The Effect of GIP and GLP-1 on Insulin and Glucagon Secretion in Patients With HNF1A-diabetes Treated With or Without Sulphonylurea

NCT03081676 | Completed DMC

• 1 other identifier: H-16038140
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The most prevalent monogenetic diabetic subtype is named maturity onset diabetes of the young type (MODY3) or hepatocyte nuclear factor 1α (HNF1A)-diabetes. The aim of this study is to evaluate the effects of supra-physiological levels of GIP and GLP-1, respectively, on insulin and glucagon secretion at fasting plasma glucose (FPG) and "post-prandial" PG levels (1.5 × FPG) in patients with HNF1A-diabetes and matched healthy controls treated with or without a low dose of glimepiride (sulphonylurea). In addition, we will evaluate the maximal insulin and glucagon secretory capacity in both groups.

Conditions

Maturity-Onset Diabetes of the Young, Type 3

Keywords

Maturity-Onset Diabetes of the Young, Type 3; Glucose-dependent insulinotropic peptide; Glucagon-like-peptide 1; Dipeptidyl peptidase 4; Glimepiride; Sulphonylurea; Glucose clamp; Hepatocyte nuclear factor 1 alpha

Outcome Measures

Primary Outcomes (1)

• Insulin secretion

  Incremental area under the curve (iAUC) for insulin (measured as C-peptide) at time 0-60 minutes, time 60-120 minutes and time 0-120 minutes

  0-120 minutes

Secondary Outcomes (4)

• Glucagon secretion

  0-120 minutes

• Maximal insulin secretion

  120-125 minutes

• Maximal glucagon secretion

  120-125 minutes

• Amount glucose used to maintain the glucose clamp

  0-120 minutes

Study Arms (6)

Glimepiride + GIP

ACTIVE COMPARATOR

Tablet Glimepiride + infusion of GIP

Drug: Glimepiride 1Mg Tablet; Drug: Glucose-Dependent Insulinotropic Polypeptide

Placebo + GIP

ACTIVE COMPARATOR

Placebo tablet + infusion of GIP

Drug: Glucose-Dependent Insulinotropic Polypeptide; Drug: Placebo Oral Tablet

Glimepiride + GLP-1

ACTIVE COMPARATOR

Glimepiride + infusion of GLP-1

Drug: Glimepiride 1Mg Tablet; Drug: Glucagon-like Peptide-1

Placebo + GLP-1

ACTIVE COMPARATOR

Placebo tablet + infusion of GLP-1

Drug: Glucagon-like Peptide-1; Drug: Placebo Oral Tablet

Glimepiride + Placebo

ACTIVE COMPARATOR

Glimepiride + infusion of placebo (saline)

Drug: Glimepiride 1Mg Tablet; Drug: Placebo infusion

Placebo + Placebo

PLACEBO COMPARATOR

Placebo tablet + infusion of placebo (saline)

Drug: Placebo Oral Tablet; Drug: Placebo infusion

Interventions

Glimepiride 1Mg Tablet DRUG

Glimepiride

Glimepiride + GIP; Glimepiride + GLP-1; Glimepiride + Placebo

Glucagon-like Peptide-1 DRUG

GLP-1 infusion

Glimepiride + GLP-1; Placebo + GLP-1

Glucose-Dependent Insulinotropic Polypeptide DRUG

GIP-infusion

Glimepiride + GIP; Placebo + GIP

Placebo Oral Tablet DRUG

Placebo

Placebo + GIP; Placebo + GLP-1; Placebo + Placebo

Placebo infusion DRUG

Placebo (saline)

Glimepiride + Placebo; Placebo + Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Patients with HNF1A-diabetes verified by genetic testing
• Patients treated with diet or sulphonylurea monotherapy
• Normal haemoglobin (males 8.3-10.5 mmol/l, females 7.3-9.5 mmol/l)
• Informed consent
• Nephropathy (estimated glomerular filtration rate (eGFR) \<60 ml/min/1.73m2 and/or albuminuria)
• Liver disease (serum alanine aminotransferase (ALT) and/or serum aspartate aminotransferase (AST) above 2 × normal values)
• Pregnancy or breastfeeding
• FPG ≤6 mmol/l and glycated haemoglobin (HbA1c) ≤43 mmol/mol
• Normal haemoglobin as defined above
• Age ≥18 years
• Informed consent
• No family history of type 1 or type 2 diabetes
• Nephropathy (defined above)
• Liver disease (defined above)
• Pregnancy or breastfeeding

Sponsors & Collaborators

• University Hospital, Gentofte, Copenhagen: lead

Study Sites (1)

Center for Diabetes Research, Gentofte Hospital

Hellerup, 2900, Denmark

Location

Related Publications (1)

• Christensen AS, Haedersdal S, Storgaard H, Rose K, Hansen NL, Holst JJ, Hansen T, Knop FK, Vilsboll T. GIP and GLP-1 Potentiate Sulfonylurea-Induced Insulin Secretion in Hepatocyte Nuclear Factor 1alpha Mutation Carriers. Diabetes. 2020 Sep;69(9):1989-2002. doi: 10.2337/db20-0074. Epub 2020 Jun 9.

  PMID: 32518064 DERIVED

MeSH Terms

Conditions

Maturity-Onset Diabetes of the Young, Type 3

Interventions

glimepiride; Tablets; Glucagon-Like Peptide 1; Incretins

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Design

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

Study Record Dates

• First Submitted: March 10, 2017
• First Posted: March 16, 2017
• Study Start: March 8, 2017
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: June 27, 2019

Record last verified: 2019-06

Locations

DK (1)