Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 1 diabetes (BEGIN Basal-Bolus Type 1): a phase 3, randomised, open-label, treat-to-target non-inferiority trial
ABSTRACT Intensive basal-bolus insulin therapy has been shown to improve glycaemic control and reduce the risk of long-term complications that are associated with type 1 diabetes mellitus. Insulin degludec is a new, ultra-longacting basal insulin. We therefore compared the efficacy and safety of insulin degludec and insulin glargine, both administered once daily with mealtime insulin aspart, in basal-bolus therapy for type 1 diabetes.
In an open-label, treat-to-target, non-inferiority trial, undertaken at 79 sites (hospitals and centres) in six countries, adults (aged ≥18 years) with type 1 diabetes (glycated haemoglobin [HbA(1c)] ≤10% [86 mmol/mol]), who had been treated with basal-bolus insulin for at least 1 year, were randomly assigned in a 3:1 ratio, with a computer-generated blocked allocation sequence, to insulin degludec or insulin glargine without stratification by use of a central interactive response system. The primary outcome was non-inferiority of degludec to glargine, assessed as a reduction in HbA(1c) after 52 weeks, with the intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, number NCT00982228.
Of 629 participants, 472 were randomly assigned to insulin degludec and 157 to insulin glargine; all were analysed in their respective treatment groups. At 1 year, HbA(1c) had fallen by 0·40% points (SE 0·03) and 0·39% points (0·07), respectively, with insulin degludec and insulin glargine (estimated treatment difference -0·01% points [95% CI -0·14 to 0·11]; p<0·0001 for non-inferiority testing) and 188 (40%) and 67 (43%) participants achieved a target HbA(1c) of less than 7% (<53 mmol/mol). Rates of overall confirmed hypoglycaemia (plasma glucose <3·1 mmol/L or severe) were similar in the insulin degludec and insulin glargine groups (42·54 vs 40·18 episodes per patient-year of exposure; estimated rate ratio [degludec to glargine] 1·07 [0·89 to 1·28]; p=0·48). The rate of nocturnal confirmed hypoglycaemia was 25% lower with degludec than with glargine (4·41 vs 5·86 episodes per patient-year of exposure; 0·75 [0·59 to 0·96]; p=0·021). Overall serious adverse event rates (14 vs 16 events per 100 patient-years of exposure) were similar for the insulin degludec and insulin glargine groups.
Insulin degludec might be a useful basal insulin for patients with type 1 diabetes because it provides effective glycaemic control while lowering the risk of nocturnal hypoglycaemia, which is a major limitation of insulin therapy.
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ABSTRACT: Many patients with type 2 diabetes continue to have poor glycaemic control and would benefit from insulin therapy. However, resistance to the introduction of insulin therapy can be high on both the part of the healthcare provider and the patient. A number of new, long-acting basal insulins are in development that provide good metabolic control, but with a lower risk of hypoglycaemia than currently available insulins, and greater flexibility in dosing time from day to day. These attributes may address some of the current barriers to insulin initiation and intensification that currently limit the effectiveness of diabetes care.10/2013; DOI:10.1016/j.pcd.2013.09.003
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ABSTRACT: Overview Hypoglycemia is one of the most serious complications associated with glucose-lowering therapy and is a barrier to initiating, intensify-ing, and optimizing therapy, as well as long-term adherence. 1-4 One survey found that, following a mild-to-moderate hypoglycemic epi-sode, 74% of patients with type 1 diabetes mellitus (T1DM) (n = 202) and 43% with type 2 DM (T2DM) (n = 133) modified their insulin dose (FIgurE). 1 Following a severe hypoglycemic episode, 78% and 58% of T1DM and T2DM patients, respectively, modified their insulin dose. 1 The survey also found that two-thirds of patients consumed extra food to avoid a subsequent hypoglycemic episode. The consequences of hypoglycemia are numerous and include diminished patient psycho-logical well-being and quality of life, fear and anxiety, and reduced productivity—the impact being greater following a severe hypogly-cemic episode. 1,2,5-9 For example, 29.9% of patients with T2DM were more fearful that a future hypoglycemic episode would occur follow-ing a mild or moderate hypoglycemic episode compared with 84.2% of patients following a severe hypoglycemic episode. 1 Reports collected from a series of focus groups provide greater insight into the impact of hypoglycemia on the daily lives of patients with T1DM or T2DM (N = 18). 8 The 5 themes that emerged from the results of this study are detailed in TabLE 1. Hypoglycemia is associated with important DM-related out-comes, such as poor glycemic control, likely resulting from modifi-cation and adjustment to the treatment plan. 3,4 Severe symptomatic hypoglycemia was also found to be associated with an increased risk of death in the Action to Control Cardio-vascular Risk in Diabetes (ACCORD) and the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trials. 10,11 In the ADVANCE study, the risk of all-cause mortality was significantly higher in individuals who experienced a severe hypoglycemic episode (blood glu-cose < 50 mg/dL and requiring assistance) compared with those who did not (19.5% vs 9.0%, respectively; hazard ratio [HR], 3.27; 95% confidence interval [CI], 2.29-4.65). In addition, the ADVANCE trial reported that a major macrovascular event (eg, cardiovascular death, nonfatal myocardial infarction, non-fatal stroke) was observed in 16.8% of patients who reported severe hypoglycemia compared with 10.2% of those who did not. The respective rates for a major microvascular event (eg, new or worsening nephropathy, retinopathy) were 11.5% in patients who had experienced a severe hypoglycemic event and 10.1% in those who had not. Other investigations have demonstrated an in-creased risk of dementia in patients who experienced severe hypoglycemia. 12,13 Data from the Kaiser Perman-ente of Northern California registry showed that, com-pared with patients without hypoglycemia, patients with T2DM who had experienced single or multiple episodes of hypoglycemia requiring hospitalization or emergency department care had a graduated in-crease in risk for cognitive impairment: 1 episode (HR, 1.26; 95% CI, 1.10-1.49), 2 episodes (HR, 1.80; 95% CI, 1.37-2.36), and 3 or more episodes (HR, 1.94; 95% CI, 1.42-2.64). 12 Finally, the cost of health care is high-er in patients who experience hypogly-cemia. 9 Moreover, the mean annual cost of hypoglycemia-associated claims for patients treated with human insulin (vial and syringe) was ap-proximately $1500 com-pared with $620 for those treated with in-sulin analogs.
- The Lancet 04/2012; 379(9825):1465-7. DOI:10.1016/S0140-6736(12)60527-3 · 45.22 Impact Factor