Insulin degludec compared with insulin glargine in insulin-naïve patients with type 2 diabetes: A 26-week, randomized, controlled, Pan-Asian, treat-to-target trial

Yukiko Onishi, Yasuhiko Iwamoto, Soon Jib Yoo, Per Clauson, Søren C Tamer, Sungwoo Park, Yukiko Onishi, Yasuhiko Iwamoto, Soon Jib Yoo, Per Clauson, Søren C Tamer, Sungwoo Park

Abstract

Introduction: Insulin degludec (IDeg) is an ultra-long-acting basal insulin with a consistent action profile of >42 h. This trial compared the efficacy and safety of IDeg with insulin glargine (IGlar) in insulin-naïve Asian patients with type 2 diabetes.

Materials and methods: In this multinational, 26-week, open-label, treat-to-target trial, 435 participants (202 females, 233 males; mean age 58.6 years; mean body mass index 25 kg/m(2); mean glycated hemoglobin [HbA1c] 8.5%) were randomized (2:1) to IDeg or IGlar, each administered once daily with ≥1 oral antidiabetic drug(s) (OAD).

Results: After 26 weeks, HbA1c had decreased by 1.24 and 1.35% in the IDeg and IGlar groups, respectively (treatment difference [IDeg - IGlar] 0.11%, 95% confidence interval [CI] -0.03 to 0.24), confirming non-inferiority. Rates of overall confirmed hypoglycemia were similar for IDeg and IGlar during the full trial period (3.0 vs 3.7 episodes/patient-year of exposure [PYE]; rate ratio [RR] 0.82, 95% CI 0.60 to 1.11, P = 0.20), but significantly lower (by 37%) for IDeg during the maintenance period (from week 16 onward; RR 0.63, 95% CI 0.42 to 0.94, P = 0.02). No significant difference in the rate of nocturnal confirmed hypoglycemia was found between IDeg and IGlar in the full trial period (0.8 vs 1.2 episodes/PYE; RR 0.62, 95% CI 0.38 to 1.04, P = 0.07) or maintenance period (RR 0.52, 95% CI 0.27 to 1.00, P = 0.05). Adverse event rates were similar between treatments.

Conclusions: Initiating insulin therapy with IDeg in Asian patients with type 2 diabetes, inadequately controlled with OADs, provides similar improvements in long-term glycemic control to IGlar, but at a significantly lower rate of overall confirmed hypoglycemia once stable glycemic control and insulin dosing are achieved. This trial was registered with www.clinicaltrials.gov (no. NCT01059799).

Keywords: Asian; Insulin degludec; Type 2 diabetes.

Figures

Figure 1
Figure 1
Trial flow diagram. Of the 12 patients in the insulin degludec (IDeg) group who were withdrawn due to ‘withdrawal criteria’, ten patients met withdrawal criterion #3 (‘Major protocol deviation having influence on efficacy or safety data as judged by the investigator’). Of the two remaining patients, one patient was withdrawn due to meeting withdrawal criterion #2 (‘Hypoglycemia during the treatment period posing a safety problem as judged by the investigator’), whereas the other met withdrawal criteria #2 and #3. Of the two patients in the insulin glargine (IGlar) group who were withdrawn due to withdrawal criteria, one patient met withdrawal criterion #3, whereas the other met withdrawal criterion #4 (‘Initiation or significant change of any systemic treatment which in the investigator's opinion could have interfered with glucose metabolism’). %, Proportion of randomized subjects.
Figure 2
Figure 2
Mean (a) glycated hemoglobin (HbA1c) and (b) fasting plasma glucose (FPG) over time. Data are observed mean values for all randomized participants (last observation carried forward is used for each post‐baseline time‐point). Error bars show standard error of the mean. IDeg, insulin degludec; IGlar insulin glargine.
Figure 3
Figure 3
Cumulative number of (a) confirmed hypoglycemic episodes and (b) confirmed nocturnal hypoglycemic episodes. IDeg, insulin degludec; IGlar insulin glargine.

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