Improving Glycaemic Control in Malaysian Patients With Type 2 Diabetes Mellitus With Insulin Pump Therapy
Improving Glycaemic Control in Malaysian Patients With Type 2 Diabetes Mellitus With Insulin Pump Therapy
The purpose of this study is to evaluate the comparative efficacy of insulin pump therapy
 versus multiple daily injections in insulin-taking type 2 diabetes mellitus who are
 sub-optimally controlled with premixed insulin regimen. This research is necessary because
 many patients with type 2 diabetes mellitus do not meet their glucose targets.

 In advanced Type 2 diabetes mellitus, many patients develop worsening diabetes control and
 unable to reach the glucose targets despite intensive insulin regimens.This is further
 complicated by the risks of low blood sugar and weight gain. These limitations of multiple
 daily injection treatment show the need for new treatments for this group of patients.
This study evaluates between group change in glycemic control (HbA1c) after 6 months of
 insulin pump therapy in patients with type 2 Diabetes Mellitus, as compared to patients on
 multiple daily injections (MDI) therapy over the same time period. It also evaluates between
 group changes in diabetes clinical outcomes after 6 months in patients with type 2 DM.
 Patient related outcomes will be measured after 6 months of therapy. The primary endpoint
 will be between group difference in average HbA1c changes from baseline to 6 months, when
 comparing Continuous Subcutaneous Insulin Infusion (CSII) to MDI.

 The secondary end point concerns the safety issues such as severe hypoglycemia incidence:
 defined as an episode absolutely requiring assistance from another person and preferably
 accompanied by a confirmatory blood glucose by finger stick of less than 50mg/dL (2.8
 mmol/L), (i.e., subject is unable to treat self and requires carbohydrate, glucagon or other
 resuscitative actions to prevent further clinical deterioration), hospitalizations, Diabetic
 Ketoacidosis (DKA), an acute metabolic complication of diabetes, characterized by
 hyperglycemia, hyperketonemia, and metabolic acidosis, within group difference in HbA1c from
 6 months to 12 months, change in weight or BMI, change in Lipids : total cholesterol, high
 density lipoprotein(HDL),low density lipoprotein(LDL),triglyceride, change in blood pressure,
 Insulin Dosage Changes (Total Daily Dose), Number of self monitoring blood glucose
 (SMBG)/day, treatment satisfaction: Diabetes Treatment Satisfaction Questionnaire status and
 change version (DTSQs and DTSQc).

 The hypotheses underlying the secondary outcomes : the pump therapy improves glycaemic
 control whilst utilizing less total daily dose of insulin in comparison to multiple daily
 injections of insulin. This is associated with parallel improvement in metabolic profiles
 such as blood pressure and lipids. As for the glucose monitoring, investigators want to
 evaluate whether there is any difference in the frequency of SMBG/day between the 2 treatment
 groups. More frequent SMBG monitoring denotes better compliance, motivation and empowerment
 by the participants to control their diabetes.
Inclusion Criteria:

 CRITERIA FOR INCLUSION AT SCREENING

 1. Diagnosed with type 2 Diabetes Mellitus, as per Investigator diagnosis

 2. HbA1c (DCCT-standard) must be ≥ 9.0% and ≤12%

 3. Insulin resistance defined as required daily dose up to 1.5u/kg or a maximum of 200
 units insulin per day

 4. Aged 20 to 75 years old inclusive

 5. On premixed regimen (human or analogue insulin) defined as ≥ 2 injections per day for
 at least 3 months prior signing the informed consent

 6. Ability to comply with technology, according to Investigator's judgment

 7. Patients must be willing to undergo all study procedures

 8. Female patients of child-bearing potential must be using adequate contraception means
 as assessed by Investigator

 CRITERIA FOR INCLUSION AT RANDOMISATION

 1. Diagnosed with type 2 DM, as per Investigator diagnosis

 2. HbA1c (DCCT-standard) must be ≥ 9.0% and ≤12%

 3. Insulin resistance defined as required daily dose up to 1.5 U/Kg or a maximum of 200
 units per day

 4. On premixed regimen (human or analogue insulin) defined as ≥ 2 injections per day for
 at least 3 months prior signing the informed consent

 5. Ability to comply with technology, according to Investigator's judgment

 6. ≥ 2.5 SMBG per day on average

 7. Patients must be willing to undergo all study procedures

 8. Female patients of child-bearing potential must be using adequate contraception means
 as assessed by Investigator

 Exclusion Criteria:

 CRITERIA FOR EXCLUSION (AT SCREENING AND RANDOMISATION)

 1. Subject has a history (≥ 2 events) of hypoglycemic seizure or hypoglycemic coma within
 the last 6 months

 2. Subject is pregnant as assessed by a pregnancy test with central laboratory, or plans
 to become pregnant during the course of the study

 3. Participation in another interventional clinical study, on-going or completed less
 than 3 months prior to signature of Patient Informed Consent.

 4. Subject has proliferative retinopathy or sight threatening maculopathy

 5. Subject has

 -  an acute coronary syndrome (myocardial infarction or unstable angina) within 12
 months OR

 -  coronary artery revascularization by bypass surgery or stenting within 3 months
 OR

 -  a transient ischemic attack (TIA) or cerebrovascular accident (CVA) within 3
 months OR

 -  hospitalization for heart failure within 3 months or current New York Functional
 Class III or IV OR

 -  current 2nd or 3rd degree heart block OR

 -  symptomatic ventricular rhythm disturbances OR

 -  thromboembolic disease within the last 3 months OR

 6. Subject with renal impairment expressed as estimated glomerular filtration rate (eGFR)
 using the Modification of Diet in Renal Disease (MDRD) formula < 30 ml/min as
 demonstrated by the screening central laboratory value at the time of enrollment

 7. Subject has taken oral or injectable steroids within the last 30 days.

 8. Systolic blood pressure on screening visit is > 180 mmHg

 9. Diastolic blood pressure on screening visit is > 110 mmHg

 10. Any other disease (eg active cancer under treatment) or condition including
 abnormalities found on the screening tests, that in the opinion of the Investigator,
 may preclude the patient from participating in the study

 11. Taking any medication prescribed for weight loss

 12. Alcohol or drug abuse, other than nicotine, at the Investigator's discretion Use of a
 Glucagon Like Peptide-1 agonist or pramlintide (Symlin®). Glucagon Like Peptide-1
 slows gastric emptying, thereby decreasing the rate of glucose absorption. Pramlintide
 (Symlin®) is a commercially available analogue of amylin, a synergistic partner to
 insulin.