Titration of basal insulin or immediate addition of rapid acting insulin in patients not at target using basal insulin supported oral antidiabetic treatment - A prospective observational study in 2202 patients.

Aim: Optimal treatment intensification strategies in patients with type-2 diabetes mellitus (T2DM) receiving basal insulin supported oral antidiabetic therapy (BOT) remain controversial. The objective of the present study was to compare outcomes of BOT-intensification by either the uptitration of long-acting insulin glargine or by the immediate addition of a rapid acting insulin analogue (RAIA).

Methods: This was a prospective, observational, 24-week study in T2DM patients with BOT using insulin glargine and baseline glycated hemoglobin (HbA1c) between 7.0 and 8.5%. Patients were stratified by their physicians to one of the following treatment intensification strategies: Basal insulin titration to target with discretionary subsequent addition of RAIA at weeks 12 or 24 (GLAR), or immediate addition of RAIA at baseline (GLARplus).

Results: A total of 3266 patients were prescreened of whom 2202 fulfilled the selection criteria. Of these, 1684 patients were documented in the GLAR group and 518 in the GLARplus group. In the GLAR group, in 91 (5.5%) and 21 patients (1.3%) RAIA was added at weeks 12 and 24, respectively. The groups displayed similar baseline characteristics; except, mean diabetes duration was slightly shorter in the GLAR group (8.7 vs. 9.4 years). During the study, insulin glargine dose was increased from 18.7 to 26.4U (plus 7.7U) in GLAR and from 24.9 to 27.3U (plus 2.4U) in GLARplus patients. Mean RAIA dose was 9.6±4.7U at the final visit. After 24 weeks, HbA1c was reduced by 0.8 and 0.9% in the GLAR and GLARplus groups, respectively (both p<0.001). An HbA1c of ≤7.0% was achieved in 49.2% of GLAR and 48.5% of GLARplus patients. In both groups, we observed improvements in cardiovascular risk factors such as lipids and blood pressure. The rates of symptomatic (1.6 vs. 1.7%) and severe (0.18 vs. 0.19%) hypoglycemic episodes were low and comparable in both groups.

Conclusion: These findings provide evidence that treatment intensification in patients with type 2 diabetes not at glycemic target on BOT with insulin glargine is equally safe and effective using either long-acting insulin titration alone or the addition of a rapid-acting insulin analogue.