The efficacy of glycemic control in type 1 diabetic patients with either once- or twice-daily glargine insulin injection was evaluated in this long-term, prospective, nonrandomized study. Eighty-two type 1 diabetic patients were followed over 12–15 months after conversion from a single bedtime NPH insulin injection to a single bedtime insulin glargine injection. These patients were switched with the availability of glargine insulin to reduce frequency and severity of nocturnal hypoglycemia and to improve fasting glucose levels. This group of type 1 diabetic patients was switched to glargine insulin in place of twice-daily NPH. These patients continued their same bolus therapy with either insulin lispro or aspart and underwent frequent (three to five times daily) home glucose monitoring. This study showed the expected fewer nocturnal hypoglycemic events, but the primary outcome was an improvement in glycemic control based on the HbA1c values. Patients HbA1c values were determined every 8 weeks, and insulin doses were titrated, with glargine adjusted based on morning fasting glucose values. If the HbA1c remained above goal, the intensity of home glucose monitoring was increased and bolus therapy was adjusted accordingly. In one-quarter of patients, the lunch bolus titration resulted in mid-afternoon hypoglycemia, and when reduced, the patients had elevated presupper glucose values. Patients who had an increase in their HbA1c and/or persistent elevation of presupper glucose despite titration of both bolus insulin and glargine insulin were then placed on twice-daily glargine injections. A spilt dose of glargine was given only after titration of glargine insulin resulted in morning hypoglycemia and/or persistent elevation of the afternoon blood glucoses that could not be corrected with bolus titration.
Sixty-two subjects were using glargine insulin once daily, and the remaining 20 (24.2%) subjects required twice-daily therapy. The 24.2% of patients on split glargine were converted from once-daily glargine injections after an average of 289 ± 203 days (median 259). At that time, their HbA1c had deteriorated from an initial value of 7.9 ± 1.5 to 8.1 ± 1.4% (P = 0.16) and titration was limited by the symptoms outlined above. Subjects on split glargine did not differ from those subjects using once-daily glargine injections in regard to their age (P = 0.21), duration of diabetes (P = 0.21), baseline HbA1c (P = 0.91), presence of detectable C-peptide (P = 0.78), or the presence of microvascular complications: retinopathy (P = 0.37), nephropathy (P = 0.44), neuropathy (P = 0.30), or macrovascular complications (P = 0.88).
In the single-daily injection patients, the HbA1c improved significantly (from 7.8 to 7.3%, P = 0.01) after 476 ± 178 days on glargine insulin. The split glargine injection subjects also had an improvement in the HbA1c from 7.9 to 7.4% (P = 0.03) over a 3- to 6-month period. The ending HbA1c between groups was not significant (P = 0.80). The decrease from the mean starting HbA1c was identical between groups; however, a more significant drop in the HbA1c from the time of spilt to the end of the study (8.1 to 7.4%) did reach statistical significance (P = 0.001). To achieve this improved glycemic control in these patients, 70% more glargine was required (44 ± 26 vs. 26 ± 13 units, P > 0.008).
In conclusion, in this prospective, nonblinded, nonrandomized, prospective study, one-quarter of type 1 diabetic patients required twice-daily glargine insulin injections to achieve acceptable glycemic control. The reason for this was that more glargine insulin could be safely and/or effectively used when split in this population. Regardless, type 1 diabetic patients on glargine insulin improved their glycemic control, as measured by the HbA1c values. Patients who do not achieve control after a titration period should receive split daily doses to achieve glycemic control.
This is the first study to demonstrate an improvement in HbA1c in type 1 diabetic subjects using basal-bolus therapy after conversion from basal NPH insulin to basal glargine insulin. Previous studies were not continued beyond 6 months, and the protocols restricted glargine to once-daily dosing (1–3). Using our study data to project the outcome, if all patients remained on single daily dosing, then the average HbA1c reduction would have been 0.3%, which is similar to other studies, and would not have been statistically significant.