Effects of Rosiglitazone and Metformin on Metabolism in Type 2 Diabetes

Phase 4

Completed

• Conditions: Type 2 Diabetes; Insulin Sensitivity
• Interventions: Drug: Placebo; Drug: Metformin; Drug: Rosiglitazone

• Registration Number: NCT02526615
• Lead Sponsor: Turku University Hospital

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2000-10
• Primary Completion: 2001-12
• Study Completion: 2001-12
• Status Verified: 2015-08
• Study First Submitted: 2015-08-11
• Study First Submitted QC: 2015-08-14
• Last Update Submitted: 2015-08-14
• Study First Posted: 2015-08-18
• Last Update Posted: 2015-08-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 48

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	placebo, 2 tablets per day
Metformin	Metformin	500mg 1 tablet 2 times per day for the first 2 weeks, then after that 2 tables 2 times per day
Rosiglitazone	Rosiglitazone	2 mg 1 tablets 2 times per day for the first 2 weeks, then after that 2 tablets 2 times per day

Primary Outcome Measures

Name	Time	Method
insulin sensitivity in skeletal muscle	26 weeks	pre and at 26 weeks measured with euglycemic clamp and 18-F-2-fluoro-2-deoxy-D-glucose scanning skeletal muscle

Secondary Outcome Measures

Name	Time	Method
skeletal muscle blood flow	26 weeks	measured using PET scanning
insulin signaling pathways in skeletal muscle	26 weeks	measured from muscle biopsies taken before and after intervention
insulin sensitivity of bone marrow fat	26 weeks	measured using PET images
insulin stimulated intestinal glucose uptake	26 weeks	measured using PET images

Trial Locations

Locations (3)

Turku PET Centre; 🇫🇮 Turku, Finland

Turku university hospital, PET center; 🇫🇮 Turku, Finland

Turku PET Centre (Turku University Hospital); 🇫🇮 Turku, Finland