Top

Published in:

Open Access 01-02-2019 | Diabetes | Original Research

Effect of Dulaglutide Versus Liraglutide on Glucose Variability, Oxidative Stress, and Endothelial Function in Type 2 Diabetes: A Prospective Study

Authors: Hiroe Nagaike, Makoto Ohara, Yo Kohata, Munenori Hiromura, Masako Tomoyasu, Michiya Takada, Takeshi Yamamoto, Toshiyuki Hayashi, Tomoyasu Fukui, Tsutomu Hirano

Published in: Diabetes Therapy | Issue 1/2019

Abstract

Introduction

To compare the effect of dulaglutide and liraglutide on oxidative stress and endothelial function in patients with type 2 diabetes mellitus (T2DM).

Methods

Twenty-two patients with T2DM who received treatment with liraglutide for at least 12 weeks were randomized to either continue liraglutide or receive dulaglutide for 24 weeks. The primary end points were changes in the diacron-reactive oxygen metabolite (d-ROMs) test, as a marker of oxidative stress, and endothelial function, as determined by the reactive hyperemia index (RHI). The secondary end points were changes in body weight (BW), glucose variability, diabetes treatment satisfaction questionnaire (DTSQ) score, and eating behavior.

Results

There were no significant differences in changes in d-ROMs and logarithmic-scaled RHI (L-RHI) between the two groups after 24 weeks of treatment. Notably, the treatment with dulaglutide was superior to that with liraglutide in terms of mean glucose levels and mean amplitude of glycemic excursions following the 24-week treatment. However, in this regard, the outcome following the treatment with dulaglutide was maintained, whereas that with the treatment with liraglutide was aggravating. The DTSQ score for “convenience” improved in the dulaglutide group. No statistically significant changes in fasting plasma glucose, hemoglobin A1c, and BW were observed between the two groups.

Conclusion

We showed that once-weekly dulaglutide was comparable to once-daily liraglutide in terms of oxidative stress and endothelial function. Switching from liraglutide to dulaglutide improved convenience by decreasing the number of injections without deteriorating glucose metabolism.

Trial Registration

This trial was registered with the University Hospital Medical Information Network (UMIN no. 000034353) on 10 October 2018.

Available only for authorised users

Emerging Risk Factors Collaboration. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010;375:2215–22. https://doi.org/10.1016/S0140-6736(10)60484-9.CrossRef

Roglic G, Unwin N, Bennett PH, et al. The burden of mortality attributable to diabetes. Diabetes Care. 2005;28:2130–5. https://doi.org/10.2337/diacare.28.9.2130.CrossRefPubMed

Marso SP, Daniels GH, Brown-Frandsen K, LEADER Steering Committee, LEADER Trial Investigators, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311–22.CrossRef

Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with Type 2 Diabetes. N Engl J Med. 2016;375:1834–44. https://doi.org/10.1056/NEJMoa1607141.CrossRefPubMed

Ceriello A. The post-prandial state and cardiovascular disease: relevance to diabetes mellitus. Diabetes Metab Res Rev. 2000;16:125–32. https://doi.org/10.1002/(SICI)1520-7560(200003/04)16:2%3c125:AID-DMRR90%3e3.0.CO;2-4.CrossRefPubMed

Ohara M, Fukui T, Ouchi M, et al. Relationship between daily and day-to-day glycemic variability and increased oxidative stress in type 2 diabetes. Diabetes Res Clin Pract. 2016;122:62–70. https://doi.org/10.1016/j.diabres.2016.09.025.CrossRefPubMed

Torimoto K, Okada Y, Mori H, Tanaka Y. Relationship between fluctuations in glucose levels measured by continuous glucose monitoring and vascular endothelial dysfunction in type 2 diabetes mellitus. Cardiovasc Diabetol. 2013;12:1. https://doi.org/10.1186/1475-2840-12-1.CrossRefPubMedPubMedCentral

Boye KS, Curtis SE, Lage MJ, Garcia-Perez LE. Associations between adherence and outcomes among older, type 2 diabetes patients: evidence from a Medicare Supplemental database. Patient Prefer Adherence. 2016;10:1573–81. https://doi.org/10.2147/PPA.S107543.CrossRefPubMedPubMedCentral

Yamamoto S, Hayashi T, Ohara M, et al. Comparison of liraglutide plus basal insulin and basal-bolus insulin therapy (BBIT) for glycemic control, body weight stability, and treatment satisfaction in patients treated using BBIT for type 2 diabetes without severe insulin deficiency: a randomized prospective pilot study. Diabetes Res Clin Pract. 2018;140:339–46. https://doi.org/10.1016/j.diabres.2018.03.032.CrossRefPubMed

10.

Emoto M, Terauchi Y, Ozeki A, Oura T, Takeuchi M, Imaoka T. A 1-year safety study of dulaglutide in Japanese patients with type 2 diabetes on a single oral hypoglycemic agent: an open-label, nonrandomized, phase 3 trial. Endocr J. 2015;62:1101–14. https://doi.org/10.1507/endocrj.EJ15-0401.CrossRefPubMed

11.

Miyagawa J, Odawara M, Takamura T, Iwamoto N, Takita Y, Imaoka T. Once-weekly glucagon-like peptide-1 receptor agonist dulaglutide is non-inferior to once-daily liraglutide and superior to placebo in Japanese patients with type 2 diabetes: a 26-week randomized phase III study. Diabetes Obes Metab. 2015;17:974–83. https://doi.org/10.1111/dom.12534.CrossRefPubMedPubMedCentral

12.

Takase T, Nakamura A, Yamamoto C, et al. Improvement in treatment satisfaction after switching from liraglutide to dulaglutide in patients with type 2 diabetes: a randomized controlled trial. J Diabetes Investig. 2018. https://doi.org/10.1111/jdi.12906 (Epub ahead of print).

13.

Kuvin JT, Patel AR, Sliney KA, et al. Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude. Am Heart J. 2003;146:168–74. https://doi.org/10.1016/S0002-8703(03)00094-2.CrossRefPubMed

14.

Service FJ, Molnar GD, Rosevear JW, Ackermann E, Gatewood LC, Taylor WF. Mean amplitude of glycemic excursions, a measure of diabetic instability. Diabetes. 1970;19:644–55. https://doi.org/10.2337/diab.19.9.644.CrossRefPubMed

15.

Molnar GD, Taylor WF, Ho MM. Day-to-day variation of continuously monitored glycaemia: a further measure of diabetic instability. Diabetologia. 1972;8:342–8.CrossRef

16.

Monnier L, Colette C, Wojtusciszyn A, et al. Toward defining the threshold between low and high glucose variability in diabetes. Diabetes Care. 2017;40:832–8. https://doi.org/10.2337/dc16-1769.CrossRefPubMed

17.

Gerardi G, Usberti M, Martini G, et al. Plasma total antioxidant capacity in hemodialyzed patients and its relationship to other biomarkers of oxidative stress and lipid peroxidation. Clin Chem Lab Med. 2002;40:104–10. https://doi.org/10.1515/CCLM.2002.019.CrossRefPubMed

18.

Cesarone MR, Belcaro G, Carratelli M, et al. A simple test to monitor oxidative stress. Int Angiol. 1999;18:127–30.PubMed

19.

Schnedl WJ, Lahousen T, Wallner SJ, Krause R, Lipp RW. Silent hemoglobin variants and determination of HbA1c with the high resolution program of the HPLC HA-8160 hemoglobin analyzer. Clin Biochem. 2005;38:88–91. https://doi.org/10.1016/j.clinbiochem.2004.09.016.CrossRefPubMed

20.

Bradley C, Lewis KS. Measures of psychological well-being and treatment satisfaction developed from the responses of people with tablet-treated diabetes. Diabet Med. 1990;7:445–51. https://doi.org/10.1111/j.1464-5491.1990.tb01421.x.CrossRefPubMed

21.

Bradley C. The diabetes treatment satisfaction questionnaire: DTSQ. In: Bradley C, editor. Handbook of psychology and diabetes: a guide to psychological measurement in diabetes research and practice. Chur: Harwood Academic; 1994. p. 111–32.

22.

Inoue K, Maeda N, Kashine S, et al. Short-term effects of liraglutide on visceral fat adiposity, appetite, and food preference: a pilot study of obese Japanese patients with type 2 diabetes. Cardiovasc Diabetol. 2011;10:109. https://doi.org/10.1186/1475-2840-10-109.CrossRefPubMedPubMedCentral

23.

Lau KK, Wong YK, Chan YH, et al. Prognostic implications of surrogate markers of atherosclerosis in low to intermediate risk patients with type 2 diabetes. Cardiovasc Diabetol. 2012;11:101. https://doi.org/10.1186/1475-2840-11-101.CrossRefPubMedPubMedCentral

24.

Miyagawa J, Odawara M, Takamura T, Iwamoto N, Takita Y, Imaoka T. Once-weekly glucagon-like peptide-1 receptor agonist dulaglutide is non-inferior to once-daily liraglutide and superior to placebo in Japanese patients with type 2 diabetes: a 26-week randomized phase III study. Diabetes Obed Metab. 2015;17:974–83. https://doi.org/10.1111/dom.12534.CrossRef

25.

