A Comparison of Exenatide and Insulin Glargine

A Comparison of Exenatide and Insulin Glargine on Glycemic Variability in T2DM Patients Inadequately Controlled With Metformin Monotherapy

This is a 16-week, Single-center, Randomized, Open Label, Parallel Controlled Group Comparison of the Comprehensive Glycemic Control of Exenatide and Insulin Glargine on Type 2 Diabetes Patients Inadequately Controlled With Metformin Monotherapy.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: exenatide; Drug: Insulin glargine

Detailed Description

Screening will be made to select eligible patients, then 44 patients receiving a stable dose of metformin (≥1500 mg daily) will be randomized (1:1) to receive exenatide or insulin glargine for 16 weeks. Exenatide will be administered twice daily by subcutaneous injection 30- 60 minutes before breakfast and dinner; the dose was 5 μg twice-daily for the first 4 weeks of treatment and 10 μg thereafter. Insulin glargine will be administered once daily at bedtime by subcutaneous injection. The dose of insulin glargine will initiate at ≥8 IU once-daily, and titrate based on a dosing algorithm targeting fasting blood glucose (FPG)<6.1 mmol/L. Titration is only allowed in first 4 weeks. At the end of the study, data will be collected and analyzed.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • at Division of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing 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:

1. Provision of informed consent prior to any study specific procedures
2. Type2 diabetic patients had been on stable, maximum tolerated doses of metformin (≧1500mg/d, ≧8 weeks)
3. Male or female age ≧ 18 years and ≦70 years old
4. HbA1c ≧7.0 and ≦10%
5. BMI ≧ 24 kg/m2

Exclusion Criteria:

1. Known or suspected allergy to trial products or related products.
2. Impaired renal function defined as serum-creatinine ≥ 1.5 mg/dl (≥ 133 umol/l).
3. Acute or chronic disease which may cause tissue hypoxia such as respiratory failure or shock.
4. Abnormal liver function, alanine transaminase or aspartate aminotransferase ≥ 3 fold normal upper limit, Total bilirubin ≥ 2 normal upper limit, acute alcohol intoxication, alcoholism.
5. Subjects has a clinically significant, active (or over the past 12 months) cardiovascular history (including a history of myocardial infarction (MI), arrhythmias or conduction delays on ECG, unstable angina, or decompensated heart failure (New York Heart Association-class Ⅲ and Ⅳ).
6. Proliferative retinopathy or muscular oedema requiring acute treatment.
7. Pregnant or positive pregnancy test at screening, nursing mother, or unwillingness to use adequate contraception (adequate contraceptive measures are sterilization, intrauterine device, oral contraceptives or barrier methods).
8. Treatment with systemic corticosteroids within the past two months prior to screening.
9. Type 1 diabetes mellitus.
10. Receipt of any investigational drug within 1 month prior to this trial.

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
Active Comparator: exenatide; 5 μg BID for the first 4 weeks of treatment and 10 μg thereafter	Drug: exenatide; 5 μg BID for the first 4 weeks of treatment and 10 μg thereafter.; Other Names: Byetta.Lilly; Drug: Insulin glargine; ≥8 IU QD, and titrate based on a dosing algorithm targeting FPG <6.1 mmol/L. Titration is only allowed in first 4 weeks.; Other Names: Lantus,Sanofi Aventis
Active Comparator: Insulin glargine; ≥8 IU QD, and titrate based on a dosing algorithm targeting FPG <6.1 mmol/L. Titration is only allowed in first 4 weeks.	Drug: exenatide; 5 μg BID for the first 4 weeks of treatment and 10 μg thereafter.; Other Names: Byetta.Lilly; Drug: Insulin glargine; ≥8 IU QD, and titrate based on a dosing algorithm targeting FPG <6.1 mmol/L. Titration is only allowed in first 4 weeks.; Other Names: Lantus,Sanofi Aventis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean amplitude of glycemic excursions (MAGE) change from baseline by continuous glucose monitoring system (CGMS)	1±3day；112±3d

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycemic variability	continuous overlapping net glycemic action (CONGA) and mean of daily differences (MODD)	1±3day；112±3d
Glucose control	Glycosylated hemoglobin A 1c (HbA1c), FBG, postprandial blood glucose (PBG)	-7±3d；112±3d；
oxidative stress markers	plasma concentrations of superoxide dismutase (SOD), malondialdehyde, 8-iso-prostaglandin-F2α (8-iso-PGF2α) and urine concentrations of 8-iso-PGF2α;	1±3d；28±3d；56±3d；84±3d；112±3d
inflammatory markers	plasma concentrations of interleukin-1(IL-1), interleukin-18(IL-18), adiponectin, toll-like receptor 4(TLR-4) and phosphorylated-nuclear factor-kappaB 65 (pNF-κB 65) in white blood cells	1±3d；28±3d；56±3d；84±3d；112±3d
endothelial function	plasma total nitric oxide synthase (tNOS), inducible nitric oxide synthase (iNOS), nitric oxide (NO)	1±3d；28±3d；56±3d；84±3d；112±3d
beta-cell function and insulin resistance	homeostasis model assessment-β, homeostasis model assessment -insulin resistance, plasma glucagon, body mass index (BMI), waist-hip ratio	1±3d；112±3d；
body composition	fat mass, lean tissue, body weight, waist circumference	1±3d；112±3d

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with exenatide or insulin glargine adverse events as a measure of safety and tolerability:	hypoglycemia reaction; blood glucose lower than 3.1mmol/L; nausea, vomiting, diarrhea, anorexia or abdominal pain after exenatide subcutaneous injection.	-7±3d；1±3d；7±2d；14±3d；21±2d；28±3d；35±3d；56±3d；84±3d；112±3d
Exploratory Objective assessed by the relationships between oxidative stress and inflammatory markers and MAGE	Whether there is linear correlation between oxidative stress markers and MAGE, and between inflammatory markers and MAGE, and correlation coefficient of each correlation	1±3d；112±3d

Collaborators and Investigators

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Investigators: Principal Investigator: Dalong Zhu, MD PhD, The Affiliated Drum Tower Hospital of Nanjing University

Publications and helpful links

General Publications

• Yin TT, Bi Y, Li P, Shen SM, Wang WM, Jiang C, Gao CX, Wang Y, Gao LJ, Zhu DL, Feng WH. Effects of exenatide versus insulin glargine on body composition in overweight and obese T2DM patients: a randomized controlled trial. Nutr Metab (Lond). 2018 Oct 1;15:67. doi: 10.1186/s12986-018-0295-6. eCollection 2018.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: October 29, 2014
• First Submitted That Met QC Criteria: December 24, 2014
• First Posted (Estimate): December 25, 2014

Study Record Updates

• Last Update Posted (Actual): February 23, 2017
• Last Update Submitted That Met QC Criteria: February 21, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: exenatide; insulin glargine
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Insulin Glargine; Exenatide
• Other Study ID Numbers: ISSEXEN0034

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED