NCT02669524

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at below P25 for not_applicable type-2-diabetes

Timeline
Completed

Started Oct 2015

Shorter than P25 for not_applicable type-2-diabetes

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2015

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

December 14, 2015

Completed
2 months until next milestone

First Posted

Study publicly available on registry

February 1, 2016

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2016

Completed
Last Updated

October 25, 2016

Status Verified

October 1, 2016

Enrollment Period

10 months

First QC Date

December 14, 2015

Last Update Submit

October 24, 2016

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (2)

  • Differences in GIGD (%)

    GIGD = Gastrointestinal glucose disposal. GIGD (%) = 100% × (glucoseOGTT-glucoseIIGI)/glucoseOGTT.

    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).

    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.

Secondary Outcomes (11)

  • Incretin effect

    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

    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

    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.

    Time frame: 0,10, 20, 30, 50, 60, 70, 90, 105, 120, 150, 240 minutes.

  • Appetite

    VAS scales will be handed out at time 0, 30, 60, 90, 120, 150, 180 and 240 minutes.

  • +6 more secondary outcomes

Study Arms (12)

T2D + OGTT + LY2409021

ACTIVE COMPARATOR

Type 2 diabetes patients + 50 oral glucose tolerance test 4 hours + the human antagonist of the glucagon receptor.

Drug: LY2409021Procedure: OGTT

T2D + OGTT + placebo

PLACEBO COMPARATOR

Type 2 diabetes patients + 50 oral glucose tolerance test 4 hours + placebo comparator to the human antagonist of the glucagon receptor.

Drug: LY2409021 placeboProcedure: OGTT

T2D + IIGI + LY2409021

ACTIVE COMPARATOR

Type 2 diabetes patients + isoglycaemic iv glucose infusion + the human antagonist of the glucagon receptor.

Drug: LY2409021Procedure: IIGI

T2D + IIGI + placebo

PLACEBO COMPARATOR

Type 2 diabetes patients + isoglycaemic iv glucose infusion + placebo comparator to the human antagonist of the glucagon receptor.

Drug: LY2409021 placeboProcedure: IIGI

T2D + MEAL + LY2409021

ACTIVE COMPARATOR

Type 2 diabetes patients + Standardised liquid meal + the human antagonist of the glucagon receptor.

Drug: LY2409021Procedure: Standardised liquid meal

T2D + MEAL + placebo

PLACEBO COMPARATOR

Type 2 diabetes patients + Standardised liquid meal + placebo comparator to the human antagonist of the glucagon receptor.

Drug: LY2409021 placeboProcedure: Standardised liquid meal

CTRL + OGTT + LY2409021

ACTIVE COMPARATOR

Healthy controls + 50 oral glucose tolerance test 4 hours + the human antagonist of the glucagon receptor.

Drug: LY2409021Procedure: OGTT

CTRL + OGTT + placebo

PLACEBO COMPARATOR

Healthy controls + 50 oral glucose tolerance test 4 hours + placebo comparator of the human antagonist of the glucagon receptor.

Drug: LY2409021 placeboProcedure: OGTT

CTRL + IIGI + LY2409021

ACTIVE COMPARATOR

Healthy controls + isoglycaemic iv glucose infusion + the human antagonist of the glucagon receptor.

Drug: LY2409021Procedure: IIGI

CTRL + IIGI + placebo

PLACEBO COMPARATOR

Healthy controls + isoglycaemic iv glucose infusion + placebo comparator the human antagonist of the glucagon receptor.

Drug: LY2409021 placeboProcedure: IIGI

CTRL + MEAL + LY2409021

ACTIVE COMPARATOR

Healthy controls + Standardised liquid meal + the human antagonist of the glucagon receptor.

Drug: LY2409021Procedure: Standardised liquid meal

CTRL + MEAL + placebo

PLACEBO COMPARATOR

Healthy controls + Standardised liquid meal + placebo comparator of the human antagonist of the glucagon receptor.

Drug: LY2409021 placeboProcedure: Standardised liquid meal

Interventions

LY2409021DRUG
CTRL + IIGI + LY2409021CTRL + MEAL + LY2409021CTRL + OGTT + LY2409021T2D + IIGI + LY2409021T2D + MEAL + LY2409021T2D + OGTT + LY2409021
LY2409021 placeboDRUG
CTRL + IIGI + placeboCTRL + MEAL + placeboCTRL + OGTT + placeboT2D + IIGI + placeboT2D + MEAL + placeboT2D + OGTT + placebo
OGTTPROCEDURE
CTRL + OGTT + LY2409021CTRL + OGTT + placeboT2D + OGTT + LY2409021T2D + OGTT + placebo
IIGIPROCEDURE
CTRL + IIGI + LY2409021CTRL + IIGI + placeboT2D + IIGI + LY2409021T2D + IIGI + placebo
Standardised liquid mealPROCEDURE
CTRL + MEAL + LY2409021CTRL + MEAL + placeboT2D + MEAL + LY2409021T2D + MEAL + placebo

Eligibility Criteria

Age35 Years - 80 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with type 2 diabetes
  • Caucasians above 35 years of age with diet or metformin treated type 2 diabetes for at least 3 month (diagnosed according to the criteria of the World Health Organization (WHO)
  • Normal haemoglobin
  • Informed consent
  • Healthy subjects
  • Normal fasting plasma glucose (FPG) \<6.1 mmol/l and HbA1c \<42 mmol/mol (6.0%)
  • Normal haemoglobin
  • Age above 35 years
  • Informed consent

You may not qualify if:

  • Patients with type 2 diabetes
  • Inflammatory bowel disease
  • Intestinal resections
  • Nephropathy (serum creatinine above normal range and/or albuminuria)
  • Liver disease (serum alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) \>2×normal values)
  • Treatment with medicine that cannot be paused for 12 hours
  • Pregnancy and/or breastfeeding
  • Family history of pancreatic islet tumours
  • Age above 80 years
  • Healthy subjects
  • Diabetes or prediabetes with reduced glucose tolerance: FPG \>6.0 mmol/l and/or HbA1c \>42 mmol/mol
  • First degree relatives with type 2 diabetes
  • Inflammatory bowel disease
  • Intestinal resections
  • Treatment with medicine that cannot be paused for 12 hours
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Center for Diabetes Research, Gentofte Hospital, Copenhagen University

Hellerup, DK-2900, Denmark

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

adomeglivantGlucose Tolerance Test

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

Blood Chemical AnalysisClinical Chemistry TestsClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisDiagnostic Techniques, EndocrineInvestigative Techniques

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, PhD student

Study Record Dates

First Submitted

December 14, 2015

First Posted

February 1, 2016

Study Start

October 1, 2015

Primary Completion

August 1, 2016

Study Completion

August 1, 2016

Last Updated

October 25, 2016

Record last verified: 2016-10

Locations

DK(1)