Effects of Rosiglitazone and Metformin on Metabolism in Type 2 Diabetes

Type 2 Diabetes Clinical Trial

— ROSI  

Official title:

Comparison of Effects of Rosiglitazone and Metformin on Myocardial, Skeletal Muscle, Liver and Adipose Tissue Insulin Stimulated Glucose Uptake in Patients With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02526615
• Other study ID #: TurkuUH-ROSI
• Status: Completed
• Phase: Phase 4
• First received: August 11, 2015
• Last updated: August 14, 2015
• Start date: October 2000
• Est. completion date: December 2001

Study information

• Verified date: August 2015
• Source: Turku University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Finland: Finnish Medicines Agency
• Study type: Interventional

Clinical Trial Summary

The objectives of this study are to compare the effects of rosiglitazone and metformin on insulin stimulated glucose uptake in subjects with type 2 diabetes. Whole body, and skeletal muscle, heart and adipose tissue insulin stimulated glucose uptake is measured during euglycemic hyperinsulinemic clamp and positron-emission tomography scanning before and 26 weeks after treatment in 48 newly diagnosed subjects with type 2 diabetes. Subjects will be randomized to receive either rosiglitazone or metformin or placebo, according to a simple randomization procedure with double blinding.

Description:

Insulin resistance is a pivotal underlying metabolic abnormality in most subjects with type 2 diabetes. Clinical experience has proved metformin to be efficacious treatment in patients with type 2 diabetes. Rosiglitazone is a novel antidiabetic agent, which has been shown to decrease fasting plasma glucose concentrations in animal models and in clinical trials. There are no previous studies that compare the effects of rosiglitazone and metformin on insulin stimulated glucose uptake in subjects with type 2 diabetic in different organs.

PET is very sensitive in detecting changes in glucose uptake and blood flow and, is the method of choice to investigate the effects of medical interventions. Due to sensitivity of these functional parameters only moderate or small number of subjects need to be studied. This makes it feasible to perform tightly controlled intervention studies in a very cost-effective way.

The objectives of this study are to compare the effects of rosiglitazone and metformin on insulin stimulated glucose uptake in subjects with type 2 diabetes. PET measurements on myocardium, skeletal muscle and subcutaneous and visceral fat are performed at baseline and at the end of the treatment period. Furthermore, the effect of exercise on skeletal muscle blood flow and glucose uptake is studied.

The study consists of 48 newly diagnosed subjects with type 2 diabetes. Subjects will be randomized to receive either rosiglitazone or metformin or placebo, according to a simple randomization procedure with double blinding. The investigators will also study ten age-matched non-diabetic control subjects, who will undergo the same PET study procedure as subjects with type 2 diabetes.

A study of the effects of antidiabetic oral medication in newly diagnosed subjects with type 2 diabetes is of great importance for the understanding of the differences in mode of action of the different antidiabetic drugs. Such a study would contribute to elucidate advantages and disadvantages with certain drugs and potential additive effects in combination therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: December 2001
• Est. primary completion date: December 2001
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 75 Years

Eligibility

Inclusion Criteria:

• Age 40-75 years,

• BMI 25-35 kg/m2,

• WHO criteria for type 2 diabetes fasting plasma glucose>=7.0 mmol/l on at least 2 separate occasions,

• C-peptide>0.2 nmol/l

Exclusion Criteria:

• plasma glucose < 6.1 or >10 mmol/l after the screening period

• cardiac heart failure

• diagnosed coronary heart disease

• severe aortic, mitral or tricuspidal valve disease

• blood pressure > 160/ 100 mg Hg

• any previous or present hepatic (GT >100, alanine amino transferase >3 x upper limit of the reference range) or renal (S-creatinine > 130) disease

• pregnancy or lactation

• proliferative retinopathy

• microalbuminuria

• subjects with history of lactate acidosis

• symptomatic polyneuropathy

• antidiabetic medication

• changes in antihypertensive medication or beta-blockers in medication

• metal objects in region of imaging

• anemia with Hb < 100 in mean or < 90 in women

• oral corticosteroid treatment

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Insulin Sensitivity
• Type 2 Diabetes

Intervention

Drug:
• Rosiglitazone
Patients received either placebo, metformin or rosiglitazone
• Metformin
Patients received either placebo, metformin or rosiglitazone
• Placebo
Patients received either placebo, metformin or rosiglitazone

Locations

Country	Name	City	State
Finland	Turku PET Centre	Turku
Finland	Turku PET Centre (Turku University Hospital)	Turku
Finland	Turku university hospital, PET center	Turku

Sponsors (2)

Lead Sponsor	Collaborator
Turku University Hospital	SmithKline Beecham

Country where clinical trial is conducted

Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	insulin sensitivity in skeletal muscle	pre and at 26 weeks measured with euglycemic clamp and 18-F-2-fluoro-2-deoxy-D-glucose scanning skeletal muscle	26 weeks	No
Secondary	skeletal muscle blood flow	measured using PET scanning	26 weeks	No
Secondary	insulin signaling pathways in skeletal muscle	measured from muscle biopsies taken before and after intervention	26 weeks	No
Secondary	insulin sensitivity of bone marrow fat	measured using PET images	26 weeks	No
Secondary	insulin stimulated intestinal glucose uptake	measured using PET images	26 weeks	No