Comparison of Exenatide vs. Biphasic Insulin Aspart 30 on Glucose Variability in Type 2 Diabetes

Comparison of Exenatide vs. Biphasic Insulin Aspart 30 on Glucose Variability in Type 2 Diabetes : a Randomised Open Parallel-controlled Study

This is a multi-centre, open-label, randomized, parallel trial to compare the effect of Exenatide versus Biphasic insulin Aspart 30 on glucose variability and inflammatory markers in type 2 diabetes mellitus (T2DM) patients inadequately controlled with metformin monotherapy.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Exenatide; Drug: Biphasic insulin Aspart 30

Detailed Description

Studies have showed that fluctuations of glucose seem to have more deleterious effects than sustained hyperglycaemia in the development of diabetic complications. The present randomized controlled trial was designed with primary aim to evaluate glycaemic fluctuation in the comparison between twice-daily Exenatide and other treatment paradigm (e.g. insulin Aspart 30).

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Xijing Hospital, Fourth Military Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provision of informed consent prior to any study specific procedures.
• Men and women (non-pregnant and using a medically approved birth-control method) aged between 18 and 70 years at screening.
• Confirmed type 2 diabetes with history of at least half a year.
• Treatment with stable, maximum tolerated doses of metformin (≧1500mg/d, ≧3 months).
• HbA1c ≥ 7.5% and ≤ 10.0% at screening or within 4 weeks prior to screening (by local laboratory).
• Body mass index: 21-35 kg/m^2.

Exclusion Criteria:

• Women who are pregnant, intending to become pregnant during the study period, currently lactating females, or women of child-bearing potential not using highly effective, medically approved birth control methods.

• Diagnosis or history of:

  1. Type 1 diabetes mellitus, diabetes resulting from pancreatic injury or secondary forms of diabetes, e.g., acromegaly or Cushing's syndrome.
  2. Acute metabolic diabetic complications such as ketoacidosis or hyperosmolar coma within the past 6 months.
• Previous treatment with any dipeptide peptidase-4 (DPP4) inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonists within the past one year.
• History of hypersensitivity reaction (e.g., anaphylaxis, angioedema, exfoliative skin conditions) to dipeptide peptidase-4 inhibitor (DPP4) or Acarbose.
• Treatment with any anti-diabetic medication for more than 7 consecutive days other than metformin in the last 3months prior to screening.
• Treatment with systemic glucocorticoids (oral, intravenous) for more than consecutive 7 days within the past 6 months.
• Triglycerides (fasting) > 4.5 mmol/L (> 400 mg/dL) at screening or within 4 weeks prior to screening (by local laboratory).

• Patients with clinically apparent liver disease characterized by either one of the following:

