ArticlesInsulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 2 diabetes (BEGIN Basal-Bolus Type 2): a phase 3, randomised, open-label, treat-to-target non-inferiority trial
Introduction
The landmark UK Prospective Diabetes Study (UKPDS)1 showed that, because of unremitting loss of β-cell function that characterises type 2 diabetes mellitus, a substantial number of patients need insulin therapy after 9 years or more of disease. Moreover, many patients need intensification to a basal-bolus insulin regimen after 3–5 years of basal insulin treatment.1 Hypoglycaemia is the main restricting factor in glycaemic management of type 2 diabetes mellitus, leading to physical and psychosocial morbidity and perhaps even mortality.2 Variability in absorption and duration of action and time-action profile peaks associated with administration of subcutaneous insulin can contribute to hypoglycaemia. Therefore, we need an effective basal insulin with a long, flat, and stable profile, and a lowered risk of hypoglycaemia.
Insulin degludec is an ultra-longacting basal insulin in clinical development for the treatment of diabetes. Insulin degludec forms soluble multihexamers on subcutaneous injection, resulting in a depot from which monomers are slowly and continuously absorbed into the circulation. This mechanism leads to the reported ultra-long pharmacokinetic and pharmacodynamic profiles and reduced variability in insulin action compared with insulin glargine.3, 4, 5 A previous proof-of-concept phase 2 clinical trial6 comparing once-daily insulin degludec with insulin glargine in patients with type 2 diabetes mellitus not previously treated with insulin showed similar efficacy and suggested lower rates of hypoglycaemia with insulin degludec. In this phase 3, BEGIN Basal-bolus Type 2 study, we aimed to assess the efficacy and safety of insulin degludec compared with insulin glargine in a basal-bolus regimen in patients with longstanding type 2 diabetes mellitus.
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Trial design and participants
In our phase 3, 52-week, randomised, treat-to-target, parallel-group, open-label, non-inferiority trial, we compared the efficacy and safety of once-daily insulin degludec with once-daily insulin glargine in a basal-bolus regimen with mealtime insulin aspart, with or without metformin, pioglitazone, or both in participants with type 2 diabetes mellitus. We undertook the trial at 123 sites in 12 countries (Bulgaria, Germany, Hong Kong, Ireland, Italy, Romania, Russia, Slovakia, South Africa,
Results
We enrolled and assessed participants between Sept 1, 2009, and Oct 28, 2010. 618 (82%) of 755 participants randomly assigned insulin degludec and 211 (84%) of 251 randomly assigned insulin glargine completed the trial (figure 1). The proportion of participants who withdrew and reasons for withdrawal were similar in the two groups (figure 1).
Demographic and baseline characteristics were very similar between groups and were representative of a population with type 2 diabetes mellitus requiring
Discussion
In participants with advanced insulin-treated type 2 diabetes mellitus, overall glycaemic reductions as measured by HbA1c concentration resulting from basal-bolus intensive insulin therapy with insulin degludec were non-inferior to those noted for insulin glargine, which was to be expected from the treat-to-target trial design.11 Treat-to-target trials allow investigators to minimise potential differences between treatments in measures of plasma glucose and can show differences in safety
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2023, Diabetes Research and Clinical PracticePharmacotherapy of type 2 diabetes: An update and future directions
2022, Metabolism: Clinical and ExperimentalCitation Excerpt :The rate of nocturnal severe hypoglycemia or nocturnal confirmed hypoglycemia (≤3.9 mmol/L) decreased by 15 % (RR 0.85, 95 % CI 0.77–0.92) with Gla-300 compared with Gla-100 [254]. This was confirmed in treat-to-target studies such as the EDITION trials which compared Gla-100 to Gla-300, and the BEGIN study which compared Gla-100 to IDeg [254–258]. Gla-300 and IDeg doses should not be increased more frequently than every 3–4 days [235].
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