Odawara M, Miyagawa J, Iwamoto N, Imaoka T, Takamuta T. Once-weekly glucagon-like peptide-1 receptor agonist dulaglutide significantly decreases glycated haemoglobin compared with once-daily liraglutide in Japanese patients with type 2 diabetes: 52 weeks of treatment in a randomized phase III study. Diabetes Obed Metab. 2016;18.249–57. https://doi.org/10.1111/dom.12602.

26.

Jin SM, Kim TH, Bae JC, Hur KY, Lee MS, Lee MK. Clinical factors associated with absolute and relative measures of glycemic variability determined by continuous glucose monitoring: an analysis of 480 subjects. Diabetes Res Clin Pract. 2014;104:266–72. https://doi.org/10.1016/j.diabres.2014.02.003.CrossRefPubMed

27.

Ohara M, Nagaike H, Goto S, et al. Improvements of ambient hyperglycemia and glycemic variability are associated with reduction in oxidative stress for patients with type 2 diabetes. Diabetes Res Clin Pract. 2018;139:253–61. https://doi.org/10.1016/j.diabres.2018.02.017.CrossRefPubMed

28.

Ceriello A, Novials A, Ortega E, et al. Glucagon-like peptide 1 reduces endothelial dysfunction, inflammation, and oxidative stress induced by both hyperglycemia and hypoglycemia in type 1 diabetes. Diabetes Care. 2013;36:2346–50. https://doi.org/10.2337/dc12-2469.CrossRefPubMedPubMedCentral

29.

Ceriello A, Novials A, Canivell S, et al. Simultaneous GLP-1 and insulin administration acutely enhances their vasodilatory, antiinflammatory, and antioxidant action in type 2 diabetes. Diabetes Care. 2014;37:1938–43. https://doi.org/10.2337/dc13-2618.CrossRefPubMed

30.

Dandona P, Chaudhuri A, Ghanim H, Mohanty P. Insulin as an anti-inflammatory and antiatherogenic modulator. J Am Coll Cardiol. 2009;53:S14–20. https://doi.org/10.1016/j.jacc.2008.10.038.CrossRefPubMed

31.

Oeseburg H, de Boer RA, Buikema H, van der Harst P, van Gilst WH, Silljé HH. Glucagon-like peptide 1 prevents reactive oxygen species-induced endothelial cell senescence through the activation of protein kinase A. Arterioscler Thromb Vasc Biol. 2010;30:1407–14. https://doi.org/10.1161/ATVBAHA.110.206425.CrossRefPubMed

32.

Klonoff DC, Buse JB, Nielsen LL, et al. Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin. 2008;24:275–86. https://doi.org/10.1185/030079908X253870.CrossRefPubMed

33.

Yang SH, Xu RX, Cui CJ, et al. Liraglutide downregulates hepatic LDL receptor and PCSK9 expression in HepG2 cells and db/db mice through a HNF-1a dependent mechanism. Cardiovasc Diabetol. 2018;17:48. https://doi.org/10.1186/s12933-018-0689-9.CrossRefPubMedPubMedCentral

Title: Effect of Dulaglutide Versus Liraglutide on Glucose Variability, Oxidative Stress, and Endothelial Function in Type 2 Diabetes: A Prospective Study
Authors: Hiroe Nagaike
Makoto Ohara
Yo Kohata
Munenori Hiromura
Masako Tomoyasu
Michiya Takada
Takeshi Yamamoto
Toshiyuki Hayashi
Tomoyasu Fukui
Tsutomu Hirano
Publication date: 01-02-2019
Publisher: Springer Healthcare
Keywords: Diabetes
Dulaglutid
Liraglutide
Type 2 Diabetes
Published in: Diabetes Therapy / Issue 1/2019
Print ISSN: 1869-6953
Electronic ISSN: 1869-6961
DOI: https://doi.org/10.1007/s13300-018-0560-8

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Effect of Dulaglutide Versus Liraglutide on Glucose Variability, Oxidative Stress, and Endothelial Function in Type 2 Diabetes: A Prospective Study

Abstract

Introduction

Methods

Results

Conclusion

Trial Registration

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusion

Trial Registration

Please log in to get access to this content

Other articles of this Issue 1/2019

Unmet Needs in the Management of Type 2 Diabetes Mellitus Patients Starting Insulin Therapy with Basal or Premix Insulin in Routine Clinical Practice in Serbia

A Summary of 2018 and What Lies Ahead for Diabetes Therapy in 2019

Successful Outcomes with Insulin Degludec in Pregnancy: A Case Series

Correction to: Insulin Injection Technique in China Compared with the Rest of the World

A Case of Fulminant Type 1 Diabetes with Gastric and Urinary Retention

Efficacy and Safety of IDegAsp Versus BIAsp 30, Both Twice Daily, in Elderly Patients with Type 2 Diabetes: Post Hoc Analysis of Two Phase 3 Randomized Controlled BOOST Trials

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page