Multi-Center Study Comparing Efficacy and Safety of Frequently Modified Insulin Therapy

Prospective, Open-Label, Randomized, Controlled, Multi-Center Study Comparing Efficacy and Safety of Frequently Modified Insulin Therapy Using Dosage Recommending Device

Hygieia Research seeks to conduct a prospective randomized clinical study involving adult subjects with uncontrolled Type-2 diabetes requiring insulin. The study seeks to demonstrate that the clinical application of the d-Nav will achieve metabolic control in a safe and effective manner.

The purpose of this study is to demonstrate that the use of d-Nav (d-Nav group) is superior to titration of insulin dosage relying on data from glucose meters with health care provider support (Control) in the management of insulin treated diabetes, by randomizing 200 insulin treated subjects with type 2 diabetes.

Primary Objective: To demonstrate a greater reduction in HbA1c at 6-months for d-Nav users compared to control patients in the primary cohort.

Inclusion Criteria:

1. 21 to 70 years of age

2. If female, must be of non-childbearing potential or have a negative urine pregnancy test at screening and using adequate method of contraception throughout conduct of the study

3. Clinical diagnosis of Type-2 diabetes for at least 1-year

4. HbA1c 7.5% to 11% inclusive

5. Total daily dose of insulin of 25 units or more (10 units if on Lantus® alone) using one of these insulin regimens:

   • Regimen 1 - a single injection of the long-acting insulin analog Lantus® (Glargine) per day (limited to a daily dose that is no more than 0.7 units per kg of body weight);
   • Regimen 2 - twice daily biphasic insulin (i.e., Humalog® Mix 75/25, NovoLog® Mix 70/30) or pre-mixed insulin (i.e., Humulin® 70/30, Novolin® 70/30);
   • Regimen 3 - a short-acting insulin analog (i.e., Humalog®-Lispro, NovoLog®-Aspart, Apidra®-Glulisine) before each meal and are treated with a single injection of the long-acting insulin analog Lantus® (Glargine) per day and do not utilize an insulin/carbohydrate ratio for calculating their short-acting insulin doses; or
   • Regimen 4 - with a short-acting insulin analog (i.e., Humalog®-Lispro, NovoLog®-Aspart, Apidra®-Glulisine) before each meal and a single injection of the long-acting insulin analog Lantus® (Glargine) per day and utilize an insulin/carbohydrate ratio for calculating their short-acting insulin doses.

6. On same insulin regimen for the previous 3-months

7. May be using other diabetes agents at a stable dose for the last 3-months

8. Signed and dated informed consent document, which contains HIPAA waiver information informing about all of the aspects of the clinical study;

9. Will regularly conduct Self-Monitored Blood Glucose. Prior to randomization must meet the following .

   Minimum number of tests required from all subjects:

   • Basal insulin subjects at least 4 fasting glucose readings/wk
   • Premixed insulin subjects at least 8 readings/wk
   • Basal-bolus insulin therapy subjects at least 16 total readings/wk

10. Willing and able to comply with the scheduled clinical study activities and glucose testing:

    • Basal insulin subjects at least 5 fasting glucose readings/wk
    • Premixed insulin subjects at least 5 pre-breakfast and 5 pre-evening meal readings/wk
    • Basal-bolus insulin therapy subjects at least 20 total readings/wk which include 5 readings before each of the following time points: breakfast, lunch, evening meal and bedtime.

    Note: All subjects may be asked to test during the night if clinically indicated.

11. Participant must have a primary care provider

Exclusion Criteria:

1. History >2 episodes of severe hypoglycemia (see definition below) in the past year, or hypoglycemic unawareness when glucose levels are ≤ 50 mg/dl;
2. Significant physical, psychological, or cognitive impairment that would prohibit adherence to the protocol at the discretion of the PI;
3. Splitting Lantus and taking Lantus twice a day
4. Severe cardiovascular disease including a history of congestive heart failure, unstable angina, myocardial infarction or stroke within the 6-months preceding enrollment;
5. Active anemia w/ hematocrit ≤ 25% in women or 30% in men;
6. Advanced kidney disease Stage 4 (eGFR < 30 ml/min) and above
7. Active cancer or cancer in the past 2-years (except non-melanoma skin cancer)
8. History of significant liver disease including cirrhosis or elevated liver enzymes (e.g., AST and ALT greater than 3 times the upper limit of normal values).
9. BMI > 45 kg/m2
10. Are pregnant, plan to become pregnant during the study period, or are breastfeeding.
11. Have a BGMS that cannot be downloaded.