  1. Alanine transaminase (ALT) or aspartate aminotransferase (AST) > 3x upper limit of normal (ULN) confirmed on two consecutive measurements (by local laboratory) within 4 weeks prior to screening period
  2. Impaired excretory (e.g. hyperbilirubinemia) and/or synthetic function, or other conditions of decompensated liver disease such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites and bleeding from oesophageal varices.
  3. Acute viral or active autoimmune, alcoholic, or other types of hepatitis.
• Patients with moderate /severe renal impairment or end-stage renal disease (estimated Glomerular Filtration Rate ≤ 60 mL/min calculated by using the abbreviated equation developed by the Modification of Diet in Renal Disease (MDRD) study with modification for the Chinese population) at screening or within 4 weeks prior to screening (by local laboratory)
• Congestive heart failure defined as New York Heart Association (NYHA) class III or IV.
• Significant cardiovascular history within the past 3 months prior to screening defined as: myocardial infarction, coronary angioplasty or bypass graft(s), valvular disease or repair, unstable angina pectoris, transient ischemic attack, or cerebrovascular accident.
• History of chronic pancreatitis or idiopathic acute pancreatitis.
• History of gastrointestinal disease including gastroenterostomy, enterectomy, Roemheld Syndrome, severe hernia, intestinal obstruction, intestinal ulcer.
• History of genetic galactose intolerance, Lapp lactase deficiency and glucose-galactose malabsorption.
• History of medullary thyroid carcinoma.
• Diagnosed and/or treated malignancy (except for basal cell skin cancer, in situ carcinoma of the cervix, or in situ prostate cancer) within the past 5 years.
• History of organ transplant or acquired immunodeficiency syndrome (AIDS).
• History of alcohol abuse or illegal drug abuse within the past 12 months.
• Potentially unreliable patients and those judged by the Investigator to be unsuitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exenatide; Exenatide (Colorless transparent liquid, comes in a prefilled pen.5ug/10ug, AstraZeneca) should be initiated, 60 minutes pre-breakfast and pre-supper, at 5ug twice a day for 4 weeks and then titrated up at 10ug twice a day until the completion of the study.	Drug: Exenatide; Other Names: Byetta
Active Comparator: Biphasic insulin Aspart 30; Biphasic insulin Aspart 30 (Colorless transparent liquid, 100u/mL, 3ml each, Novo Nordisk), subcutaneous injection, starting at a dose of 0.2-0.4 IU/kg, or 10～12 IU/d assigned in pre-breakfast and pre-supper in a 1:1 ratio. The adjustment of insulin dose is instructed to achieve an optimal balance between glycaemic control and risk of hypoglycaemia as dictated by best clinical practice, titrated to glucose targets of fasting plasma glucose (FPG) and pre-supper <7 mmol/L.	Drug: Biphasic insulin Aspart 30

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change of mean amplitude of glycemic excursions	from baseline to Week 16

Secondary Outcome Measures

Outcome Measure	Time Frame
HbA1c	at baseline and Week 16
Hours of hypoglycemia as measured by continuous glucose monitoring system (CGMS)	at baseline and Week 16
Blood pressure	at baseline and Week 16
Lipids	at baseline and Week 16
Body mass index	at baseline and Week 16
Waist circumference	at baseline and Week 16
Monocyte chemotactic protein-1 (MCP-1)	at baseline and Week 16
High-sensitivity C-reactive protein (hs-CRP)	at baseline and Week 16
Urinary albumin	at baseline and Week 16
Number of participants with adverse events/severe adverse events	from baseline to Week 16
Number of participants with clinical hypoglycemia	from baseline to Week 16

Collaborators and Investigators

• Sponsor: Xijing Hospital
• Collaborators: Xi'an Central Hospital; First Affiliated Hospital Xi'an Jiaotong University; Shaanxi Provincial People's Hospital; Air Force Military Medical University, China; Second Affiliated Hospital of Xi'an Jiaotong University; Xi'an Gaoxin Hospital; Shaanxi Aerospace Hospital; Chang'An Hospital

Publications and helpful links

General Publications

• Wang L, Liu X, Yang W, Lai J, Yu X, Liu J, Gao X, Ming J, Ma K, Xu J, Tian Z, He Q, Ji Q. Comparison of Blood Glucose Variability Between Exenatide and Biphasic Insulin Aspart 30 in Chinese Participants with Type 2 Diabetes Inadequately Controlled with Metformin Monotherapy: A Multicenter, Open-Label, Randomized Trial. Diabetes Ther. 2020 Oct;11(10):2313-2328. doi: 10.1007/s13300-020-00904-z. Epub 2020 Aug 27.
• Xu S, Liu X, Ming J, Ji Q. Comparison of exenatide with biphasic insulin aspart 30 on glucose variability in type 2 diabetes: study protocol for a randomized controlled trial. Trials. 2016 Mar 24;17:160. doi: 10.1186/s13063-016-1258-8.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2015
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: May 11, 2015
• First Submitted That Met QC Criteria: May 17, 2015
• First Posted (Estimate): May 20, 2015

Study Record Updates

• Last Update Posted (Actual): November 14, 2018
• Last Update Submitted That Met QC Criteria: November 11, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Chinese population
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Insulin Aspart; Exenatide; Biphasic Insulins; Insulin aspart, insulin aspart protamine drug combination 30:70
• Other Study ID Numbers: ESR-14-10319