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

Official title

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

Overview

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.

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 superior to glargine plus prandial insulin therapy in overweight/obese patients with uncontrolled type 2 diabetes.

Interventions

• 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.
• 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.

Primary outcome measures

• the proportion of patients with HbA1c < 7.0% without experiencing hypoglycemia and without weight gain,with a superiority margin of 3% [Time frame: 24 weeks]

Secondary outcome measures (11)

• the proportion of patients with hypoglycemia [Time frame: 24 weeks]
• changes in HbA1c [Time frame: 24 weeks]
• changes from baseline in FPG(mmol/L) [Time frame: 24 weeks]
• changes in body weight ( kilograms) [Time frame: 24 weeks]
• changes in prandial insulin dosage （per kilogram） [Time frame: 24 weeks]
• changes in visceral as assessed by dual x-ray absorptiometry (DXA) [Time frame: 24 weeks]
• number of participants with abnormal laboratory values and/or adverse events that are related to treatment [Time frame: 24 weeks]
• changes in serum c-peptide level [Time frame: 24 weeks]
• changes in systolic pressure [Time frame: 24 weeks]
• changes in diastolic pressure [Time frame: 24 weeks]
• changes in serum lipid profile [Time frame: 24 weeks]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The first afilliated hospital of Xiamen university — Xiamen

Identifiers

NCT: NCT03087032 · KYH2017-002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