite this