A Study of Adding Linagliptin to Control Glycemic Variability and HbA1c in Peritoneal Dialysis Patients With Type 2 Diabetes(PDPD) With Premixed Insulin Therapy

Study Overview
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Brief Summary
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In china, there are the most population of type 2 diabetes mellitus (DM) among the world and DM becomes currently the second cause for end-stage renal disease (ESRD). Nearly 50% of insulin-treated PD patients in clinical practice are treated with premixed insulin. Glycemic control in them is very difficult to be achieved mainly due to the uremic status of these patients and glucose exposure from peritoneal dialysate, a higher glycemic variability and higher risk of hypoglycemia. Linagliptin, unlike other DPP-4 inhibitors, has a primarily non-renal elimination route, and does not require dose adjustment for any level of impaired renal function. The aim of this study is to evaluate the effect of linagliptin on glucose variability and glycemic control in peritoneal dialysis patients with type 2 diabetes who are inadequately controlled with premixed insulin therapy. This will be a randomized, double-blind, placebo-controlled, parallel group study to evaluate the effect of linagliptin on glucose variability and glycemic control in peritoneal dialysis patients with type 2 diabetes who are inadequately controlled with premixed insulin therapy.which will be conducted in 8 diabetes centres and/or nephropathy departments in China. After a 4-week run- in period, 232 participants are randomized (1:1) to either premixed insulin combined with linagliptin (5mg/d) group (also named combined group) or premixed insulin alone group (also named insulin group) for 12 weeks. Finally, the primary endpoint is glucose variability indicated by MAGE, secondary endpoints include HbA1c, FPG, PPG, LAGE, SDBG, PT10.0, PT3.9, 1h fasting MBG, 3h postprandial MBG, insulin dosage, hypoglycemia and body weight.

Official Title
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A Randomized, Open, Controlled, Parallel Group Study of Adding Linagliptin to Control Glycemic Variability and HbA1c in Peritoneal Dialysis Patients With Type 2 Diabetes(PDPD) With Premixed Insulin Therapy

Conditions
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Type 2 Diabetes Mellitus, Peritoneal Dialysis

Intervention / Treatment
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* Drug: Linagliptin
* Drug: Humalog Mix 75/25


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetic patients who were treated with insulin regimen; Ages eligible for study:18 years to 80 years; The patients with end-stage kidney disease receiving a regular peritoneal dialysis for at least 3 months; HbA1c ranging from 6.5%-10.5% when screening and randomizing ; Body mass index ranging from 21 to 35 kg/m2. Exclusion Criteria: Having any severe acute or chronic diabetic complications Blood aminotransferase level rising up more than 2 times of the upper normal limit Any severe cardiac disease, severe systemic diseases or malignant tumour Female patients incline to be pregnant Being treated with corticosteroid, immunosuppressing drugs or cytotoxic drugs Poor compliance

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: combined group<br>Drug: linagliptin&premixed insulin Treated with linagliptin 5mg/d combined with premixed insulin for 12 weeks. | Drug: Linagliptin<br>* Take linagliptin 5mg a day.<br>* Other names: Trajenta;Drug: Humalog Mix 75/25<br>* Administer subcutaneous premixed insulin twice a day.<br>* Other names: insulin lispro 75/25;|
| Active Comparator: linsulin group<br>Drug: premixed insulin Treated with premixed insulin for 12 weeks. | Drug: Humalog Mix 75/25<br>* Administer subcutaneous premixed insulin twice a day.<br>* Other names: insulin lispro 75/25;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| glucose variability | The change from baseline to week 12 in glucose variability indicated by MAGE. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c | Changes in HbA1c between two groups | 12 weeks | 
| FPG | Changes in FPG between two groups | 12 weeks | 
| insulin dosage | Changes in FPG at the end between two groups | 12 weeks | 
| body weight | Changes in body weight at the end between two groups | 12 weeks | 
| hypoglycemia | Frequency of hypoglycemia at the end in each gropu | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Linagliptin, premixedinsulin therapy, peritoneal dialysis, glycemic variability