Does serum 1,5-anhydroglucitol establish a relationship between improvements in HbA1c and postprandial glucose excursions? Supportive evidence utilizing the differential effects between biphasic insulin aspart 30 and insulin glargine.

AIM: To investigate the relationship between changes in glycated haemoglobin (HbA(1c)) and postprandial glucose excursions on 1,5-anhydroglucitol (1,5-AG) in patients with Type 2 diabetes, utilizing the differential effects between biphasic insulin aspart 30 (BIAsp 30) or insulin glargine (IGlar) on postprandial glucose (PPG) levels. METHODS: 1,5-AG was measured using the GlycoMark assay at baseline and after 12 and 28 weeks in the INITiation of Insulin to reach HbA(1c) Target (INITIATE) study of 233 patients randomized to either BIAsp 30 or IGlar. RESULTS: Baseline 1,5-AG was low and not significantly different (4.9 +/- 3.5 and 4.3 +/- 2.6 microg/ml in the BIAsp 30 and IGlar groups, respectively). After 28 weeks, the levels of 1,5-AG were higher in the BIAsp 30 than in the IGlar group (13.4 vs. 11.1 microg/ml, P = 0.008) and change from baseline was 25% greater with BIAsp 30 than IGlar (8.4 vs. 6.7 microg/ml, P = 0.011). 1,5-AG levels increased as a function of decreasing HbA(1c) or the average change in postprandial plasma glucose (PPG(ave)) with significant relationships for 1,5-AG/ HbA(1c) vs. HbA(1c) or 1,5-AG/PPG(ave )vs. PPG(ave) (both P < 0.0001), respectively. CONCLUSIONS: As reported in previous publications, 1,5-AG reflects ambient glycaemic control and increases with reductions in HbA(1c) and postprandial glucose. The greater reductions in postprandial excursion achieved with BiAsp 30 compared with glargine were associated with greater increases in 1,5-AG. Even moderate elevations in HbA(1c) substantially lower 1,5-AG, suggesting that it can be most discriminating in identifying patients with excessive postprandial glucose excursions at HbA(1c) levels that approach the upper end of the normal range.

Combination therapy for type 2 diabetes: repaglinide plus rosiglitazone.

AIMS: This 24-week, randomized, multicentre, open-label, parallel-group clinical trial compared efficacy and safety of repaglinide monotherapy, rosiglitazone monotherapy, and combination therapy (repaglinide plus rosiglitazone) in Type 2 diabetes after unsatisfactory response to sulphonylurea or metformin monotherapy. METHODS: Enrolled patients (n = 252) were adults having Type 2 diabetes for at least 1 year, with HbA(1c) values > 7.0% after previous monotherapy (sulphonylurea or metformin, >/= 50% maximal dose). Prior therapy was withdrawn for 2 weeks, followed by randomization to repaglinide, rosiglitazone, or repaglinide/rosiglitazone. Study treatments were initiated with a 12-week dose optimization period (doses optimized according to labelling), followed by a 12-week maintenance period. Efficacy endpoints were changes in HbA(1c) values (primary) or fasting plasma glucose values (secondary). RESULTS: Baseline HbA(1c) values were comparable (9.3% for repaglinide, 9.0% for rosiglitazone, 9.1% for combination). Mean changes in HbA(1c) values at the end of treatment were greater for repaglinide/rosiglitazone therapy (-1.43%) than for repaglinide (-0.17%) or rosiglitazone (-0.56%) monotherapy. Reductions of fasting plasma glucose values were also greater for combination therapy (-5.2 mmol/l, -94 mg/dl) than for repaglinide monotherapy (-3.0 mmol/l, -54 mg/dl) or rosiglitazone monotherapy (-3.7 mmol/l, -67 mg/dl). Minor hypoglycaemic events occurred in 9% of combination therapy patients, vs. 6% for repaglinide and 2% for rosiglitazone. Individual weight gains for combination therapy were correlated to HbA(1c) response. CONCLUSIONS: The combination therapy regimen was well tolerated. In patients previously showing unsatisfactory response to oral monotherapy, glycaemic reductions were greater for the repaglinide/rosiglitazone combination regimen than for use of either repaglinide or rosiglitazone alone.