Effects of semaglutide and empagliflozin on oxygenation, vascular autoregulation, and central thickness of the retina in people with type 2 diabetes: A prespecified secondary analysis of a randomised clinical trial

Søren Gullaksen; Liv Vernstrøm; Steffen Skovgaard Sørensen; Kristian Løkke Funck; Line Petersen; Toke Bek; Per Løgstrup Poulsen; Esben Laugesen

doi:10.1016/j.jdiacomp.2023.108472

Effects of semaglutide and empagliflozin on oxygenation, vascular autoregulation, and central thickness of the retina in people with type 2 diabetes: A prespecified secondary analysis of a randomised clinical trial

Søren Gullaksen^*, Liv Vernstrøm, Steffen Skovgaard Sørensen, Kristian Løkke Funck, Line Petersen, Toke Bek, Per Løgstrup Poulsen, Esben Laugesen

^*Corresponding author for this work

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Abstract

AIMS: Semaglutide and empagliflozin have shown cardiovascular protection. In SUSTAIN-6, semaglutide was associated with an increased risk of diabetic retinopathy. We investigated whether changes in retinal oxygenation, retinal vascular autoregulation, and central retinal thickness are altered by semaglutide, empagliflozin or the combination.

METHODS: This study was a prespecified, secondary outcome from a randomised, 32 weeks partly placebo-controlled, partly open-label, clinical trial on the effects of semaglutide and empagliflozin on arterial stiffness and kidney oxygenation. A total of 120 participants with type 2 diabetes, established or high risk of cardiovascular disease and age ≥50 years were randomised into four parallel groups (semaglutide, empagliflozin, the combination or tablet placebo, n = 30 for each group). We primarily hypothesized that semaglutide would increase venular oxygenation.

RESULTS: We found no changes in retinal arteriolar, venular or venular-arteriolar oxygenation nor in retinal vessel diameter regardless of treatment group. Semaglutide increased central retinal thickness compared to placebo with ~1 % (3.8 μm 95 % CI [0.9;6.7], p = 0.009) with no changes in the empagliflozin or combination group.

CONCLUSION: Neither semaglutide, empagliflozin nor the combination alters markers of retinal function. The effect of semaglutide on central retinal thickness was small, but the clinical significance is uncertain.

Original language	English
Article number	108472
Journal	Journal of Diabetes and its Complications
Volume	37
Issue	5
Pages (from-to)	1-7
Number of pages	7
ISSN	1056-8727
DOIs	https://doi.org/10.1016/j.jdiacomp.2023.108472
Publication status	Published - May 2023

Keywords

Diabetic retinopathy
Glucagon-like peptide 1 receptor agonist
Oximetry
Sodium-glucose transporter 2 inhibitors

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Gullaksen, S., Vernstrøm, L., Sørensen, S. S., Funck, K. L., Petersen, L., Bek, T., Poulsen, P. L., & Laugesen, E. (2023). Effects of semaglutide and empagliflozin on oxygenation, vascular autoregulation, and central thickness of the retina in people with type 2 diabetes: A prespecified secondary analysis of a randomised clinical trial. Journal of Diabetes and its Complications, 37(5), 1-7. Article 108472. https://doi.org/10.1016/j.jdiacomp.2023.108472

Gullaksen, Søren ; Vernstrøm, Liv ; Sørensen, Steffen Skovgaard et al. / Effects of semaglutide and empagliflozin on oxygenation, vascular autoregulation, and central thickness of the retina in people with type 2 diabetes : A prespecified secondary analysis of a randomised clinical trial. In: Journal of Diabetes and its Complications. 2023 ; Vol. 37, No. 5. pp. 1-7.

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title = "Effects of semaglutide and empagliflozin on oxygenation, vascular autoregulation, and central thickness of the retina in people with type 2 diabetes: A prespecified secondary analysis of a randomised clinical trial",

abstract = "AIMS: Semaglutide and empagliflozin have shown cardiovascular protection. In SUSTAIN-6, semaglutide was associated with an increased risk of diabetic retinopathy. We investigated whether changes in retinal oxygenation, retinal vascular autoregulation, and central retinal thickness are altered by semaglutide, empagliflozin or the combination.METHODS: This study was a prespecified, secondary outcome from a randomised, 32 weeks partly placebo-controlled, partly open-label, clinical trial on the effects of semaglutide and empagliflozin on arterial stiffness and kidney oxygenation. A total of 120 participants with type 2 diabetes, established or high risk of cardiovascular disease and age ≥50 years were randomised into four parallel groups (semaglutide, empagliflozin, the combination or tablet placebo, n = 30 for each group). We primarily hypothesized that semaglutide would increase venular oxygenation.RESULTS: We found no changes in retinal arteriolar, venular or venular-arteriolar oxygenation nor in retinal vessel diameter regardless of treatment group. Semaglutide increased central retinal thickness compared to placebo with ~1 % (3.8 μm 95 % CI [0.9;6.7], p = 0.009) with no changes in the empagliflozin or combination group.CONCLUSION: Neither semaglutide, empagliflozin nor the combination alters markers of retinal function. The effect of semaglutide on central retinal thickness was small, but the clinical significance is uncertain.",

keywords = "Diabetic retinopathy, Glucagon-like peptide 1 receptor agonist, Oximetry, Sodium-glucose transporter 2 inhibitors",

author = "S{\o}ren Gullaksen and Liv Vernstr{\o}m and S{\o}rensen, {Steffen Skovgaard} and Funck, {Kristian L{\o}kke} and Line Petersen and Toke Bek and Poulsen, {Per L{\o}gstrup} and Esben Laugesen",

year = "2023",

month = may,

doi = "10.1016/j.jdiacomp.2023.108472",

language = "English",

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Gullaksen, S , Vernstrøm, L, Sørensen, SS, Funck, KL , Petersen, L , Bek, T , Poulsen, PL & Laugesen, E 2023, 'Effects of semaglutide and empagliflozin on oxygenation, vascular autoregulation, and central thickness of the retina in people with type 2 diabetes: A prespecified secondary analysis of a randomised clinical trial', Journal of Diabetes and its Complications, vol. 37, no. 5, 108472, pp. 1-7. https://doi.org/10.1016/j.jdiacomp.2023.108472

Effects of semaglutide and empagliflozin on oxygenation, vascular autoregulation, and central thickness of the retina in people with type 2 diabetes: A prespecified secondary analysis of a randomised clinical trial. / Gullaksen, Søren ; Vernstrøm, Liv; Sørensen, Steffen Skovgaard et al.
In: Journal of Diabetes and its Complications, Vol. 37, No. 5, 108472, 05.2023, p. 1-7.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Effects of semaglutide and empagliflozin on oxygenation, vascular autoregulation, and central thickness of the retina in people with type 2 diabetes

T2 - A prespecified secondary analysis of a randomised clinical trial

AU - Gullaksen, Søren

AU - Vernstrøm, Liv

AU - Sørensen, Steffen Skovgaard

AU - Funck, Kristian Løkke

AU - Petersen, Line

AU - Bek, Toke

AU - Poulsen, Per Løgstrup

AU - Laugesen, Esben

PY - 2023/5

Y1 - 2023/5

N2 - AIMS: Semaglutide and empagliflozin have shown cardiovascular protection. In SUSTAIN-6, semaglutide was associated with an increased risk of diabetic retinopathy. We investigated whether changes in retinal oxygenation, retinal vascular autoregulation, and central retinal thickness are altered by semaglutide, empagliflozin or the combination.METHODS: This study was a prespecified, secondary outcome from a randomised, 32 weeks partly placebo-controlled, partly open-label, clinical trial on the effects of semaglutide and empagliflozin on arterial stiffness and kidney oxygenation. A total of 120 participants with type 2 diabetes, established or high risk of cardiovascular disease and age ≥50 years were randomised into four parallel groups (semaglutide, empagliflozin, the combination or tablet placebo, n = 30 for each group). We primarily hypothesized that semaglutide would increase venular oxygenation.RESULTS: We found no changes in retinal arteriolar, venular or venular-arteriolar oxygenation nor in retinal vessel diameter regardless of treatment group. Semaglutide increased central retinal thickness compared to placebo with ~1 % (3.8 μm 95 % CI [0.9;6.7], p = 0.009) with no changes in the empagliflozin or combination group.CONCLUSION: Neither semaglutide, empagliflozin nor the combination alters markers of retinal function. The effect of semaglutide on central retinal thickness was small, but the clinical significance is uncertain.

AB - AIMS: Semaglutide and empagliflozin have shown cardiovascular protection. In SUSTAIN-6, semaglutide was associated with an increased risk of diabetic retinopathy. We investigated whether changes in retinal oxygenation, retinal vascular autoregulation, and central retinal thickness are altered by semaglutide, empagliflozin or the combination.METHODS: This study was a prespecified, secondary outcome from a randomised, 32 weeks partly placebo-controlled, partly open-label, clinical trial on the effects of semaglutide and empagliflozin on arterial stiffness and kidney oxygenation. A total of 120 participants with type 2 diabetes, established or high risk of cardiovascular disease and age ≥50 years were randomised into four parallel groups (semaglutide, empagliflozin, the combination or tablet placebo, n = 30 for each group). We primarily hypothesized that semaglutide would increase venular oxygenation.RESULTS: We found no changes in retinal arteriolar, venular or venular-arteriolar oxygenation nor in retinal vessel diameter regardless of treatment group. Semaglutide increased central retinal thickness compared to placebo with ~1 % (3.8 μm 95 % CI [0.9;6.7], p = 0.009) with no changes in the empagliflozin or combination group.CONCLUSION: Neither semaglutide, empagliflozin nor the combination alters markers of retinal function. The effect of semaglutide on central retinal thickness was small, but the clinical significance is uncertain.

KW - Diabetic retinopathy

KW - Glucagon-like peptide 1 receptor agonist

KW - Oximetry

KW - Sodium-glucose transporter 2 inhibitors

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JO - Journal of Diabetes and its Complications

JF - Journal of Diabetes and its Complications

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Gullaksen S , Vernstrøm L, Sørensen SS, Funck KL , Petersen L , Bek T et al. Effects of semaglutide and empagliflozin on oxygenation, vascular autoregulation, and central thickness of the retina in people with type 2 diabetes: A prespecified secondary analysis of a randomised clinical trial. Journal of Diabetes and its Complications. 2023 May;37(5):1-7. 108472. doi: 10.1016/j.jdiacomp.2023.108472

Effects of semaglutide and empagliflozin on oxygenation, vascular autoregulation, and central thickness of the retina in people with type 2 diabetes: A prespecified secondary analysis of a randomised clinical trial

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