IDegLira Improves Both Fasting and Postprandial Glucose Control as Demonstrated Using Continuous Glucose Monitoring and a Standardized Meal Test

Jens J Holst; John B Buse; Helena W Rodbard; Sultan Linjawi; Vincent C Woo; Trine Welløv Boesgaard; Kajsa Kvist; Stephen C Gough

doi:10.1177/1932296815610124

IDegLira Improves Both Fasting and Postprandial Glucose Control as Demonstrated Using Continuous Glucose Monitoring and a Standardized Meal Test

J Diabetes Sci Technol. 2015 Oct 6;10(2):389-97. doi: 10.1177/1932296815610124.

Authors

Jens J Holst¹, John B Buse², Helena W Rodbard³, Sultan Linjawi⁴, Vincent C Woo⁵, Trine Welløv Boesgaard⁶, Kajsa Kvist⁶, Stephen C Gough⁷

Affiliations

¹ NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Copenhagen, Denmark jjholst@sund.ku.dk holst@mfi.ku.dk.
² University of North Carolina, Chapel Hill, NC, USA.
³ Endocrine and Metabolic Consultants, Rockville, MD, USA.
⁴ Coffs Harbour Diabetes Clinic, Coffs Harbour, Australia.
⁵ University of Manitoba, Winnipeg, MB, Canada.
⁶ Novo Nordisk A/S, Søborg, Denmark.
⁷ Oxford Centre for Diabetes, Endocrinology and Metabolism, and NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, UK.

Abstract

Objective: IDegLira is a novel, fixed-ratio combination of the long-acting basal insulin, insulin degludec, and the long-acting glucagon-like peptide-1 analog liraglutide. We studied the effect of IDegLira versus its components on postprandial glucose (PPG) in type 2 diabetes.

Methods: In this substudy, 260 (15.6%) of the original 1663 patients with inadequate glycemic control participating in a 26-week, open-label trial (DUAL I) were randomized 2:1:1 to once-daily IDegLira, insulin degludec or liraglutide. Continuous glucose monitoring (CGM) for 72 hours and a meal test were performed.

Results: At week 26, IDegLira produced a significantly greater decrease from baseline in mean PPG increment (normalized iAUC0-4h) than insulin degludec (estimated treatment difference [ETD] -12.79 mg/dl [95% CI: -21.08; -4.68], P = .0023) and a similar magnitude of decrease as liraglutide (ETD -1.62 mg/dl [95% CI: -10.09; 6.67], P = .70). CGM indicated a greater reduction in change from baseline in PPG increment (iAUC0-4h) for IDegLira versus insulin degludec over all 3 main meals (ETD -6.13 mg/dl [95% CI: -10.27, -1.98], P = .0047) and similar reductions versus liraglutide (ETD -1.80 mg/dl [95% CI: -2.52, 5.95], P = .4122). Insulin secretion ratio and static index were greater for IDegLira versus insulin degludec (P = .048 and P = .006, respectively) and similar to liraglutide (P = .45 and P = .895, respectively).

Conclusions: Once-daily IDegLira provides significantly better PPG control following a mixed meal test than insulin degludec. The improvement is at least partially explained by higher endogenous insulin secretion and improved beta cell function with IDegLira. The benefits of liraglutide on PPG control are maintained across all main meals in the combination.

Trial registration: ClinicalTrials.gov NCT01336023.

Keywords: combination therapy; diabetes therapy; incretins; insulin degludec; liraglutide; postprandial glucose; quality of glycemic control.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Blood Glucose / drug effects*
Diabetes Mellitus, Type 2 / blood
Diabetes Mellitus, Type 2 / drug therapy*
Drug Combinations
Fasting
Female
Humans
Hypoglycemic Agents / therapeutic use*
Insulin, Long-Acting / administration & dosage*
Liraglutide / administration & dosage*
Male
Middle Aged
Monitoring, Physiologic
Postprandial Period

Substances

Blood Glucose
Drug Combinations
Hypoglycemic Agents
Insulin, Long-Acting
insulin degludec
Liraglutide

Associated data

ClinicalTrials.gov/NCT01336023