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

NCT04692415 | Completed Phase 4 DMC

• 1 other identifier: 500-03/16-01/49
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diabetes Mellitus, Type 2

Keywords

Diabetes mellitus type 2; degludec; glargine U300; glucose variability; lipids; arterial stiffness; oxidative stress

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (14)

• Changes from baseline in total cholesterol

  3 months

• Changes from baseline in triglycerides

  3 months

• Changes from baseline in LDL

  3 months

• Changes from baseline in HDL

  3 months

• Changes from baseline in WBC

  3 months

Study Arms (2)

degludec arm

ACTIVE COMPARATOR

25 patients were discontinued their previous therapy and given metformin alone (2 g/day) for seven days. After seven days they were randomized to first receive IDeg-100 In phase one they received IDeg-100 and metformin for 12 weeks. Phase one was followed by a second wash-up period in which patients received metformin alone again for seven days. In phase two, which also lasted for 12 weeks, patients were switched from IDeg-100 to IGlar-300 (and metformin was continued). The initial dose of both insulins was 0.2 IU/kg.

Drug: Degludec

glargine arm

ACTIVE COMPARATOR

25 patients were discontinued their previous therapy and given metformin alone (2 g/day) for seven days. After seven days they were randomized to first receive IGlar-300 In phase one they received IGlar-300 and metformin for 12 weeks. Phase one was followed by a second wash-up period in which patients received metformin alone again for seven days. In phase two, which also lasted for 12 weeks, patients were switched from IGlar-300 to IDeg-100 (and metformin was continued). The initial dose of both insulins was 0.2 IU/kg.

Drug: Glargine U300

Interventions

Degludec DRUG

treatment of DM and it's affect on Glycaemic Variability, Oxidative Stress, Arterial Stiffness and the Lipid Profiles

degludec arm

Glargine U300 DRUG

treatment of DM and it's affect on Glycaemic Variability, Oxidative Stress, Arterial Stiffness and the Lipid Profiles

glargine arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Split, School of Medicine: lead
• Pavle Vrebalov Cindro: collaborator
• Jonatan Vuković: collaborator
• Darko Modun: collaborator
• Božo Smajić: collaborator
• Gordan Kardum: collaborator
• Tina Tičinović Kurir: collaborator
• Doris Rušić: collaborator
• Ana Šešelja Perišin: collaborator
• Josipa Bukić: collaborator

Study Sites (1)

Klinički bolnički Centar Split

Split, 21000, Croatia

Location

Related Publications (17)

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• 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-naive patients with type 2 diabetes. Diabetes Obes Metab. 2019 Apr;21(4):1001-1009. doi: 10.1111/dom.13616. Epub 2019 Jan 8.

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• Rosenstock J, Cheng A, Ritzel R, Bosnyak Z, Devisme C, Cali AMG, Sieber J, Stella P, Wang X, Frias 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.

  PMID: 30104294 BACKGROUND

• Vrebalov Cindro P, Krnic M, Modun D, Vukovic J, Ticinovic Kurir T, Kardum G, Rusic D, Seselja Perisin A, Bukic J. Comparison of the Impact of Insulin Degludec U100 and Insulin Glargine U300 on Glycemic Variability and Oxidative Stress in Insulin-Naive Patients With Type 2 Diabetes Mellitus: Pilot Study for a Randomized Trial. JMIR Form Res. 2022 Jul 8;6(7):e35655. doi: 10.2196/35655.

  PMID: 35802405 DERIVED

• Cindro PV, Krnic M, Modun D, Smajic B, Vukovic J. The differences between insulin glargine U300 and insulin degludec U100 in impact on the glycaemic variability, arterial stiffness and the lipid profiles in insulin naive patients suffering from type two diabetes mellitus - outcomes from cross-over open-label randomized trial. BMC Endocr Disord. 2021 Apr 29;21(1):86. doi: 10.1186/s12902-021-00746-1.

  PMID: 33926446 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

insulin degludec

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant professor

Study Record Dates

• First Submitted: December 20, 2020
• First Posted: December 31, 2020
• Study Start: December 15, 2018
• Primary Completion: June 27, 2019
• Study Completion: June 27, 2019
• Last Updated: December 31, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: at any time
• Access Criteria: health workers, health care organisations, health care providers, drug makers

Locations

CR (1)