Glimepiride monotherapy vs. combination of glimepiride and linagliptin therapy in patients with maturity onset diabetes of the young type 3 (MODY3)

Glimepiride monotherapy vs. combination of glimepiride and linagliptin therapy in patients with HNF1A-diabetes - GLIMLINA-trial

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2017-000204-15-DK

Enrollment

Registered

2017-05-22

Start date

2017-08-08

Completion date

Unknown

Last updated

2019-11-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

"Hepatocyte nuclear factor 1-alfa diabetes", also called "Maturity onset diabetes of the young type 3"'. It is a monogenic form of inherited diabetes. MedDRA version: 20.0 Level: LLT Classification code 10026948 Term: Maturity-onset diabetes of the young System Organ Class: 100000004861

Interventions

Trade Name: Glimepiride STADA Pharmaceutical Form: Tablet INN or Proposed INN: GLIMEPIRIDE CAS Number: 93479-97-1 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 1

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: • Patients with hepatocyte nuclear factor 1-alpha (HNF1A) diabetes caused by heterozygous mutation in HNF1A confirmed by Sanger sequencing of the gene • Monotherapy with diet or a stable dose of glimepiride of (=0.5 mg per day) during four weeks • Patients on glimepiride HbA1c =6.5% (HbA1c =47 mmol/mol); treatment naïve patients HbA1c =7.0% (HbA1c =53 mmol/mol) • Age =18 years of age • Capability to perform a 30 minute light bicycle test at a heart rate of 100-120 beats per min • Fertile females: use of anticonception (intrauterine contraceptive devices or hormonal contraception) • Informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 18 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2

Exclusion criteria

Exclusion criteria: • Glucose-lowering drugs other than glimepiride • Uraemia, end-stage renal disease or estimated glomerular filtration rate 2 × upper normal serum levels • Anaemia (males blood haemoglobin <8.0 mmol/l and females <7.0 mmol/l) • History of acute and/or chronic pancreatitis • Pregnancy or breast feeding • Inability to complete the study • Known allergic reaction to study medication • Intention to become pregnant

Design outcomes

Primary

Measure	Time frame
Main Objective: The objective of this trial is to investigate the effect of glimepiride + linagliptin vs. glimepiride + placebo on glycaemic variability in patients with hepatocyte nuclear factor 1-alpha (HNF1A) diabetes in a double-blind, randomised, cross-over trial. HNF1A-diabetes is also known as maturity onset diabetes of the young type 3 (MODY3).;Secondary Objective: Among other to investigate longterm glycaemic control (HbA1c) and risk of hypoglycaemia during treatment. ;Primary end point(s): Mean amplitude of glycaemic excursions (MAGE) The primary endpoint is the absolute difference in MAGE between the two treatments (glimepiride + linagliptin vs. glimepiride + placebo) at the end of each treatment period calculated from six days (144 hours) of continuous glucose monitoring (CGM). ;Timepoint(s) of evaluation of this end point: At baseline and end of both treatment periods.	—

Measure

Time frame

Main Objective: The objective of this trial is to investigate the effect of glimepiride + linagliptin vs. glimepiride + placebo on glycaemic variability in patients with hepatocyte nuclear factor 1-alpha (HNF1A) diabetes in a double-blind, randomised, cross-over trial. HNF1A-diabetes is also known as maturity onset diabetes of the young type 3 (MODY3).;Secondary Objective: Among other to investigate longterm glycaemic control (HbA1c) and risk of hypoglycaemia during treatment. ;Primary end point(s): Mean amplitude of glycaemic excursions (MAGE) The primary endpoint is the absolute difference in MAGE between the two treatments (glimepiride + linagliptin vs. glimepiride + placebo) at the end of each treatment period calculated from six days (144 hours) of continuous glucose monitoring (CGM). ;Timepoint(s) of evaluation of this end point: At baseline and end of both treatment periods.

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Secondary

Measure	Time frame
Secondary end point(s): Secondary endpoints include differences between the two treatments (glimepiride + linagliptin vs. glimepiride + placebo) in: • Other parameters of glycaemic variability including low blood glucose index (LBGI), standard deviation of mean glucose, time spent in hypoglycaemia and time spent in hyperglycaemia calculated from six days of CGM at the end of each treatment period . • Difference between baseline and end of treatment in parameters of glycaemic variability including MAGE, LBGI, standard deviation of mean glucose, time spent in hypoglycaemia, time spent in hyperglycaemia from six days of CGM monitoring. • Glycaemic excursion and endocrine function during a 4-hour meal and bicycle test • Plasma/serum concentrations of insulin, C-peptide, glucagon, GIP, GLP-1, growth hormone (GH), cortisol, epinephrine and norepinephrine during a 4-hour meal and bicycle test • Number and severity of hypoglycaemic events during meal and bicycle tests • Number and severity of hypoglycaemic events during treatment periods • Fasting plasma glucose (FPG) at the end of each treatment period • Glycated haemoglobin (HbA1c) at end of trial • Change in bodyweight from baseline • Change in fructosamine at end of treatment • Changes in cardiovascular biomarkers in urine • Changes in quality of life from baseline evaluated with Short Form 36 (SF-36);Timepoint(s) of evaluation of this end point: At baseline and in the end of each treatment period.	—

Measure

Time frame

Secondary end point(s): Secondary endpoints include differences between the two treatments (glimepiride + linagliptin vs. glimepiride + placebo) in: • Other parameters of glycaemic variability including low blood glucose index (LBGI), standard deviation of mean glucose, time spent in hypoglycaemia and time spent in hyperglycaemia calculated from six days of CGM at the end of each treatment period . • Difference between baseline and end of treatment in parameters of glycaemic variability including MAGE, LBGI, standard deviation of mean glucose, time spent in hypoglycaemia, time spent in hyperglycaemia from six days of CGM monitoring. • Glycaemic excursion and endocrine function during a 4-hour meal and bicycle test • Plasma/serum concentrations of insulin, C-peptide, glucagon, GIP, GLP-1, growth hormone (GH), cortisol, epinephrine and norepinephrine during a 4-hour meal and bicycle test • Number and severity of hypoglycaemic events during meal and bicycle tests • Number and severity of hypoglycaemic events during treatment periods • Fasting plasma glucose (FPG) at the end of each treatment period • Glycated haemoglobin (HbA1c) at end of trial • Change in bodyweight from baseline • Change in fructosamine at end of treatment • Changes in cardiovascular biomarkers in urine • Changes in quality of life from baseline evaluated with Short Form 36 (SF-36);Timepoint(s) of evaluation of this end point: At baseline and in the end of each treatment period.

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Countries

Denmark

Contacts

Public ContactClinical Metabolic Physiology

Steno Diabetes Center Copenhagen, Gentofte Hospital

tina.vilsboell.lauritsen.01@regionh.dk

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026