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 journalArticle

51 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)889-897
Number of pages9
JournalDiabetes, Obesity and Metabolism
Volume20
Issue number4
DOIs
StatePublished - Apr 1 2018

Fingerprint

Glycosylated Hemoglobin A
Diabetic Retinopathy
Insulin
Placebos
Clinical Trials
Glucagon-Like Peptide 1
Diabetes Complications
semaglutide
Type 2 Diabetes Mellitus
Safety
Therapeutics

Keywords

  • antidiabetic drug
  • diabetic retinopathy
  • GLP-1 analogue

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Vilsbøll, T., Bain, S. C., Leiter, L. A., Lingvay, I., Matthews, D., Simó, R., ... Larsen, M. (2018). Semaglutide, reduction in glycated haemoglobin and the risk of diabetic retinopathy. Diabetes, Obesity and Metabolism, 20(4), 889-897. https://doi.org/10.1111/dom.13172

Semaglutide, reduction in glycated haemoglobin and the risk of diabetic retinopathy. / Vilsbøll, Tina; Bain, Stephen C.; Leiter, Lawrence A.; Lingvay, Ildiko; Matthews, David; Simó, Rafael; Helmark, Ida Carøe; Wijayasinghe, Nelun; Larsen, Michael.

In: Diabetes, Obesity and Metabolism, Vol. 20, No. 4, 01.04.2018, p. 889-897.

Research output: Contribution to journalArticle

Vilsbøll, T, Bain, SC, Leiter, LA, Lingvay, I, Matthews, D, Simó, R, Helmark, IC, Wijayasinghe, N & Larsen, M 2018, 'Semaglutide, reduction in glycated haemoglobin and the risk of diabetic retinopathy', Diabetes, Obesity and Metabolism, vol. 20, no. 4, pp. 889-897. https://doi.org/10.1111/dom.13172
Vilsbøll, Tina ; Bain, Stephen C. ; Leiter, Lawrence A. ; Lingvay, Ildiko ; Matthews, David ; Simó, Rafael ; Helmark, Ida Carøe ; Wijayasinghe, Nelun ; Larsen, Michael. / Semaglutide, reduction in glycated haemoglobin and the risk of diabetic retinopathy. In: Diabetes, Obesity and Metabolism. 2018 ; Vol. 20, No. 4. pp. 889-897.
@article{b46069fce20e448a9029ba2fd95e3585,
title = "Semaglutide, reduction in glycated haemoglobin and the risk of diabetic retinopathy",
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 = "antidiabetic drug, diabetic retinopathy, GLP-1 analogue",
author = "Tina Vilsb{\o}ll and Bain, {Stephen C.} and Leiter, {Lawrence A.} and Ildiko Lingvay and David Matthews and Rafael Sim{\'o} and Helmark, {Ida Car{\o}e} and Nelun Wijayasinghe and Michael Larsen",
year = "2018",
month = "4",
day = "1",
doi = "10.1111/dom.13172",
language = "English (US)",
volume = "20",
pages = "889--897",
journal = "Diabetes, Obesity and Metabolism",
issn = "1462-8902",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Semaglutide, reduction in glycated haemoglobin and the risk of diabetic retinopathy

AU - Vilsbøll, Tina

AU - Bain, Stephen C.

AU - Leiter, Lawrence A.

AU - Lingvay, Ildiko

AU - Matthews, David

AU - Simó, Rafael

AU - Helmark, Ida Carøe

AU - Wijayasinghe, Nelun

AU - Larsen, Michael

PY - 2018/4/1

Y1 - 2018/4/1

N2 - 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.

AB - 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.

KW - antidiabetic drug

KW - diabetic retinopathy

KW - GLP-1 analogue

UR - http://www.scopus.com/inward/record.url?scp=85041694897&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041694897&partnerID=8YFLogxK

U2 - 10.1111/dom.13172

DO - 10.1111/dom.13172

M3 - Article

C2 - 29178519

AN - SCOPUS:85041694897

VL - 20

SP - 889

EP - 897

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1462-8902

IS - 4

ER -