Effects of Rosiglitazone and Metformin on Metabolism in Type 2 Diabetes

NCT ID: NCT02526615

Last Updated: 2015-08-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-10-31
• Study Completion Date: 2001-12-31

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.

Conditions

Insulin Sensitivity; Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

placebo, 2 tablets per day

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Patients received either placebo, metformin or rosiglitazone

Metformin

500mg 1 tablet 2 times per day for the first 2 weeks, then after that 2 tables 2 times per day

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

Patients received either placebo, metformin or rosiglitazone

Rosiglitazone

2 mg 1 tablets 2 times per day for the first 2 weeks, then after that 2 tablets 2 times per day

Group Type: ACTIVE_COMPARATOR

Rosiglitazone

Intervention Type: DRUG

Patients received either placebo, metformin or rosiglitazone

Interventions

Rosiglitazone

Patients received either placebo, metformin or rosiglitazone

Intervention Type: DRUG

Metformin

Patients received either placebo, metformin or rosiglitazone

Intervention Type: DRUG

Placebo

Patients received either placebo, metformin or rosiglitazone

Intervention Type: DRUG

Other Intervention Names

Avandia

Eligibility Criteria

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

SmithKline Beecham

INDUSTRY

Sponsor Role: collaborator

Turku University Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pirjo Nuutila, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Turku University Hospital

Locations

Turku PET Centre

Turku, Turku, Finland

Turku university hospital, PET center

Turku, Turku, Finland

Turku PET Centre (Turku University Hospital)

Turku, , Finland

Countries

Finland

References

Koffert JP, Mikkola K, Virtanen KA, Andersson AD, Faxius L, Hallsten K, Heglind M, Guiducci L, Pham T, Silvola JMU, Virta J, Eriksson O, Kauhanen SP, Saraste A, Enerback S, Iozzo P, Parkkola R, Gomez MF, Nuutila P. Metformin treatment significantly enhances intestinal glucose uptake in patients with type 2 diabetes: Results from a randomized clinical trial. Diabetes Res Clin Pract. 2017 Sep;131:208-216. doi: 10.1016/j.diabres.2017.07.015. Epub 2017 Jul 20.

Reference Type: DERIVED

PMID: 28778047 (View on PubMed)

Other Identifiers

TurkuUH-ROSI

Identifier Type: -

Identifier Source: org_study_id