Clinical trial NCT02526615: Effects of Rosiglitazone and Metformin on Metabolism in Type 2 Diabetes
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Insulin Sensitivity
Type 2 Diabetes
Keywords: rosiglitazone
metformin
muscle
Lead sponsor: Turku University Hospital
Sponsor class: OTHER_GOV
Collaborators: name: SmithKline Beecham
First posted: 2015-08-18
Enrollment: 48
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: insulin sensitivity in skeletal muscle
timeFrame: 26 weeks
Secondary outcomes:
measure: skeletal muscle blood flow
timeFrame: 26 weeks
measure: insulin signaling pathways in skeletal muscle
timeFrame: 26 weeks
measure: insulin sensitivity of bone marrow fat
timeFrame: 26 weeks
measure: insulin stimulated intestinal glucose uptake
timeFrame: 26 weeks
Other outcomes:
Locations:
city: Turku
country: Finland
facility: Turku PET Centre
city: Turku
country: Finland
facility: Turku university hospital, PET center
city: Turku
country: Finland
facility: Turku PET Centre (Turku University Hospital)
Study officials:
affiliation: Turku University Hospital
name: Pirjo Nuutila, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.