An interventional study of LY2409021 and LY2409021 placebo in Type 2 Diabetes, sponsored by University Hospital, Gentofte, Copenhagen. Completed at 1 site in Denmark. Open to participants aged 35 Years to 80 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2016-10-25.
Sponsored by University Hospital, Gentofte, Copenhagen · Not applicable, Interventional, and Basic science
In patients with type 2 diabetes, the incretin effect is markedly reduced contributing to the relative insulin deficiency that characterizes these patients. This defect is believed to be due to a decreased effect of GLP-1 and an almost ceased effect of GIP. Nevertheless, the impact of the defect on glucose tolerance is not fully understood. The so-called gastrointestinal-mediated glucose disposal (GIGD) is a measure of glucose handling, which includes the incretin effect, but also other factors affecting glucose disposal (e.g. glucagon secretion). Interestingly, patients with type 2 diabetes exhibit elevated plasma glucagon levels in the fasting state, and glucagon concentrations fail to decrease appropriately and may even increase in response to ingestion of glucose and show exaggerated increases after a mixed meal. With the current project the investigators wish to elucidate how this paradoxical glucagon response observed in patients with type 2 diabetes affects the GIGD, the incretin effect and postprandial glucose excursions.
Ten patients with type 2 diabetes and 10 healthy matched control subjects will be enrolled in this randomised, placebo-controlled, double-blinded study. The aim is to examine the effect of a glucagon receptor antagonist (GRA) on gastrointestinal-mediated glucose disposal (GIGD), incretin effect and postprandial glucose excursions in patients with type 2 diabetes and healthy controls. Participants will attend two oral glucose tolerance tests (OGTT), two isoglycaemic iv glucose infusion (IIGI) and two standardised liquid meals.
10,925 studies on the registry are indexed under Diabetes Mellitus; 1,319 are open to participants now.
This study's enrollment of 20 is below the median of 80 across 8,367 interventional studies indexed under Diabetes Mellitus.
Browse Diabetes Mellitus studies →University Hospital, Gentofte, Copenhagen is the lead sponsor of 154 studies on the registry; 9 are open to participants now.
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Patients with type 2 diabetes
Healthy subjects
Exclusion Criteria:
Patients with type 2 diabetes
Healthy subjects
Type 2 diabetes patients + 50 oral glucose tolerance test 4 hours + the human antagonist of the glucagon receptor.
Drug: LY2409021 · Procedure: OGTT
Type 2 diabetes patients + 50 oral glucose tolerance test 4 hours + placebo comparator to the human antagonist of the glucagon receptor.
Drug: LY2409021 placebo · Procedure: OGTT
Type 2 diabetes patients + isoglycaemic iv glucose infusion + the human antagonist of the glucagon receptor.
Drug: LY2409021 · Procedure: IIGI
Type 2 diabetes patients + isoglycaemic iv glucose infusion + placebo comparator to the human antagonist of the glucagon receptor.
Drug: LY2409021 placebo · Procedure: IIGI
Type 2 diabetes patients + Standardised liquid meal + the human antagonist of the glucagon receptor.
Drug: LY2409021 · Procedure: Standardised liquid meal
Type 2 diabetes patients + Standardised liquid meal + placebo comparator to the human antagonist of the glucagon receptor.
Drug: LY2409021 placebo · Procedure: Standardised liquid meal
Healthy controls + 50 oral glucose tolerance test 4 hours + the human antagonist of the glucagon receptor.
Drug: LY2409021 · Procedure: OGTT
Healthy controls + 50 oral glucose tolerance test 4 hours + placebo comparator of the human antagonist of the glucagon receptor.
Drug: LY2409021 placebo · Procedure: OGTT
Healthy controls + isoglycaemic iv glucose infusion + the human antagonist of the glucagon receptor.
Drug: LY2409021 · Procedure: IIGI
Healthy controls + isoglycaemic iv glucose infusion + placebo comparator the human antagonist of the glucagon receptor.
