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Diabetes Obes Metab. 2018 Apr;20(4):889-897. doi: 10.1111/dom.13172. Epub 2018 Jan 8.

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

Author information

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, Søborg, Denmark.
8
Department of Ophthalmology, Rigshospitalet and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

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.

KEYWORDS:

GLP-1 analogue; antidiabetic drug; diabetic retinopathy

PMID:
29178519
PMCID:
PMC5888154
DOI:
10.1111/dom.13172
[Indexed for MEDLINE]
Free PMC Article

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