Superior HbA1c control with the fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with a maximum dose of 50 units of insulin degludec in Japanese individuals with type 2 diabetes in a phase 3, double-blind, randomized trial

Abstract

Aims: To investigate the efficacy and safety of insulin degludec/liraglutide (IDegLira) compared with 50 U insulin degludec (degludec) or less in Japanese individuals with type 2 diabetes (T2D).

Materials and methods: In this 26-week, double-blind, multicentre, treat-to-target trial, Japanese individuals with T2D that was uncontrolled with basal or pre-mix insulin (20-50 units) were randomized (1:1) to receive IDegLira or degludec, both with metformin. The maximum dose was 50 dose steps (IDegLira) or 50 units (degludec). The primary endpoint was change from baseline in HbA1c with IDegLira vs degludec after 26 weeks of treatment.

Results: In total, 210 Japanese individuals were randomized to IDegLira or degludec and completion rates were 100% and 93%, respectively. IDegLira was superior to degludec with respect to change from baseline in HbA1c: estimated treatment difference (ETD) (95% confidence interval), -13.98 mmol/Mol (-16.41; -11.55); P < 0.0001. The change in mean HbA1c was from 70.6 by -21.3 mmol/Mol with IDegLira and from 70.1 by -7.1 mmol/Mol with degludec. Mean change in body weight was -0.7 kg with IDegLira and 0.7 kg with degludec: ETD (95% CI) -1.41 kg (-2.26; -0.56); P = 0.0012. Mean daily total insulin dose was significantly lower with IDegLira (37.6 U) as compared to that with degludec (41.2 U) at Week 26. Overall rates of severe or blood glucose-confirmed hypoglycaemia and adverse events were comparable between treatment groups.

Conclusions: IDegLira provided superior reductions in HbA1c compared with ≤50 U degludec, with weight loss and similar hypoglycaemia rates and no unexpected safety or tolerability issues. These results suggest that this treatment could be an attractive intensification option for Japanese subjects with T2D that was uncontrolled with basal or pre-mixed insulin.

Keywords: basal insulin; hypoglycaemia; liraglutide; randomized trial; type 2 diabetes.

Figure 1

Trial design. *OAD, one of the following oral anti‐diabetic drugs: sulphonylureas, glinides, α‐glucosidase inhibitors, sodium‐glucose co‐transporter‐2 inhibitors or thiazolidinediones.Maximum doses were 50 dose steps for IDegLira and 50 U for degludec. Metformin was continued at pre‐trial doses. Abbreviations: IDegLira, insulin degludec/liraglutide; OAD, oral anti‐diabetic drug; P, phone contact; V, site visit

Figure 2

Mean change from baseline in HbA1c (A), body weight (B), fasting plasma glucose (C) and total daily insulin dose (D) over time. (A), (B) and (C): Full analysis set. (D): Safety analysis set. Missing values are imputed by last observation carried forward. Error bars are standard error of the mean. Abbreviations: EOT, end of trial; FPG, fasting plasma glucose; IDegLira, insulin degludec/liraglutide

Figure 3

Participants achieving HbA1c outcomes of <53 mmol/Mol (<7.0%) and ≤ 48 mmol/Mol (≤6.5%) (A); participants achieving composite outcomes with HbA1c <53 mmol/Mol (<7.0%) and ≤ 48 mmol/Mol (≤6.5%) without weight gain, without hypoglycaemia and without weight gain or hypoglycaemia (B). Hypoglycaemia was defined as severe according to ADA criteria or blood glucose‐confirmed (<3.1 mmol/L [<56 mg/dL]) episodes. Based on full analysis set. Logistic regression model with treatment and pre‐trial anti‐diabetic treatment as factors and HbA1c baseline value (and weight) as covariate(s). Hypo: Severe or blood glucose‐confirmed symptomatic hypoglycaemia during last 12 weeks of treatment. Missing values were imputed by last observation carried forward. Abbreviations: ADA, American Diabetes Association; CI, confidence interval; hypo, hypoglycaemia; IDegLira, insulin degludec/liraglutide; OR, odds ratio