Comparison of the Blood Sugar Lowering Effect Between Repaglinide Plus Metformin and Repaglinide Alone in Type 2 Diabetics Not Previously Treated With Oral Sugar-lowering Drugs

Phase 4

Completed

Conditions: Diabetes Mellitus, Type 2
Diabetes

Interventions: Drug: repaglinide
Drug: metformin

Registration Number: NCT00819741

Lead Sponsor: Novo Nordisk A/S

Brief Summary: This trial is conducted in Asia. The aim of this clinical trial is to investigate the blood sugar lowering effect of repaglinide plus metformin as initial treatment compared to repaglinide alone in Chinese subjects with type 2 diabetes having an HbA1c (glycosylated haemoglobin A1c) over 8.5 % and who never have taken oral sugar-lowering drugs before. The associated unfavourable events including low blood sugar episodes between the two treatments are also compared.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 433

Inclusion Criteria

Diagnosed with type 2 diabetes
Never taken oral antidiabetic drugs before
HbA1c greater than 8.5 %
BMI (Body Mass Index) less than or equal to 35 kg/m^2

Exclusion Criteria

Known or suspected allergy to repaglinide, metformin, or any of the excipients in the medications
Taken an investigational drug in another clinical trial within 4 weeks prior to this trial
Impaired liver function, defined as ASAT (aspartate aminotransferase) or ALAT (alanine aminotransferase) equal to or greater than 2 times upper normal limit
Have a clinically significant, active disease of the gastrointestinal, pulmonary, neurological, renal, genitourinary, and haematological systems
Severe uncontrolled or untreated hypertension (sitting diastolic blood pressure (BP) equal to or greater than 100 mmHg or systolic BP equal to or greater than 180 mmHg)
Impaired renal function
Acute or chronic acidosis or if there are plans to have a radiographic material containing iodine
Have a clinically significant, active cardiovascular disease, or decompensated heart failure
Treatment with systemic corticosteroids within the past two months prior to screening

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Repaglinide + metformin	repaglinide	Initial dose of repaglinide 1mg plus metformin 500mg once daily. During the dose titration period of 6 weeks, the dose could be titrated up to repaglinide 4 mg and metformin 500 mg three times daily, according to fasting glucose values. The minimal dose was repaglinide 1 mg plus metformin 500 mg three times daily.
Repaglinide + metformin	metformin	Initial dose of repaglinide 1mg plus metformin 500mg once daily. During the dose titration period of 6 weeks, the dose could be titrated up to repaglinide 4 mg and metformin 500 mg three times daily, according to fasting glucose values. The minimal dose was repaglinide 1 mg plus metformin 500 mg three times daily.
Repaglinide	repaglinide	Initial dose of repaglinide 1 mg three times daily. During the dose titration period of 6 weeks, the dose of repaglinide could be titrated up to 4 mg three times daily, according to fasting glucose values. The minimal dose was repaglinide 1 mg three times daily.

Primary Outcome Measures

Name	Time	Method
Change in Glycosylated Haemoglobin A1c (HbA1c)	week -2 (screening), week 16	Calculated as an estimate of the mean change in HbA1c after 16 weeks of treatment.

Secondary Outcome Measures

Name	Time	Method
Change in 2-hour Postprandial Serum Insulin	Week 0, week 16	Calculated as an estimate of the mean change in 2-hour postprandial serum insulin after 16 weeks of treatment.
Change in Fasting Serum C-peptide	Week 0, week 16	Calculated as an estimate of the mean change in fasting serum C-peptide after 16 weeks of treatment
Change in 2-hour Postprandial Serum C-peptide	Week 0, week 16	Calculated as an estimate of the mean change in 2-hour postprandial serum C-peptide after 16 weeks of treatment
Hypoglycaemic Episodes	Weeks 0-16	Number of hypoglycaemic episodes from Week 0 to Week 16, defined as major, minor or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.
Change in Blood Pressure	Week 0, week 16	Calculated as the mean change in diastolic and systolic blood pressure after 16 weeks of treatment
Change in Fasting Plasma Glucose	week 0, week 16	Calculated as an estimate of the mean change in fasting plasma glucose after 16 weeks of treatment.
Change in 2-hour Postprandial Plasma Glucose	Week 0, week 16	Calculated as an estimate of the mean change in 2-hour postprandial plasma glucose following a standard test meal after 16 weeks of treatment
Change in 7-point Plasma Glucose Profile	Week 0, week 16	Calculated as an estimate of the mean change in 7-point (before breakfast, 2 hours after breakfast, before lunch, 2 hours after lunch, before dinner, 2 hours after dinner, bedtime) plasma glucose profile after 16 weeks of treatment.
Change in Fasting Serum Insulin	Week 0, week 16	Calculated as an estimate of the mean change in fasting serum insulin after 16 weeks of treatment.
Physical Examinations	Week -2, week 16	The number of subjects having a physical examination event that changed from 'Normal' or 'Abnormal, not clinically significant' to 'Abnormal, clinically significant'. Physical examination included cardiovascular system, respiratory system, musculoskeletal system, nervous system and abdomen.
ECG (ElectroCardioGram)	Week -2, week 16	The number of subjects having a electrocardiogram (ECG) that changed from 'Normal' or 'Abnormal, not clinically significant' to 'Abnormal, clinically significant'. 'Abnormal, Clinically significant' is an abnormality that suggests a disease and/or organ toxicity and is of a severity, which requires active management.
Biochemistry: Alanine Aminotransferase (ALAT)	Week -2, week 16	The number of subjects having a change in Alanine Aminotransferase (ALAT) from 'Normal' or 'Abnormal, not clinically significant' to 'Abnormal, clinically significant'. 'Abnormal, Clinically significant' is an abnormality that suggests a disease and/or organ toxicity and is of a severity, which requires active management.
Biochemistry: Alanine Aminotransferase (ASAT)	Week -2, week 16	The number of subjects having a change in Aspartate Aminotransferase (ASAT) from 'Normal' or 'Abnormal, not clinically significant' to 'Abnormal, clinically significant'. 'Abnormal, Clinically significant' is an abnormality that suggests a disease and/or organ toxicity and is of a severity, which requires active management.
Haematology: Haemoglobin	Week -2, week 16	Haemoglobin was measured. The number of subjects having a change in Haemoglobin measurement from 'Normal' or 'Abnormal, not clinically significant' to 'Abnormal, clinically significant' 'Abnormal, Clinically significant' is an abnormality that suggests a disease and/or organ toxicity and is of a severity, which requires active management.