Liraglutide-bolus vs Glargine-bolus Therapy in Overweight/Obese Type 2 Diabetes Patients (LiraGooD) (LiraGooD)

Efficacy and Safety of Liraglutide-bolus (Liraglutide Plus Prandial Insulin) Versus Glargine-bolus Therapy in Overweight / Obese Patients With Uncontrolled Type 2 Diabetes (LiraGooD)--A Multicenter Randomized Controlled Study

The present 24-week, prospective, open-label, randomized, multicenter, parallel group trial is carried to investigate and evaluate the efficacy and safety of Liraglutide in combination with prandial insulin therapy vs insulin glargine in combination with prandial insulin therapy in overweight / obese patients with uncontrolled type 2 diabetes.

Study Overview

• Status: Unknown
• Conditions: Overweight and Obesity; Hyperglycaemia (Diabetic); Type 2 Diabetes Patients
• Intervention / Treatment: Drug: Liraglutide; Drug: insulin glargine

Detailed Description

An increasing number of patients with type 2 diabetes are treated with insulin. Patients with diabetes receiving intensive insulin therapy with various combinations of basal and prandial insulin can be caught in a vicious but common cycle, whereby insulin requirements increase over time, and this in turn contributes to weight gain and hypoglycemia and further increases in insulin dosing. At this stage, clinicians observe a practical limit to the efficacy of insulin titration alone on glucose-lowering and often add or continue metformin to reduce insulin resistance. Injectable glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as liraglutide, are a relatively new addition to our treatment armamentarium. These drugs improve glucose control and insulin sensitivity and contribute to weight loss. Treatment with basal insulin plus GLP-1RAs is well-established in diabetes guidelines and may be as effective as adding prandial insulin therapy. When GLP-1 RAs are started, a preemptive reduction in insulin dosage by 25% to 30% in patients with HbA1c < 9% may reduce the risk for hypoglycemia. In overweight/obese patients with uncontrolled type 2 diabetes treated with more than three oral antidiabetic drugs (OADs) or high doses of premix insulin, Is basal-prandial insulin therapy the option treatment algorithm? Such an intensification strategy carries risk of increased hypoglycaemia and weight gain, both of which are associated with worse long-term outcomes. There have no randomized, controlled trials to evaluate the efficacy and safety of GLP-1 RAs vs insulin glargine added to prandial insulin in overweight/obese patients with uncontrolled type 2 diabetes. So, the current 24-week, prospective, open-label, randomized, multicenter, parallel group trial will be preformed to assess whether Liraglutide plus prandial insulin therapy was noninferior to glargine plus prandial insulin therapy in overweight/obese patients with uncontrolled type 2 diabetes。

• Study Type: Interventional
• Enrollment (Anticipated): 140
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Changqin Liu, MD; Phone Number: +86-133-7698-6106; Email: liuchangqin@xmu.edu.cn
• Study Contact Backup: Name: Xin Zheng, MD; Phone Number: +86-187-0592-9102; Email: 88126386@qq.com

Study Locations

• China
  • Fujian
    • Xiamen, Fujian, China, 361003
      • Recruiting
      • The first afilliated hospital of Xiamen university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age: 18 - 75 years old.
• BMI must be greater than 24 and less than 45 kg/m2
• Patients with type 2 diabetes who met the World Health Organization (who) diagnostic criteria (1999).
• Newly diagnosed type 2 diabetic patients with HbA1c ≥ 9.0%；or patients with uncontrolled type 2 diabetes (HbA1c ≥ 7.5% ) who have received at least two types of oral hypoglycemic drugs (the dose of each drug needs to reach the second largest dose or more), or only insulin (excluding basal-bolus insulin therapy), or insulin with oral hypoglycemic drugs.
• Signed informed consent.

