Insulin Glargine U300 vs Insulin Degludec U100 in Impact on the Glycaemic and Cardiovascular Factors

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

The Differences Between Insulin Glargine U300 and Insulin Degludec U100 in Impact on the Glycaemic Variability, Oxidative Stress, Arterial Stiffness and the Lipid Profiles in Insulin naïve Patients Suffering From Type Two Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04692415
• Other study ID #: 500-03/16-01/49
• Status: Completed
• Phase: Phase 4
• Start date: December 15, 2018
• Est. completion date: June 27, 2019

Study information

• Verified date: December 2020
• Source: University of Split, School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To compare the impact of insulin degludec (IDeg-100) and insulin glargine U300 (IGlar-300) on cardiovascular risk parameters - glycaemic variability (GV), oxidative stress, arterial stiffness and lipid parameters - in insulin naive patients with DMT2.

Description:

We recruited a total of 25 patients (23 completed the study) with T2DM who had uncontrolled disease on two or more oral antidiabetic drugs. After the wash-up period, they were randomized alternately to first receive either IDeg-100 or IGlar-300 along with metformin. Each insulin was applied for 12 weeks. At the beginning and the end of each phase, biochemical and oxidative stress parameters were analysed and augmentation index was measured. On three consecutive days prior to each control point, patients performed a 7-point SMBG profile. Oxidative stress was assessed by measuring thiol groups and hydroperoxides (d-ROM) in serum. For augmentation index measuring, we used SphygmoCor (AtCor Medical, Sydney, Australia) which allow non-invasive measurement of AIx on radial artery using strain gauge transducer placed on the tip of a pencil-type tonometer. This method is based on the principle of applanation tonometry

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: June 27, 2019
• Est. primary completion date: June 27, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• a history of DMT2 for at least 1 year

• aged between 18 and 65 years (women obligatory postmenopausal)

• uncontrolled glycaemia on two or more oral antidiabetic drugs

• no prior use of insulin

• HbA1c =7.5%

• receiving statins (if not on statins, they were put on it)

• not on antiaggregant therapy (if on antiaggregants, they were temporarily excluded from therapy)

Exclusion criteria:

• the presence of malignant disease

• chronic liver disease

• renal impairment with creatinine clearance < 60 ml/s

• severe cardiovascular disease or history of cardiovascular incidents (stroke, myocardial infarction, peripheral amputation)

• rheumatic and autoimmune diseases and the usage of glitazones or anticoagulant therapy

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Degludec
treatment of DM and it's affect on Glycaemic Variability, Oxidative Stress, Arterial Stiffness and the Lipid Profiles
• Glargine U300
treatment of DM and it's affect on Glycaemic Variability, Oxidative Stress, Arterial Stiffness and the Lipid Profiles

Locations

Country	Name	City	State
Croatia	Klinicki bolnicki Centar Split	Split

Sponsors (10)

Lead Sponsor	Collaborator
University of Split, School of Medicine	Ana Šešelja Perišin, Božo Smajic, Darko Modun, Doris Rušic, Gordan Kardum, Jonatan Vukovic, Josipa Bukic, Pavle Vrebalov Cindro, Tina Ticinovic Kurir

Country where clinical trial is conducted

Croatia, 

References & Publications (15)

Aslan I, Kucuksayan E, Aslan M. Effect of insulin analog initiation therapy on LDL/HDL subfraction profile and HDL associated enzymes in type 2 diabetic patients. Lipids Health Dis. 2013 Apr 24;12:54. doi: 10.1186/1476-511X-12-54. — View Citation

Ceriello A, Esposito K, Piconi L, Ihnat MA, Thorpe JE, Testa R, Boemi M, Giugliano D. Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes. 2008 May;57(5):1349-54. doi: 10.2337/db08-0063. Epub 2008 Feb 25. — View Citation

Eckel RH, Wassef M, Chait A, Sobel B, Barrett E, King G, Lopes-Virella M, Reusch J, Ruderman N, Steiner G, Vlassara H. Prevention Conference VI: Diabetes and Cardiovascular Disease: Writing Group II: pathogenesis of atherosclerosis in diabetes. Circulation. 2002 May 7;105(18):e138-43. — View Citation

Gordin D, Saraheimo M, Tuomikangas J, Soro-Paavonen A, Forsblom C, Paavonen K, Steckel-Hamann B, Harjutsalo V, Nicolaou L, Pavo I, Koivisto V, Groop PH. Insulin exposure mitigates the increase of arterial stiffness in patients with type 2 diabetes and albuminuria: an exploratory analysis. Acta Diabetol. 2019 Nov;56(11):1169-1175. doi: 10.1007/s00592-019-01351-4. Epub 2019 May 22. — View Citation

Heise T, Mathieu C. Impact of the mode of protraction of basal insulin therapies on their pharmacokinetic and pharmacodynamic properties and resulting clinical outcomes. Diabetes Obes Metab. 2017 Jan;19(1):3-12. doi: 10.1111/dom.12782. Epub 2016 Sep 26. Review. — View Citation

