A Fixed Ratio Combination of Insulin Degludec and Liraglutide (IDegLira) Reduces Glycemic Fluctuation and Brings More Patients with Type 2 Diabetes Within Blood Glucose Target Ranges

Abstract

Background: Reducing glycemic fluctuation is important for optimal diabetes management. This post hoc analysis examined glycemic fluctuations and the proportion of subjects achieving recommended blood glucose targets with the fixed ratio combination of insulin degludec and liraglutide (IDegLira) compared to insulin degludec (IDeg) and liraglutide alone.

Methods: We analyzed nine-point self-monitored blood glucose (SMBG) profiles from two randomized trials involving IDegLira in patients with type 2 diabetes (T2D), and continuous glucose monitoring (CGM) data from a subset of patients in one of these trials to assess glycemic fluctuation and day-to-day variability.

Results: Compared with IDeg, IDegLira resulted in a greater proportion of subjects with SMBG values within target ranges (3.9-9.0 mmol/L) than IDeg for all pre- and postprandial values, and for the full nine-point profile (P < 0.05 for all). IDegLira also resulted in a greater reduction in the range of SMBG values over 24 h than IDeg (P ≤ 0.0001). CGM data showed that IDegLira provided greater reductions in interstitial glucose (IG) fluctuation (P = 0.0018) and postprandial IG increment (P = 0.0288) compared with IDeg. Compared with liraglutide, IDegLira brought a higher proportion of subjects within SMBG target ranges (all pre- and all postprandial values, and the full nine-point profile, P < 0.01 for all) and resulted in a greater reduction of time outside the IG target range (P = 0.0072). IDegLira also reduced mean IG more than liraglutide (P < 0.0001).

Conclusions: Treatment with IDegLira allows more patients with T2D to maintain blood glucose within target ranges throughout the day than either IDeg or liraglutide alone.

Trial registration: ClinicalTrials.gov NCT01336023 NCT01392573.

Keywords: Continuous glucose monitoring; GLP-1 analog; Insulin degludec; Liraglutide; Type 2 diabetes.

Conflict of interest statement

A.B.K. has received research support from Sanofi, Lilly, Novo Nordisk, Medtronic, Animas, Takeda, and Amylin, speaker fees from Sanofi, Lilly, Novo Nordisk, Medtronic, Animas, Takeda, Janssen, Lifescan, Pfizer, GlaxoSmithKline, and Amylin, and he has acted as a consultant to Sanofi, Lilly, Novo Nordisk, Medtronic, Animas, Takeda, Janssen, and Lifescan. A.P.-T. has served on behalf of her organization on advisory panels for Eli Lilly, Novo Nordisk, Merck and Co., and Sanofi-Aventis, and she has received research support from Mylan, Lexicon, DexCom, Novo Nordisk, Sanofi-Aventis, Eli Lilly and Company, and AstraZeneca LP. AP-T does not receive any personal reimbursement for these functions. E.S.K. has served on advisory panels for Novo Nordisk and Pfizer. K.B. and I.H.L. are full-time employees of, and own stock at, Novo Nordisk A/S. T.V. has received lecture fees from Amgen, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly and Company, Merck Sharp & Dohme, Novo Nordisk, Novartis, Sanofi, and Zealand Pharma, and has been an advisory-board member for Amgen, Janssen, Novo Nordisk, Merck Sharp & Dohme, Takeda, and Bristol-Myers Squibb/AstraZeneca.

Figures

FIG. 1.

Nine-point SMBG† profile‡ showing calculation of range (a) and change from baseline to EOT in DUAL I and DUAL II (b). †SMBG assessed with glucose meter as plasma equivalent values of capillary whole blood glucose. ‡Illustrative example not intended to represent actual patients or treatment effects. Data are based on FAS, with LOCF for all subjects with a full nine-point profile at baseline; P-values are from ANCOVA with treatment, region, baseline HbA1c stratum (≤8.3% [≤67 mmol/mol], >8.3% [>67 mmol/mol]), and previous OAD treatment as fixed effects, and baseline value of the parameter included as covariate. ANCOVA, analysis of covariance; EOT, end-of-trial; ETD, estimated treatment difference; FAS, full analysis set; HbA1c, glycosylated hemoglobin; IDeg, insulin degludec; IDegLira, fixed ratio combination of insulin degludec and liraglutide; Lira, liraglutide; LOCF, last observation carried forward; OAD, oral antidiabetic drug; NS, not significant; SMBG, self-monitored blood glucose.

FIG. 2.

Time (%) above (IG ≥9.0 mmol/L), within (3.9≤ IG 1c stratum (≤8.3% [≤67 mmol/mol], >8.3% [>67 mmol/mol]) and previous OAD treatment as fixed effects for both methods. CGM, continuous glucose monitoring; CI, confidence interval; IG, interstitial glucose; Lira, liraglutide; SD, standard deviation.