Drug: LY2409021 placebo · Procedure: IIGI
Healthy controls + Standardised liquid meal + the human antagonist of the glucagon receptor.
Drug: LY2409021 · Procedure: Standardised liquid meal
Healthy controls + Standardised liquid meal + placebo comparator of the human antagonist of the glucagon receptor.
Drug: LY2409021 placebo · Procedure: Standardised liquid meal
Differences in GIGD (%)
GIGD = Gastrointestinal glucose disposal. GIGD (%) = 100% × (glucoseOGTT-glucoseIIGI)/glucoseOGTT.
Time frame: Comparison between experimental days with and without the glucagon receptor antagonist . The glucose disposal at time 240 minutes will be used.
Difference in postprandial glucose excursions
Difference in postprandial glucose excursions (measured as incremental (baseline substracted) area under the curve (AUC) values).
Time frame: Area under the curve (AUC) time frame: 0, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 105, 120, 150, 180, 210, 240 minutes. Comparison between experimental days with and without the glucagon receptor antagonist.
Incretin effect
The incretin effect (100% × \[β-cell secretory response to oral glucose tolerance test - intravenous β-cell secretory response\]/β-cell secretory response to oral glucose tolerance test)
Time frame: Insulin AUC time frame: 0,10, 20, 30, 50, 60, 70, 90, 105, 120, 150, 240 minutes. Comparison between experimental days with and without the glucagon receptor antagonist
Endogenous glucose production
Glucose rate of appearance will be calculated by the non-steady state equation using double tracer technique.
Time frame: Plasma concentration of 6,6^2 H2-glucose and U-13C^6-glucose at times: 0,10, 20, 30, 50, 60, 70, 90, 105, 120, 150, 240 minutes.
Lipolysis
Glycerol disappearance will be calculated by the non-steady state equation using double tracer technique.
Time frame: Plasma concentration of 1,1,2,3,3-^2-H5 - glycerol measured at times: 0,10, 20, 30, 50, 60, 70, 90, 105, 120, 150, 240 minutes.
Serum/plasma concentrations of insulin, C-peptide, glucagon, GIP and GLP-1.
Insulin, C-peptide, glucagon, GIP and GLP-1 serum/plasma concentrations will be measured in pM.
Time frame: Time frame: 0,10, 20, 30, 50, 60, 70, 90, 105, 120, 150, 240 minutes.
Appetite
Appetite will be evaluated with a visual analogue scale (VAS).
Time frame: VAS scales will be handed out at time 0, 30, 60, 90, 120, 150, 180 and 240 minutes.
Energy intake (kcal/kJ)
At the end of the clamp experiment food intake will be examined with an ad libitum meal. The weight of the food will be measured i grams and calculated to the energy intake in kcal/kJ.
Time frame: At time 240 to 270, the participants will eat an ad libitum meal. Comparison between experimental days with and without the glucagon receptor antagonist
Changes in blood pressure (mmHg)
Time frame: Measured at time 0 and time 210 minutes. Comparison between experimental days with and without the glucagon receptor antagonist
Changes in pulse rate (beat per minute)
Time frame: Measured at time 0 and at time 210 minutes. Comparison between experimental days with and without the glucagon receptor antagonist
Differences in gastric emptying
Measurement of p-paracetamol. Measurement of time to peak and incremental area under the curve (iAUC)
Time frame: -30,-15, 0, 10, 20, 30, 50, 70, 90, 105, 120, 150, 240 minutes
Free fatty acids
serum values of free fatty acids
Time frame: -30,-15, 0, 10, 20, 30, 50, 70, 90, 105, 120, 150, 240 minutes
Fibroblast growth factor-21
plasma values of FGF-21
Time frame: -30,-15, 0, 10, 20, 30, 50, 70, 90, 105, 120, 150, 240 minutes
Plan to share: Undecided
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University Hospital, Gentofte, Copenhagen