Home P, Bartley P, Russell-Jones D, Hanaire-Broutin H, Heeg JE, Abrams P, Landin-Olsson M, Hylleberg B, Lang H, Draeger E; Study to Evaluate the Administration of Detemir Insulin Efficacy, Safety and Suitability (STEADINESS) Study Group. Insulin detemir offers improved glycemic control compared with NPH insulin in people with type 1 diabetes: a randomized clinical trial. Diabetes Care. 2004 May;27(5):1081-7. — View Citation

Monnier L, Colette C, Owens DR. Glycemic variability: the third component of the dysglycemia in diabetes. Is it important? How to measure it? J Diabetes Sci Technol. 2008 Nov;2(6):1094-100. — View Citation

Monnier L, Colette C. Glycemic variability: should we and can we prevent it? Diabetes Care. 2008 Feb;31 Suppl 2:S150-4. doi: 10.2337/dc08-s241. — View Citation

Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, Colette C. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA. 2006 Apr 12;295(14):1681-7. — View Citation

Patoulias D, Papadopoulos C, Stavropoulos K, Zografou I, Doumas M, Karagiannis A. Prognostic value of arterial stiffness measurements in cardiovascular disease, diabetes, and its complications: The potential role of sodium-glucose co-transporter-2 inhibitors. J Clin Hypertens (Greenwich). 2020 Apr;22(4):562-571. doi: 10.1111/jch.13831. Epub 2020 Feb 14. Review. — View Citation

Rosenstock J, Cheng A, Ritzel R, Bosnyak Z, Devisme C, Cali AMG, Sieber J, Stella P, Wang X, Frías JP, Roussel R, Bolli GB. More Similarities Than Differences Testing Insulin Glargine 300 Units/mL Versus Insulin Degludec 100 Units/mL in Insulin-Naive Type 2 Diabetes: The Randomized Head-to-Head BRIGHT Trial. Diabetes Care. 2018 Oct;41(10):2147-2154. doi: 10.2337/dc18-0559. Epub 2018 Aug 13. — View Citation

Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000 Aug 12;321(7258):405-12. — View Citation

Tamminen MK, Westerbacka J, Vehkavaara S, Yki-Järvinen H. Insulin therapy improves insulin actions on glucose metabolism and aortic wave reflection in type 2 diabetic patients. Eur J Clin Invest. 2003 Oct;33(10):855-60. — View Citation

Tibaldi J, Hadley-Brown M, Liebl A, Haldrup S, Sandberg V, Wolden ML, Rodbard HW. A comparative effectiveness study of degludec and insulin glargine 300 U/mL in insulin-naïve patients with type 2 diabetes. Diabetes Obes Metab. 2019 Apr;21(4):1001-1009. doi: 10.1111/dom.13616. Epub 2019 Jan 8. — View Citation

Vukovic J, Modun D, Budimir D, Sutlovic D, Salamunic I, Zaja I, Boban M. Acute, food-induced moderate elevation of plasma uric acid protects against hyperoxia-induced oxidative stress and increase in arterial stiffness in healthy humans. Atherosclerosis. 2009 Nov;207(1):255-60. doi: 10.1016/j.atherosclerosis.2009.04.012. Epub 2009 Apr 17. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes from baseline in glucose variability	Glucose variability will be assessed at the beginning and the end of each phase using 3-day 7-point SMBG and calculating coefficient of variation in % out of SMBG recordings	3 months
Primary	Changes from baseline in oxidative stress	Oxidative stress will be assessed at the beginning and the end of each phase by measuring thiol groups and hydroperoxides (d-ROM) in serum	3 months
Primary	Changes from baseline in arterial stiffness after treatment	Oxidative stress will be assessed at the beginning and the end of each phase by measuring augmentation index with SphygmoCor.	3 months
Secondary	Changes from baseline in total cholesterol	Total cholesterol concentration in mmol/L will be assessed at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit	3 months
Secondary	Changes from baseline in triglycerides	Triglyceride concentration in mmol/L will be assessed at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit	3 months
Secondary	Changes from baseline in LDL	Low density lipoprotein cholesterol concentration in mmol/L will be assessed at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit	3 months
Secondary	Changes from baseline in HDL	High density lipoprotein cholesterol concentration in mmol/L will be assessed at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit	3 months
Secondary	Changes from baseline in WBC	White blood count will be assessed at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit	3 months
Secondary	Changes from baseline in RBC	Red blood count will be assessed at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit	3 months
Secondary	Changes from baseline in platelets	Platelets count will be assessed at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit	3 months
Secondary	Changes from baseline in hemoglobin	Hemoglobin concentration in g/L will be assessed in at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit	3 months
Secondary	Changes from baseline in hematocrit	Hematocrit in L/L will be assessed in at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit	3 months
Secondary	Changes from baseline in MCV	Medium cellular volume in fL will be assessed in at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit	3 months
Secondary	Changes from baseline in liver enzymes	ALT, AST and GGT concentration in U/L will be assessed at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit	3 months
Secondary	Changes from baseline in LDH	Lactate dehydrogenase concentration in U/L will be assessed at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit	3 months
Secondary	Changes from baseline in ALP	Alkaline phosphatase concentration in U/L will be assessed at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit	3 months
Secondary	Changes from baseline in CRP	C-reactive protein concentration in mg/L will be assessed at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit	3 months