Dataset Information

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

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.

SUBMITTER: Holst JJ

PROVIDER: S-EPMC4773967 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Holst Jens J JJ Buse John B JB Rodbard Helena W HW Linjawi Sultan S Woo Vincent C VC Boesgaard Trine Welløv TW Kvist Kajsa K Gough Stephen C SC

Journal of diabetes science and technology 20151006 2

<h4>Objective</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 26443290

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Project description:BackgroundHigh postprandial glucose excursions may increase risk for disease. Individuals have widely varying glucose responses to different meals, and precision nutrition approaches often seek to personalize diets to minimize postprandial glycemic responses as measured by continuous glucose monitors (CGMs). However, it is unknown whether different CGM devices result in concordant meal rankings according to postprandial glycemic excursions.ObjectiveWe explored whether meal rankings according to postprandial glycemic excursions differ between 2 simultaneously worn CGMs.MethodsWe collected 27,489 simultaneous measurements from Dexcom G4 Platinum and Abbott Freestyle Libre Pro CGMs during 28 inpatient days in 16 adults without diabetes. Simultaneous glucose measurements obtained for 2 h following 760 ad libitum meals were used to compare within-subject meal rankings between the CGM devices according to their incremental glucose response.ResultsPostprandial responses to ad libitum meals were highly variable, with the Abbott and Dexcom systems resulting in within-subject incremental mean ± SD glucose CVs of 91.7 ± 1.9% and 94.2 ± 2.7%, respectively. Within-subject meal rankings for incremental glycemic responses were relatively discordant between CGMs, with a mean Kendall rank correlation coefficient of 0.43 ± 0.05. Meals in the bottom compared with those in the top half of incremental glycemic responses ranked by Abbott resulted in 50 ± 10% (P = 0.0002) less glycemic reduction as measured by Dexcom, and vice versa. The missing glycemic reduction by eating meals ranked according to the discordant CGM was inversely correlated with each subject's Kendall rank correlation coefficient (r = -0.95; P < 0.0001).ConclusionsPrecision nutrition approaches that use CGMs to personalize meal recommendations for minimizing glycemic excursions may be premature given the discordance of within-subject meal rankings between simultaneous CGM devices. More research is needed to clarify the source of this imprecision. This trial was registered at clinicaltrials.gov as NCT03407053.

Project description:PurposeSedentary behaviors and muscle inactivity are being growingly recognized as important risk factors for health, adjunctively and independently from a scarce physical activity (PA), although the metabolic mechanism underneath is barely clear. To explore the relation between sedentary behaviors (SBs) and metabolism, we measured the metabolic profile in fasting condition and after oral glucose overload in a group of women, along with objective monitoring of their PA/sedentary lifestyle habits.Subjects and methodsThirteen women (age: 32.5 ± 16.1 years; BMI: 24.0 ± 3.3 kg/m2), recruited among university students and research staff, underwent indirect calorimetry to assess fat and carbohydrate contribution to energy metabolism, in fasting conditions and after a glucose-rich standard meal (about 45 g of glucose). Glucose concentration in capillary blood was determined in fasting state and 15 and 30 min after meal. Habitual PA and SBs in the previous week were continuously monitored with Actigraph accelerometers.ResultsAfter adjustment for age, the contribution of fat oxidation to metabolic energy sources, normalized for fat-free mass, in fasting conditions was significantly correlated with time spent in sitting/lying position during wake hours (p < 0.001), independent from PA habits, whereas capillary blood peak and change of glucose concentration after the meal were significantly and inversely correlated with average daily moderate to vigorous PA (p = 0.025 and p = 0.019, respectively), independent from average daily sitting/lying time.ConclusionsHere, we report for the first time a direct effect of muscle inactivity on increased fat oxidation in fasting conditions, which can be hypothesized as a preliminary condition for the development of insulin resistance. We also report the direct independent effect of PA on the capacity to respond to a glycemic load, so that SBs and reduced PA appear to concur, although independently, to the increased health risk, as elsewhere observed on an epidemiological ground.

Dataset Information

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

Objective

Methods

Results

Conclusions

Publications

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

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