Exclusion Criteria:

• History of pancreatic disease,
• History of medullary thyroid carcinoma
• Lipase level > 3 times above normal,
• Creatinine clearance ≤ 30 mL/min/1.73m2,
• Evidence in the last 6 months of significant heart disease or stroke, including myocardial infarction, unstable angina, coronary bypass and/or percutaneous transluminal coronary angioplasty, congestive heart failure (New York Heart Association Functional Classification III-IV), or severe ischemic heart disease.
• Preparation for pregnancy or having been in pregnancy
• Researchers believe that there are any factors that affect assessing subjects' participation in trial.
• Patients unable to cooperate in clinical trials

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Liraglutide-bolus; 'Liraglutide-bolus'(Liraglutide once-daily plus thrice-daily prandial insulin lispro). Patients will receive adding Liraglutide to prandial insulin Lispro. The starting liraglutide dose was 0.6mg/day, then 1.2mg/day after 1 week and 1.8mg/day after a further week. The dose was maintained until study completion. Dose of insulin Lispro will be instructed on a titration schedule, adjusted every 3 days.	Drug: Liraglutide; Patients will receive adding Liraglutide to prandial insulin Lispro. The starting liraglutide dose was 0.6mg/day, then 1.2mg/day after 1 week and 1.8mg/day after a further week. The dose was maintained until study completion. Dose of insulin Lispro will be instructed on a titration schedule, adjusted every 3 days.; Other Names: Victozaa; Liraglutid; Liroglutide; Liraglutidum; Liraglutide Acetate
ACTIVE_COMPARATOR: Basal-bolus; 'Basal-bolus' (insulin glargine once-daily plus thrice-daily prandial insulin lispro). Patients will receive adding insulin Glargine to prandial insulin Lispro.Dose of insulin will be instructed on a titration schedule, adjusted every 3 days. Patients subcutaneously self-injected once-daily at approximately the same time each day.	Drug: insulin glargine; Individuals randomized to adding insulin Glargine to prandial insulin Lispro will be instructed on a titration schedule, adjusted every 3 days. Patients subcutaneously self-injected once-daily at approximately the same time each day.; Other Names: Lantus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in HbA1c level after 24 weeks,with a noninferiority margin of 0.3%	the net change in glycated hemoglobin level is less than 0.3%	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes from baseline in FPG(mmol/L)	changes from baseline in FPG(mmol/L)	24 weeks
changes in body weight ( kilograms)	changes in body weight( kilograms)	24 weeks
changes in prandial insulin dosage （per kilogram）	changes in prandial insulin dosage （per kilogram）	24 weeks
changes in visceral as assessed by dual x-ray absorptiometry (DXA)	changes in visceral as assessed by dual x-ray absorptiometry (DXA)	24 weeks
number of participants with abnormal laboratory values and/or adverse events that are related to treatment	number of participants with abnormal laboratory values and/or adverse events	24 weeks
changes in abdominal circumference	changes in abdominal circumference	24 weeks
changes in waist circumference	changes in waist circumference	24 weeks
changes in serum c-peptide level	changes in serum c-peptide level	24 weeks
changes in systolic pressure	changes in systolic pressure	24 weeks
changes in diastolic pressure	changes in diastolic pressure	24 weeks
changes in serum lipid profile	changes in serum lipid profile	24 weeks

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Xiamen University
• Investigators: Principal Investigator: Xuejun Li, MD, The first afilliated hospital of Xiamen university

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 10, 2019
• Primary Completion (ANTICIPATED): December 1, 2021
• Study Completion (ANTICIPATED): December 31, 2021

Study Registration Dates

• First Submitted: March 8, 2017
• First Submitted That Met QC Criteria: March 16, 2017
• First Posted (ACTUAL): March 22, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 6, 2020
• Last Update Submitted That Met QC Criteria: August 4, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Liraglutide; Insulin Glargine; Prandial Insulin
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Body Weight; Hyperglycemia; Diabetes Mellitus; Diabetes Mellitus, Type 2; Overweight; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide; Insulin Glargine
• Other Study ID Numbers: KYH2017-002

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No