A Study on Comparison of Glargine Plus Glulisine With Premixed Insulin in Type 2 Diabetes Patients
Condition: Type2 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

Summary: 
      This study is a multicentre, randomized, open label on comparison of a Long-Acting Basal
      Insulin Analog Glargine plus Glulisine with Premixed Insulin in Adult Patients with Type 2
      Diabetes Mellitus in 200 patients that will be conducted in seven centers in Tamil Nadu. The
      primary outcome measures will be to compare the change in HbA1c from baseline to week 24
      between Glargine OD + Glulisine in comparison with Premixed insulin initiation in insulin
      naïve patients with T2DM. The secondary outcomes is to compare the following in the two arms
      between baseline and 24 weeks Fasting plasma glucose, Postprandial glucose, 7-point
      self-monitored blood glucose (SMBG) profiles, Percentage of participants with HbA1c < 7%,
      Insulin dose, Overall adverse events, Symptomatic Hypoglycemia, Severe hypoglycemic, Weight,
      BMI and Blood pressure.
    

Detailed description: 
      The subjects will be invited to the study centre from the local population who are willing to
      participate in the trial. Each subject will be informed both orally and in writing about the
      study prior to inclusion in the study and only the subjects who give written informed consent
      will be included. The selection of the subjects is based on the inclusion and exclusion
      criteria defined in the protocol. The selected subjects will be given a screening number and
      subjected to screening procedure to find out eligible candidates for enrollment. The
      screening procedure includes obtaining subject's anthropometric data, baseline
      symptomatology, medical history, vital signs, physical examination, laboratory investigations
      like blood glucose (fasting & 2hr after meal), HbA1c, Urea, Creatinine, Liver function test,
      Lipid profile, Urine albumin/creatinine ratio, urine pregnancy (if applicable) and ECG.

      This will be followed by 2 weeks run in period for eligible patients to ensure patients are
      on stable dose of oral therapy and Metformin not < 1500 mg/day. Sulfonylurea will be stopped.

      All the eligible patients as per the inclusion criteria (HbA1c ≥7.5% to ≤ 10.5%, fasting
      blood glucose ≥ 150 mg/dl, and/or Postprandial blood glucose ≥ 200 mg/dl) will be randomized
      in two arms. Participants in arm-1 will receive once daily insulin Glargine (12 units) plus
      once daily Glulisine (4 units) at breakfast/dinner, along with OHAs at stable dose and
      titrated optimally. Participants in the arm-2 will receive once daily premix analogue insulin
      (30/70) 16 units at breakfast/dinner, along with OHAs at stable dose and will be titrated as
      per the treatment algorithm.

      During the randomization visit, the selected subjects after the run in period will be given a
      subject number and randomized between two arms.

      Anthropometric measurements and vital sign will be taken. Concomitant medication and adverse
      events will be noted. Glucose meter, strips, Insulin and study diary will be dispensed.
      Training on Glucose meter usage, hypoglycemia, hyperglycemia symptoms, Insulin injection
      technique and dose titration technique will be done. Subjects will be instructed to maintain
      the record of dosing details in the patient diary. They will be given Diet and Exercise
      counselling. They will be asked to hand over the study diary and Insulin pen (empty or full)
      to the coordinator at each visit.

      First three months will be an insulin dose titration period in which the subjects will be
      asked to visit the clinic at 12 weeks. Telephonic visit at week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10
      and 11. At week 4, and 8 investigator can have an unscheduled visit for training or insulin
      dispensing. During the telephonic visit subjects will be asked about concomitant medication
      and adverse events. During clinic visit at 12 weeks or unscheduled visit at week 4 or 8
      anthropometric measurements, vital signs, concomitant medication and adverse event will be
      recorded. Glucometer strips, Insulin and study diary will be dispensed. The Insulin and study
      diary given during previous visit will be collected. The dose of Insulin will be titrated
      according to the algorithm given in appendix below with the 7 point SMBG done by the subject
      ±5 days before the following weeks 4, 8 & 12 and also insulin dose can be titrated by finger
      prick FBS and PPBS done at week 2, 6 and 10.

      After 3 months, participants in arm-1 may undergo intensification to 2 injections of
      Glulisine if HbA1c is > 7% and/or 2-h postprandial glucose is >140 mg/dL. After 3 months,
      participants in arm-2 premix OD can be made BD if HbA1c is > 7% and/or 2-h postprandial
      glucose is >140 mg/dL despite effective titration of existing doses.

      The next three months will be an insulin dose maintenance period in which the subjects will
      be asked to visit the clinic at 24 week. At week 16 and 20 telephonic visit or an unscheduled
      visit will be performed. During the telephonic visit they will be asked about concomitant
      medication and adverse events. During clinic visit at 24 weeks or unscheduled visit at week
      16 or 20, anthropometric measurements, vital signs, concomitant medication and adverse event
      will be recorded. Glucometer strips, Insulin and study diary will be dispensed. The Insulin
      and study diary given during previous visit will be collected. The dose of Insulin, if needed
      will be titrated according to algorithm given in appendix below with the 7 point SMBG done by
      the subjects ±5 days before the following week 16, week 20 and week 24.

      During the clinic visit at weeks 12 and 24, Medical history, Physical examination, laboratory
      investigations like blood glucose (fasting & 2hr after meal), HbA1c, Urea, Creatinine, Liver
      function test, Lipid profile, Urine albumin/creatinine ratio, urine pregnancy (if applicable)
      and ECG at week 24 will be done.

      During the end of study visit at week 24 the subject will undergo medical examination,
      anthropometric measurements, vital signs, concomitant medication and adverse event will be
      recorded. The Insulin and study diary given during previous visit will be collected.

      Subjects experiencing any hypoglycemia should inform the coordinator or the investigator over
      the phone and make an unscheduled visit. In case they experience adverse event should inform
      the coordinator or the investigator over the phone and make an unscheduled visit as per
      investigator's discretion.
    

Intervention name(s): Glargine + Glulisine; Premixed analogue insulin (70/30)
Intervention type(s): Drug; Drug
Intervention description(s): Glargine should be taken 30 minutes before breakfast/dinner, the dose is adjusted as per fasting blood glucose during each visit and Glulisine should be taken 20 minutes before breakfast/dinner, the dose is adjusted as per postprandial blood glucose during each visit; Premixed analogue insulin should be taken 30 minutes before breakfast/dinner, the dose is adjusted as per fasting blood glucose during each visit.
Other intervention name(s): Lantus + Apidra; Novomix
Intervention MeSH terms: Insulin; Insulin Glargine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment