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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Liraglutide-bolus | Experimental | '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. |
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| Basal-bolus | Active Comparator | '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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Liraglutide | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| the proportion of patients with HbA1c < 7.0% without experiencing hypoglycemia and without weight gain,with a superiority margin of 3% | the net difference in the proportion of patients with HbA1c < 7.0% without experiencing hypoglycemia and without weight gain is more than 3% | 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| the proportion of patients with hypoglycemia | the proportion of patients with hypoglycemia | 24 weeks |
| changes in HbA1c | changes in HbA1c |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Changqin Liu, MD | Contact | +86-133-7698-6106 | liuchangqin@xmu.edu.cn | |
| Xin Zheng, MD | Contact | +86-187-0592-9102 | 88126386@qq.com |
| Name | Affiliation | Role |
|---|---|---|
| Xuejun Li, MD | The first afilliated hospital of Xiamen university | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The first afilliated hospital of Xiamen university | Recruiting | Xiamen | Fujian | 361003 | China |
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| insulin glargine | Drug | 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. |
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| 24 weeks |
| 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 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 |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D009765 | Obesity |
| D006943 | Hyperglycemia |
| ID | Term |
|---|---|
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
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| ID | Term |
|---|---|
| D000069450 | Liraglutide |
| D000069036 | Insulin Glargine |
| ID | Term |
|---|---|
| D052216 | Glucagon-Like Peptide 1 |
| D004763 | Glucagon-Like Peptides |
| D052336 | Proglucagon |
| D005768 | Gastrointestinal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D049528 | Insulin, Long-Acting |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
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