Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes: a 1-year, randomized, treat-to-target trial (BEGIN Once Long)

Abstract

Objective: To compare ultra-long-acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs).

Research design and methods: In this 1-year, parallel-group, randomized, open-label, treat-to-target trial, adults with type 2 diabetes with A1C of 7-10% taking OADs were randomized 3:1 to receive once daily degludec or glargine, both with metformin. Insulin was titrated to achieve prebreakfast plasma glucose (PG) of 3.9-4.9 mmol/L. The primary end point was confirmation of noninferiority of degludec to glargine in A1C reduction after 52 weeks in an intent-to-treat analysis.

Results: In all, 1,030 participants (mean age 59 years; baseline A1C 8.2%) were randomized (degludec 773, glargine 257). Reduction in A1C with degludec was similar (noninferior) to that with glargine (1.06 vs. 1.19%), with an estimated treatment difference of degludec to glargine of 0.09% (95% CI -0.04 to 0.22). Overall rates of confirmed hypoglycemia (PG <3.1 mmol/L or severe episodes requiring assistance) were similar, with degludec and glargine at 1.52 versus 1.85 episodes/patient-year of exposure (PYE). There were few episodes of nocturnal confirmed hypoglycemia in the overall population, and these occurred at a lower rate with degludec versus glargine (0.25 vs. 0.39 episodes/PYE; P = 0.038). Similar percentages of patients in both groups achieved A1C levels <7% without hypoglycemia. End-of-trial mean daily insulin doses were 0.59 and 0.60 units/kg for degludec and glargine, respectively. Adverse event rates were similar.

Conclusions: Insulins degludec and glargine administered once daily in combination with OADs provided similar long-term glycemic control in insulin-naive patients with type 2 diabetes, with lower rates of nocturnal hypoglycemia with degludec.

Trial registration: ClinicalTrials.gov NCT00765817.

Figure 1

Glycemic efficacy. A: Mean A1C with time. B: Mean fasting PG with time. C: Nine-point profiles of SMBG at baseline (week 0) and after 52 weeks. Data for the first seven points are obtained on one day and data for the remaining two points are drawn from the next day. Data are reported as the mean ± SEM. Missing data after baseline were imputed with the last observation carried forward approach. Ideg, insulin degludec; IGlar, insulin glargine; od, once daily.

Figure 2

Confirmed hypoglycemic episodes. A: Overall confirmed hypoglycemic episodes. B: Nocturnal confirmed hypoglycemic episodes. See methodology for plotting graph in the Supplementary Data online. IDeg, insulin degludec; IGlar, insulin glargine; od, once daily.