Addition of liraglutide in patients with Type 2 diabetes well controlled on metformin monotherapy improves several markers of vascular function
Abstract
Diabet. Med. 29, 1115–1118 (2012) Aims The aim of this study was to investigate the vascular effects of liraglutide in patients well controlled on metformin monotherapy. Methods Forty‐four patients with Type 2 diabetes were included in the study. Main inclusion criteria were: pretreatment with metformin on a stable dosage, HbA 1c < 53 mmol/mol (7.0%), age 30–65 years. Patients were randomized to receive additional liraglutide or to remain on metformin monotherapy. After 6 weeks (1.2 mg) and after 12 weeks (1.8 mg), venous blood was taken for the measurement of several laboratory markers characterizing vascular and endothelial function. In addition, retinal microvascular endothelial function and arterial stiffness were measured. Results HbA 1c levels declined from 45 ± 4 mmol/mol (6.3 ± 0.4%; mean ± sd) to 40 ± 3 mmol/mol (5.8 ± 0.3%) during liraglutide treatment. Asymmetric dimethylarginin was reduced by liraglutide treatment from 0.39 ± 0.08 to 0.35 ± 0.06 μmol/l, E‐selectin from 43.6 ± 15.4 to 40.8 ± 15.1 ng/ml, plasminogen activator inhibitor 1 from 861.6 ± 584.3 to 666.1 ± 499.4 ng/ml and intact proinsulin from 9.0 ± 7.2 to 7.0 ± 4.8 pmol/l at 12 weeks of treatment. The microvascular response to flicker light increased from 7.0 ± 15.1 to 15.4 ± 11.5% after 6 weeks and to 11.1 ± 9.9% after 12 weeks. No change could be observed for high‐sensitivity C‐reactive protein, monocyte chemotactic protein 1, vascular cell adhesion molecule or arterial stiffness parameters. Conclusions In patients with Type 2 diabetes, well controlled with metformin monotherapy, addition of liraglutide improves several cardiovascular risk markers beyond glycaemic control.
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Type 2 diabetes is associated with elevated oxidative stress and chronic low-grade inflammation, which contribute to atherosclerosis, endothelial dysfunction, and microvascular damage.
“A key pathophysiological element involves elevated oxidative stress and chronic, low-grade inflammation, which significantly contribute to the development of atherosclerosis, endothelial dysfunction, and microvascular damage (2–5).”
Several trials included in this evaluation showed decreases in inflammatory markers combined with improvements in surrogate cardiovascular markers such as flow-mediated dilation, epicardial adipose tissue, carotid intima-media thickness, and endothelial cell biomarkers.
“Our evaluation included several trials that showed decreases in inflammatory markers combined with improvements in surrogate cardiovascular markers such as flow-mediated dilation, epicardial adipose tissue, carotid intima-media thickness, and endothelial cell biomarkers (4, 14).”
Sensitivity analysis for MCP-1 showed overall estimates were affected by excluding Forst et al., with statistical significance changing from p = 0.21 to p = 0.04.
“Sensitivity analysis for MCP-1 showed that the overall estimates were affected by excluding the study conducted by Forst et al. 79 (SMD: À0.37, 95% CI: [À0.72,À0.02]), as the statistical significance changed from p = 0.21 to p = 0.04 (Supplementary Figure 3H).”
From The effect of <scp>GLP</scp> ‐1 receptor agonists on circulating inflammatory markers in type 2 diabetes patients: A systematic review and meta‐analysis (2025) · cites this paper as [79]
Cites
Ban, K., Noyan-Ashraf, M. H., Hoefer, J., Bolz, S.-S., Drucker, D. J., & Husain, M. (2008) · Circulation · doi:10.1161/circulationaha.107.739938 · Cited by 1,057 · see citing works
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Knudsen, L. B., & Lau, J. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00155 · Cited by 970 · see citing works
Rakipovski, G., Rolin, B., Nøhr, J., Klewe, I., Frederiksen, K. S., Augustin, R., Hecksher-Sørensen, J., Ingvorsen, C., Polex-Wolf, J., & Knudsen, L. B. (2018) · JACC: Basic to Translational Science · doi:10.1016/j.jacbts.2018.09.004 · Cited by 509 · see citing works
Cherney, D. Z., Perkins, B. A., Soleymanlou, N., Har, R., Fagan, N., Johansen, O., Woerle, H.-J., von Eynatten, M., & Broedl, U. C. (2014) · Cardiovascular Diabetology · doi:10.1186/1475-2840-13-28 · Cited by 470 · see citing works
Buse, J. B., Vilsbøll, T., Thurman, J., Blevins, T. C., Langbakke, I. H., Bøttcher, S. G., & Rodbard, H. W. (2014) · Diabetes Care · doi:10.2337/dc14-0785 · Cited by 259 · see citing works
Liraglutide causes large and rapid epicardial fat reduction
Iacobellis, G., Mohseni, M., Bianco, S. D., & Banga, P. K. (2017) · Obesity · doi:10.1002/oby.21718 · Cited by 251 · see citing works
Bray, J. J. H., Foster‐Davies, H., Salem, A., Hoole, A. L., Obaid, D. R., Halcox, J. P. J., & Stephens, J. W. (2021) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14399 · Cited by 194 · see citing works
“They comprised 6749 patients (inflammation evaluated in 6560, oxidative stress in 701 patients), included a median (IQR) study population of 60 (33-122) participants, and had a median (IQR) follow-up of 6 months (84-182 days).”
