HbA1c Variability in Type II Diabetes

What this study is testing ClinicalTrials.gov NCT02879409 ↗

Description as written by the study sponsor.

There are numerous possible reasons why it could be speculated that HbA1c variability may affect complication risk. Of interest are the concepts that both laboratory and clinic evidence suggests that periods of sustained hyperglycemia are 'remembered' (metabolic memory), this in turn is recognized to place patients at greater long-term risk of complications. As such it can be speculated that the detrimental effect of variability in HbA1c may be mediated via the same mechanism as 'metabolic memory' phenomenon. Aims: To determine whether treatment to one of 2 threshold levels will result in one group of type 2 diabetes patients having the same mean HbA1c but with differing HbA1c variability to that of another and related to markers of oxidative stress, inflammation and microvascular complications. To determine whether a difference in HbA1c variability between the 2 groups will reflect in changes in small nerve fibers assessed with the sensitive method of corneal confocal microscopy and cardiac autonomic function testing. To assess the reproducibility of HbA1c measurement from a whole blood samples initially analyzed and then stored at -80C until the end of the study (2-3 years), as well as storing an aliquot of haemolysate, for reanalysis at the end of the study. In one arm the investigators will intensify treatment in those with FPG\>140mg/dl until their FPG is \<90mg/dl, using whatever treatment is clinically appropriate for them, and only intensify it further if their FPG rises to \>140mg/dl again. In the other group the investigators will intensify if their FPG is \>115 mg/dl until it is \<=115 mg/dl and intensify further if \>115 mg/dl again. A total of 20 visits within a time frame of 2 and half years will be performed. Visits procedures will include routine biochemistry, eGFR, lipids, fasting glucose, insulin and full blood count, HbA1c, SHBG, hsCRP. EPIC and G-PAQ questionnaires will be collected. Autonomic function testing using deep breathing heart rate variability, and a sensitive measure of small fiber neuropathy using corneal confocal microscopy and a 24 hour urine collection for urinary isoprostanes to measure oxidative stress will be performed, at baseline, 12 and 24 months.

Treatments tested

• Metformin also known as Glucophage Drug

  Initial: 500 mg once daily; dosage may be increased by 500 mg weekly; maximum dose: 2,000 mg once daily

• Gliclazide also known as Diamicron, Diamicron MR Drug

  There is no fixed-dosage regimen for the management of diabetes mellitus with gliclazide. Dose will be individualized based on frequent determinations of blood glucose during dose titration and throughout maintenance. The 30 mg modified-release tablet equals the 80 mg immediate-release tablet. Immediate-release tablet: Initial: 80 mg twice daily; titrate based on blood glucose levels. Usual dosage range: 80 to 320 mg/day (maximum dose: 320 mg/day); dosage of ≥160 mg should be divided into 2 equal parts for twice-daily administration. Modified-release tablet: Initial: 30 mg once daily; titrate in 30 mg increments every 2 weeks based on blood glucose levels. Maximum dose: 120 mg once daily

• Sitagliptin also known as Januvia Drug

  Oral: 100 mg once daily

• Liraglutide also known as Victoza Drug

  SubQ: Initial: 0.6 mg once daily for 1 week; then increase to 1.2 mg once daily; may increase further to 1.8 mg once daily if optimal glycemic response not achieved with 1.2 mg daily.

• Pioglitazone also known as Actos Drug

  Oral, Monotherapy or combination therapy: 15-30 mg once daily Patients with heart failure (NYHA Class I or II): Monotherapy or combination therapy: 15 mg once daily

• Dapagliflozin also known as Forxiga, Farxiga Drug

  5mg once daily increasing to 10mg once daily as required

• human insulin also known as novorapid, glargine Drug

  insulin dosage and administration according to physician