Dissection of the Gastrointestinal-mediated Glucose Disposal and Incretin Defect in Patients With Type 2 Diabetes

U

University Hospital, Gentofte, Copenhagen

Status

Completed

Conditions

Type 2 Diabetes

Treatments

Drug: LY2409021 placebo
Procedure: Standardised liquid meal
Drug: LY2409021
Procedure: OGTT
Procedure: IIGI

Study type

Interventional

Funder types

Other
Industry

Identifiers

NCT02669524
H-15007312

Details and patient eligibility

About

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.

Enrollment

20 patients

Sex

All

Ages

35 to 80 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

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√ónormal 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
  • Pregnancy and/or breastfeeding
  • Age above 80 years

Trial design

Primary purpose

Basic Science

Allocation

Randomized

Interventional model

Crossover Assignment

Masking

Double Blind

20 participants in 12 patient groups, including a placebo group

T2D + OGTT + LY2409021
Active Comparator group
Description:
Type 2 diabetes patients + 50 oral glucose tolerance test 4 hours + the human antagonist of the glucagon receptor.
Treatment:
Procedure: OGTT
Drug: LY2409021
T2D + OGTT + placebo
Placebo Comparator group
Description:
Type 2 diabetes patients + 50 oral glucose tolerance test 4 hours + placebo comparator to the human antagonist of the glucagon receptor.
Treatment:
Procedure: OGTT
Drug: LY2409021 placebo
T2D + IIGI + LY2409021
Active Comparator group
Description:
Type 2 diabetes patients + isoglycaemic iv glucose infusion + the human antagonist of the glucagon receptor.
Treatment:
Procedure: IIGI
Drug: LY2409021
T2D + IIGI + placebo
Placebo Comparator group
Description:
Type 2 diabetes patients + isoglycaemic iv glucose infusion + placebo comparator to the human antagonist of the glucagon receptor.
Treatment:
Procedure: IIGI
Drug: LY2409021 placebo
T2D + MEAL + LY2409021
Active Comparator group
Description:
Type 2 diabetes patients + Standardised liquid meal + the human antagonist of the glucagon receptor.
Treatment:
Drug: LY2409021
Procedure: Standardised liquid meal
T2D + MEAL + placebo
Placebo Comparator group
Description:
Type 2 diabetes patients + Standardised liquid meal + placebo comparator to the human antagonist of the glucagon receptor.
Treatment:
Procedure: Standardised liquid meal
Drug: LY2409021 placebo
CTRL + OGTT + LY2409021
Active Comparator group
Description:
Healthy controls + 50 oral glucose tolerance test 4 hours + the human antagonist of the glucagon receptor.
Treatment:
Procedure: OGTT
Drug: LY2409021
CTRL + OGTT + placebo
Placebo Comparator group
Description:
Healthy controls + 50 oral glucose tolerance test 4 hours + placebo comparator of the human antagonist of the glucagon receptor.
Treatment:
Procedure: OGTT
Drug: LY2409021 placebo
CTRL + IIGI + LY2409021
Active Comparator group
Description:
Healthy controls + isoglycaemic iv glucose infusion + the human antagonist of the glucagon receptor.
Treatment:
Procedure: IIGI
Drug: LY2409021
CTRL + IIGI + placebo
Placebo Comparator group
Description:
Healthy controls + isoglycaemic iv glucose infusion + placebo comparator the human antagonist of the glucagon receptor.
Treatment:
Procedure: IIGI
Drug: LY2409021 placebo
CTRL + MEAL + LY2409021
Active Comparator group
Description:
Healthy controls + Standardised liquid meal + the human antagonist of the glucagon receptor.
Treatment:
Drug: LY2409021
Procedure: Standardised liquid meal
CTRL + MEAL + placebo
Placebo Comparator group
Description:
Healthy controls + Standardised liquid meal + placebo comparator of the human antagonist of the glucagon receptor.
Treatment:
Procedure: Standardised liquid meal
Drug: LY2409021 placebo

Trial contacts and locations

1

Loading...

Data sourced from clinicaltrials.gov

Clinical trials

Find clinical trialsTrials by location
© Copyright 2024 Veeva Systems