BackgroundKrasner, N. M., Ido, Y., Ruderman, N. B., & Cacicedo, J. M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0097554 · Cited by 186 · see citing works
Seufert, J., & Gallwitz, B. (2014) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12251 · Cited by 156 · see citing works
Lambadiari, V., Pavlidis, G., Kousathana, F., Varoudi, M., Vlastos, D., Maratou, E., Georgiou, D., Andreadou, I., Parissis, J., Triantafyllidi, H., et al. (2018) · Cardiovascular Diabetology · doi:10.1186/s12933-017-0646-z · Cited by 146 · see citing works
Aronis, K. N., Chamberland, J. P., & Mantzoros, C. S. (2013) · Metabolism · doi:10.1016/j.metabol.2013.04.010 · Cited by 104 · see citing works
Anti-inflammatory properties of antidiabetic drugs: a “promised land” in the COVID-19 era?
Katsiki, N., & Ferrannini, E. (2020) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2020.107723 · Cited by 91 · see citing works
Ren, Y., Chen, Y., Zheng, W., Kong, W., Liao, Y., Zhang, J., Wang, M., & Zeng, T. (2025) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.16366 · Cited by 59 · see citing works
Forst, T., Weber, M. M., & Pfützner, A. (2012) · Experimental Diabetes Research · doi:10.1155/2012/635472 · Cited by 44 · see citing works
Self-citationSun, F., Wu, S., Guo, S., Yu, K., Yang, Z., Li, L., Zhang, Y., Ji, L., & Zhan, S. (2015) · Endocrine · doi:10.1007/s12020-014-0373-0 · Cited by 44 · see citing works
Treatment potential of the GLP-1 receptor agonists in type 2 diabetes mellitus: a review
Østergaard, L., Frandsen, C. S., & Madsbad, S. (2016) · Expert Review of Clinical Pharmacology · doi:10.1586/17512433.2016.1121808 · Cited by 38 · see citing works
Tate, M., Chong, A., Robinson, E., Green, B. D., & Grieve, D. J. (2015) · British Journal of Pharmacology · doi:10.1111/bph.12943 · Cited by 33 · see citing works
Du, Q., Wang, Y.-J., Yang, S., Zhao, Y.-Y., & Han, P. (2014) · Advances in Therapy · doi:10.1007/s12325-014-0164-2 · Cited by 26 · see citing works
Pharmacological profile, efficacy and safety of lixisenatide in type 2 diabetes mellitus
Forst, T., & Pfützner, A. (2013) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2013.838559 · Cited by 25 · see citing works
Self-citationPfützner, A., Hermanns, I., Ramljak, S., Demircik, F., Pfützner, A. H., Kann, P. H., & Weber, M. M. (2015) · Journal of Diabetes Science and Technology · doi:10.1177/1932296815607862 · Cited by 12 · see citing works
Self-citationZhao, F., Wang, H., Li, S., Yun, H., & Su, W. (2026) · PeerJ · doi:10.7717/peerj.20710 · Cited by 6 · see citing works
Kanbay, M., Shah, E., AlShiab, R., Ozbek, L., Ay, S., Rustamov, A., Covic, A., Mallamaci, F., & Zoccali, C. (2026) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.71106 · Cited by 4 · see citing works
Alrasheed, T., Mostafa, M. E. A., Madkhali, M. A., & Khairy, H. A. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1734549 · Cited by 4 · see citing works
- Authors
- Forst, T., Michelson, G., Ratter, F., Weber, M. M., Anders, S., Mitry, M., Wilhelm, B., & Pfützner, A.
- Affiliations
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Novo Nordisk (Germany) (DE)
- Johannes Gutenberg University Mainz (DE)
- Corresponding author
- Forst, T.
- Venue
- Diabetic Medicine
- Publisher
- Wiley
- Published
- 2012-08-13
- Volume
- 29
- Issue
- 9
- Pages
- 1115-1118
- ISSN
- 0742-3071 (ISSN-L)
- 1464-5491
- OpenAlex
- W2097848179
- Cited by
- 75
- References
- 1
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 4 · 2023: 1 · 2022: 5 · 2021: 2 · 2020: 4 · 2019: 3 · 2018: 4 · 2017: 8 · 2016: 1 · 2015: 9 · 2014: 12 · 2013: 9 · 2012: 4
- FWCI
- 8.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetic Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- liraglutide, type 2 diabetes, metformin monotherapy, vascular function, endothelial function, arterial stiffness, asymmetric dimethylarginine, E-selectin, plasminogen activator inhibitor-1, proinsulin, cardiovascular risk markers, glycemic control
- MeSH terms
- Liraglutide, Adult, Aged, Arginine, Blood Glucose, Diabetes Mellitus, Type 2, Drug Therapy, Combination, Endothelium, Vascular, Female, Humans, Hypoglycemic Agents, Male, Metformin, Microcirculation, Middle Aged, Proinsulin, Prospective Studies, Biomarkers, Plasminogen Activator Inhibitor 1, E-Selectin, Glucagon-Like Peptide 1
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