Efficacy and Safety Of Different Regimens In Patients With Type 2 Diabetes Receiving Intensive Insulin Therapy

Study Overview
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Brief Summary
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The purpose of this studay is to compare the efficacy of different hypoglycemic regimens versus twice-daily premixed insulin in type 2 diabetes mellitus (T2DM) patients after short-term ntensive Insulin Therapy by using continuous glucose monitoring.

Detailed Description
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This randomized, positive-controlled, open-label, parallel-group study will enroll approximately 78 male and female patients aged 18-70 years with poorly-controlled T2DM (HbA1c >9% or FBS>11.1mmol/L) after short-term intensive insulin therapy. Eligible patients will then be randomized in a 1:1:1 ratio to insulin glargine plus OADs or twice-daily premixed insulin or Insulin Degludec & Liraglutide for 3 months with metformin maintained throughout the study in both treatment groups. All the patients will wear CGM during short-term intensive insulin therapy and after treatment for 7 days. The primary endpoint is plasma glucose change from baseline to month 3. Secondary endpoints include assessment of fasting plasma glucose, total daily insulin dose, hypoglycemia incidence, body weight change, adverse events, and patient satisfaction.

Official Title
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Efficacy and Safety Of Different Hypoglycemic Regimens Compared With Premixed Insulin In Patients With Type 2 Diabetes Receiving Short-term Intensive Insulin Therapy

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: metformin+empagliflozin+insulin glargine
* Drug: IDegLira
* Drug: premixed insulin analogues


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged 18-70 years with poorly-controlled T2DM (World Health Organization diagnostic criteria) BMI 21 32Kg/m2 duration of T2DM more than 1 year FPG≥11.1mmol/L or HbA1c ≥9% for three months fasting C-peptide >1 ng/mL Exclusion Criteria: acute diabetic complications (diabetic ketoacidosis, lactic acidosis, hyperosmolar nonketotic diabetic coma) within the past 1 month; impaired renal function,defined as (but not limited to) serum creatinine levels ≥1.5 mg/dL for males and ≥1.4 mg/dL for females, or the presence of macroproteinuria (> 2 g/day) pregnancy inability to perform self-monitoring of BG (SMBG) acute disease or surgery in the past 3months or preparation for the surgey

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: metformin+empagliflozin+insulin glargine<br>metformin+empagliflozin+insulin glargine | Drug: metformin+empagliflozin+insulin glargine<br>* Randomization was performed with the use of a computer-generated system provided by the sponsor. The dose of metformin will be initiated at 0.5 grams three times a day (the maximum dose is 2g/day); the dose of empagliflozin will be 10 milligrams once a day; insulin glargine will be received once daily at bedtime and the dose will be initiated at the 50% of 0.4-0.5 units/kg/day. All groups received counseling on lifestyle modification.<br>|
| Experimental: IDegLira<br>IDegLira | Drug: IDegLira<br>* Randomization was performed with the use of a computer-generated system provided by the sponsor. Eligible patients will be initiated on 16 units (16 units degludec/0.58 mg liraglutide) and titrated twice weekly. The maximum dose of IDegLira was 50 units (50 units degludec/1.8 mg liraglutide). All groups received counseling on lifestyle modification.<br>|
| Active Comparator: premixed insulin analogues<br>premixed insulin analogues | Drug: premixed insulin analogues<br>* Randomization was performed with the use of a computer-generated system provided by the sponsor. Eligible patients will received twice a day. The total daily insulin dose will be initiated at 0.4-0.5 units/kg/day and adjusted according to the plasma glucose. All groups received counseling on lifestyle modification.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in HbA1c | mean change from baseline in HbA1c after 3-months of treatment. | Month 0 to 3 | 
| Percentage of patients achieving HbA1c <7% | Percentage of patients achieving HbA1c <7% after 3-months of treatment. | Month 0 to 3 | 
| Amplitude of glycemic excursions | Amplitude of glycemic excursions from month 0 to 3 | Month 0 to 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of hypoglycemia incidence | Percentage of hypoglycemia incidence from month 0 to 3 | Month 0 to 3 | 
| Percentage of adverse events | Percentage of adverse events from month 0 to 3 | Month 0 to 3 |