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

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

U2 - 10.1111/dom.13172

DO - 10.1111/dom.13172

M3 - Journal article

AN - SCOPUS:85041694897

SN - 1462-8902

VL - 20

SP - 889

EP - 897

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

IS - 4

ER -