Basal‐prandial versus premixed insulin in patients with type 2 diabetes requiring insulin intensification after basal insulin optimization: A 24‐week randomized non‐inferiority trial

Abstract

Background: The aim of the present 24-week multicentre randomized noninferiority trial was to compare the efficacy and safety of two insulin intensification strategies in uncontrolled type 2 diabetes despite optimized basal insulin therapy. Methods: Patients with fasting plasma glucose (FPG) <130 mg/dL and HbA1c 7.0%-10.0% while on insulin glargine were randomized to a basalprandial group (stepwise addition of insulin glulisine) or a premixed insulin group (insulin aspart/insulin aspart protamine 30/70 starting with 6 IU twice daily). The primary endpoint was the change in HbA1c after 24 weeks (noninferiority margin 0.4%). Results: At Week 24, the adjusted mean change from baseline HbA1c was -0.94 ± 0.09% and -1.04 ± 0.09% in basal-prandial and premixed insulin groups, respectively, with a mean difference of -0.09% (95% confidence interval [CI] -0.35, 0.16). A lower rate of hypoglycemia with a similar reduction in HbA1c was observed during stabilization of the total daily insulin dose in the premixed insulin group (Weeks 0-12). After stabilization of the total daily insulin dose, the rate of hypoglycemia and the total daily insulin dose were similar in the two groups. Conclusions: The efficacy and safety of the two intensifying regimens were similar after stabilization of the total daily insulin dose when oral agents were maintained. Starting with a lower total daily insulin dose with a gradual change in the treatment regimen was helpful in reducing the rate of hypoglycemia during initial stabilization of the total daily insulin dose.

Initiation and Intensification Strategies in Type 2 Diabetes Management: A Comparison of Basal Plus and Premix Regimens

“…Prandial insulin glulisine was administered OD in 50% of patients and BID in the remaining 50%. With regard to HbA1c, similar reductions from baseline were observed in both insulin glargine OD + insulin glulisine (OD or BID) and premix BID regimens, along with the proportion of patients achieving HbA1c <7% (<53 mmol/mol) [29]. …”

“…Three published trials ( n  = 970) have directly compared basal plus and premix regimens in patients with T2D uncontrolled with basal insulin OD plus OADs [29–31] (Table 2). Sponsored by Sanofi, Jin et al [29] [NCT01212913] had an initial 12-week period whereby insulin was titrated to stabilize insulin doses in both treatment arms, resulting in insulin doses being similar in both arms from week 12 onwards.…”

“…Sponsored by Sanofi, Jin et al [29] [NCT01212913] had an initial 12-week period whereby insulin was titrated to stabilize insulin doses in both treatment arms, resulting in insulin doses being similar in both arms from week 12 onwards. Sponsored by Eli Lilly, patients in the Tinahones et al [30] trial [NCT01175824] underwent a 2-week screening period, after which they were randomized to treatment.…”

“…Jin et al assessed intensification with basal plus (insulin glargine OD + insulin glulisine [OD or BID]) and premix BID in Korean patients with T2D [29]. This study is of interest as there may be differences in the general context of the typically high-carbohydrate diet and known insulin secretory deficits that characterize Asian T2D [32].…”

“…A lower daily insulin dose in the premix BID arm compared with the basal plus arm was initially observed in the Jin et al [29] trial, but this was gradually up-titrated, such that end of trial insulin dose was similar in both regimens. Tinahones et al [30] did not report a significant difference in mean insulin dose at end of trial between basal plus and premix regimens (50.8 vs. 53.1 U, respectively).…”