Insulin degludec once-daily in type 2 diabetes: simple or step-wise titration (BEGIN: once simple use)

Athena Philis-Tsimikas, Meryl Brod, Marcus Niemeyer, Ann Marie Ocampo Francisco, Jeffrey Rothman, Athena Philis-Tsimikas, Meryl Brod, Marcus Niemeyer, Ann Marie Ocampo Francisco, Jeffrey Rothman

Abstract

Introduction: Insulin degludec (IDeg) is a new basal insulin in development with a flat, ultra-long action profile that may permit dosing using a simplified titration algorithm with less frequent self-measured blood glucose (SMBG) measurements and more simplified titration steps than currently available basal insulins.

Methods: This 26-week, multi-center, open-label, randomized, treat-to-target study compared the efficacy and safety of IDeg administered once-daily in combination with metformin in insulin-naïve subjects with type 2 diabetes using two different patient-driven titration algorithms: a "Simple" algorithm, with dose adjustments based on one pre-breakfast SMBG measurement (n = 111) versus a "Step-wise" algorithm, with adjustments based on three consecutive pre-breakfast SMBG values (n = 111). IDeg was administered using the FlexTouch® insulin pen (Novo Nordisk A/S, Bagsværd, Denmark), with once-weekly dose titration in both groups.

Results: Glycosylated hemoglobin (HbA1c) decreased from baseline to week 26 in both groups (-1.09%, IDegSimple; -0.93%, IDegStep-wise). IDegSimple was non-inferior to IDegStep-wise in lowering HbA1c [estimated treatment difference (IDegSimple - IDegStep-wise): -0.16% points (-0.39; 0.07)95% CI]. Fasting plasma glucose was reduced (-3.27 mmol/L, IDegSimple; -2.68 mmol/L, IDegStep-wise) with no significant difference between groups. Rates of confirmed hypoglycemia [1.60, IDegSimple; 1.17, IDegStep-wise events/patient year of exposure (PYE)] and nocturnal confirmed hypoglycemia (0.21, IDegSimple; 0.10, IDegStep-wise events/PYE) were low, with no significant differences between groups. Daily insulin dose after 26 weeks was 0.61 U/kg (IDegSimple) and 0.50 U/kg (IDegStep-wise). No significant difference in weight change was seen between groups by week 26 (+1.6 kg, IDegSimple; +1.1 kg, IDegStep-wise), and there were no clinically relevant differences in adverse event profiles.

Conclusion: IDeg was effective and well tolerated using either the Simple or Step-wise titration algorithm. While selection of an algorithm must be based on individual patient characteristics and goals, the ability to attain good glycemic control using a simplified titration algorithm may enable patient empowerment through self-titration, improved convenience, and reduced costs.

Trial registration: ClinicalTrials.gov NCT01326026.

Figures

Fig. 1
Fig. 1
BEGIN Once Simple participant flow. *IDegSimple: arthralgia and blurred vision (1 subject); toxicity to various agents (1 subject); astrocytoma (1 subject); acute myocardial infarction (1 subject). IDegStep-wise: liver metastases (1 subject); intervertebral disc protrusion (1 subject); worsening of type 2 diabetes/vitamin D deficiency/anterior pituitary disorder/depression (1 subject). †IDegSimple: withdrawal of consent (2 subjects), investigator decision to withdraw subject due to safety or non-compliance (2 subjects), randomized in error (1 subject). IDegStep-wise: withdrawal of consent (2 subjects), investigator decision to withdraw subject due to safety or non-compliance (1 subject), randomized in error (4 subjects). ‡IDegSimple: lost to follow-up (2 subjects) and withdrawn after 11.7 weeks of treatment due to HbA1c increased (1 subject) IDegStep-wise: lost to follow-up (3 subjects). AE adverse event, FAS full analysis set, IDeg insulin degludec, SAS safety analysis set
Fig. 2
Fig. 2
BEGIN Once Simple glycemic efficacy: a mean HbA1c over time; b mean FPG ± SEM over time; c 8-point SMBG profile at baseline and week 26. BF breakfast, FAS full analysis set, FPG fasting plasma glucose, IDeg insulin degludec, HbA1c glycosylated hemoglobin, SEM standard error of the mean, SMBG self-measured blood glucose
Fig. 3
Fig. 3
Hypoglycemia rate (IDeg) in the BEGIN Type 2 diabetes trials: a confirmed hypoglycemia, b nocturnal confirmed hypoglycemia. Data from this trial shown by light blue bars. Rate (events/patient year of exposure) is at end-of-trial and based on SAS. IDeg insulin degludec, PYE patient year of exposure, SAS statistical analysis set

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Source: PubMed

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