Once-daily initiation with biphasic insulin aspart 30 versus insulin glargine in patients with type 2 diabetes inadequately controlled with oral drugs: an open-label, multinational RCT

Abstract

Objectives:

To assess the efficacy and safety of biphasic insulin aspart 70/30 (BIAsp 30) and insulin glargine, administered once daily in subjects with type 2 diabetes inadequately controlled with oral anti-diabetic drugs.

Research design and methods:

In this 26-week, open-labeled, randomized, parallel-group, multinational, treat-to-target trial, 480 insulin-naïve subjects were randomized to receive either BIAsp 30 before dinner or insulin glargine at bedtime, both in combination with metformin and glimepiride.

Trial registration:

NCT00469092, ClinicalTrials.gov.

Results:

A total of 433 subjects completed the trial. Estimated mean reduction in HbA_1c from baseline to end of treatment was −1.41% with BIAsp 30 and −1.25% with insulin glargine (BIAsp 30 – insulin glargine = −0.16%, 95% CI [−0.30; −0.02], p = 0.029). At the end of treatment, mean HbA_1c was 7.1% and 7.3% for BIAsp 30 and insulin glargine, respectively. Significantly lower plasma glucose levels were observed with BIAsp 30 post-dinner (BIAsp 30 – insulin glargine = −0.52 mmol/L, 95% CI [−1.02; −0.03], p = 0.04) and at bedtime (BIAsp 30 – insulin glargine = −0.78 mmol/L, 95% CI [−1.25; −0.31], p < 0.01). The relative risk (RR) of experiencing a nocturnal hypoglycemic episode (00:00–06.00 a.m.) was significantly higher with BIAsp 30 than with insulin glargine (1.1 versus 0.5 episodes/year, RR = 2.41, 95% CI [1.34; 4.34], p = 0.003), but overall hypoglycemia rates were low. There were three major hypoglycemic episodes in each group.

Conclusions:

With respect to HbA_1c, BIAsp 30 fulfilled the statistical criteria for non-inferiority and superiority to insulin glargine and, according to pre-defined criteria, the improvements in HbA_1c are considered clinically equivalent. Subjects had an increased risk of minor nocturnal hypoglycemia with BIAsp 30. There were no differences in treatment satisfaction between the two groups.

Key words::

• Biphasic insulin aspart
• Glycemic control
• Hypoglycemia
• Insulin glargine
• Once-daily
• Type 2 diabetes

Transparency

Declaration of funding

The trial was financially supported by Novo Nordisk A/S.

Declaration of financial/other relationships

K.S. has disclosed receiving honoraria for speaking engagements, participation in advisory boards and participation in clinical trials from the following companies: Eli Lilly, Novo Nordisk, Sanofi–Aventis, Servier, Bristol–Myers Squibb, Roche Diagnostics, Bioton (Poland), Merck, AstraZeneca, GlaxoSmithKline, Takeda and Novartis. W.B. has disclosed receiving honoraria from Novo Nordisk, AstraZeneca and Sanofi–Aventis for conducting clinical trials, and speaker fees from MSD and Bayer. S.K. has disclosed receiving speaker fees from Eli Lilly. Henrik F. Thomsen is currently employed by Novo Nordisk A/S. Milica Pesic has disclosed receiving honoraria from the Novo Nordisk (Beograd) (for speaking engagements) and from Sanofi–Aventis, Serbia (local educational meetings). D.T.K. and A.S. have disclosed that they have no relevant financial relationships.

Acknowledgments

Appreciation is given to all investigators who contributed to the trial. Furthermore, the authors wish to thank Julie Clyde, PhD, Merete Pedersen, PhD, and Paul Drake, PhD (all Novo Nordisk A/S) who provided medical writing services on behalf of Novo Nordisk A/S.

Notes

* Novolog and NovoMix are registered trade names of Novo Nordisk A/S, Bagsværd, Denmark.

† Lantus is a registered trade name of Sanofi–Aventis, Paris, France.