The Insulin Response to the Gut Hormone GIP After Near-normalisation of Plasma Glucose in Patients With Type 2 Diabetes

NCT04228484 | Completed

• 1 other identifier: H-19069850
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators hypothesise that the insulinotropic effect of endogenous GIP is improvable in patients with type 2 diabetes after three weeks of near-normalisation of plasma glucose. To test this hypothesis, a randomised, placebo-controlled, double-blinded, crossover study employing a GIP receptor antagonist, will be carried out. Fifteen overweight (body mass index (BMI) \> 25 kg/m2) dysregulated (HbA1c \>/= 59 mmol/mol and treatment with metformin or \>53 mmol/mol and treatment with metformin + add/on) patients with type 2 diabetes will attend two experimental days followed by a three-week-four-week period of plasma glucose near-normalisation (achieved by standard treatment of type 2-diabetes), followed by another two experimental days. On experimental days, patients will receive an infusion of GIP receptor antagonist or placebo during a 75 g oral glucose tolerance test. The primary endpoint is changes in levels of C-peptide divided by changes in levels of plasma glucose and secondary endpoints include changes in circulating levels of C-peptide, insulin, glucose, GIP, glucagon-like peptide 1 (GLP-1), glucagon and markers of bone turnover as well as indices of beta cell function. Furthermore, gastric emptying rate will be assessed.

Conditions

Type2 Diabetes

Keywords

Type 2 Diabetes,; Incretin Effect; GIP; Glucose-dependent Insulinotropic Polypeptide

Outcome Measures

Primary Outcomes (1)

• Change in [plasma C-peptide] / [plasma glucose] after near-normalisation of plasma glucose

  The primary endpoint is beta cell sensitivity to glucose as assessed by the C-peptide response to a 75 g-oral glucose tolerance test (OGTT) (as assessed by baseline-subtracted area under the curve (bsAUC)) divided by levels of plasma glucose (as assessed by bsAUC) during GIP(3-30)NH2 infusion compared to placebo before and after near-normalisation of plasma glucose.

  Assessed multiple times on each of the four study days

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo infusion

Other: Placebo

GIP receptor antagonization

ACTIVE COMPARATOR

GIP(3-30)NH2 infusion

Other: GIP receptor antagonization

Interventions

Placebo OTHER

Placebo infusion

Placebo

GIP receptor antagonization OTHER

GIP(3-30)NH2 infusion

GIP receptor antagonization

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 2 diabetes
• Metformin treatment
• Haemoglobin A1c (HbA1c) I. \>/= 59 mmol/mol in case the diabetes treatment is only metformin II. 53-75 mmol/mol in case the diabetes treatment is metformin and add-on therapy
• Body Mass Index (BMI) \> 25 kg/m2
• Age \> 18 years
• Caucasian
• Normal haemoglobin levels

You may not qualify if:

• Treatment with GLP-1-receptor agonist
• Any treatment that cannot be paused for 12 hours
• Diabetes duration more than 20 years
• Weekly alcohol intake of more than 14 units for men or 7 units for women of alcohol (of 12 g) or narcotics abuse
• Liver disease
• Kidney disease (estimated glomerular filtration rate, eGFR \< 60 ml/min/1,73 m2)
• Unusual dietary preferences or planned weight loss within the duration of the study
• Any other condition that in the opinion of the responsible investigators is disqualifying.
• For women I. Current or planned pregnancy for the duration of the study II. Positive pregnancy test at the screening or any of the experimental days III. Women who are currently breastfeeding

Sponsors & Collaborators

• University Hospital, Gentofte, Copenhagen: lead

Study Sites (1)

Center for Clinical Metabolic Research, Gentofte Hospital

Hellerup, Capital Region, 2900, Denmark

Location

Related Publications (1)

• Gasbjerg LS, Helsted MM, Hartmann B, Jensen MH, Gabe MBN, Sparre-Ulrich AH, Veedfald S, Stensen S, Lanng AR, Bergmann NC, Christensen MB, Vilsboll T, Holst JJ, Rosenkilde MM, Knop FK. Separate and Combined Glucometabolic Effects of Endogenous Glucose-Dependent Insulinotropic Polypeptide and Glucagon-like Peptide 1 in Healthy Individuals. Diabetes. 2019 May;68(5):906-917. doi: 10.2337/db18-1123. Epub 2019 Jan 9.

  PMID: 30626611 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Filip K Knop, Professor, MD

  Director of Center for Clinical Metabolic Research, Gentofte Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, MD, PhD

Model Details: Double-blinded randomized placebo-controlled study

Study Record Dates

• First Submitted: January 7, 2020
• First Posted: January 14, 2020
• Study Start: January 7, 2020
• Primary Completion: June 4, 2021
• Study Completion: October 1, 2022
• Last Updated: November 4, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)