Conditions: Diabetes Mellitus, Type 2
Keywords: Fasting Plasma Glucose Dual energy X ray absorptiometry (DXA) Drug-naive Type 2 diabetes mellitus Bone Mineral Density Hyperglycemia HbA1c
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 688
Healthy volunteers: no

Brief summary:
This study will evaluate the longer-term glycemic effect of two medicines approved for initial treatment of type 2 diabetes. The study consists of a 2 week screening period (2 study visits), followed by an 80 week double-blind treatment period (11 study visits). Also, a sub-study was included to look at changes in bone mineral density (BMD) at the lumbar spine.

Detailed description:
This was a phase IV, randomized, double-blind, global, multi-centre study. The study consisted of a 2 week screening period followed by an 80 week double-blind treatment period. Subjects who met all eligibility requirements were randomized in a 1:1 ratio, stratified by country, gender (male and female) and pre-screening HbA1c (≤9% or\>9) either to MET or AVM. When the substudy was added, a new randomization was created for the participating centers. Those subjects in the bone sub-study were stratified by country, gender (male, premenopausal female, and postmenopausal female), pre-screening HbA1c (i.e., ≤9%; \>9%), and either to MET or AVM.

At randomization, Visit 3 (Week 0), subjects were initiated at Dose Level 1. Treatment with AVM was initiated at a dose of 4 mg/500 mg and titrated up to a maximum total daily dose of AVM 8 mg/2000 mg. Treatment with MET therapy was initiated at a dose of 500 mg and titrated up to a maximum daily dose of 2000mg.

Arms:
arm 1: MET began at a total daily dose of 500 mg and could be increased up to a maximum dose of MET 2000 mg. The dose level was to be increased unless a tolerability issue existed at the current dose level. arm 2: AVM began at a total daily dose of 4 mg/500 mg and could be increased up to a maximum dose of AVM 8 mg/2000 mg

Interventions: intervention 1: Avandamet 6 mg/1500 mg (ttd) intervention 2: Avandamet 4 mg/1000 mg (ttd) intervention 3: Avandamet 2 mg/500 mg (ttd) intervention 4: Avandamet 8 mg/ 2000 mg (ttd) intervention 5: Metformin 500 mg (ttd) intervention 6: Metformin 1000 mg (ttd) intervention 7: Metformin 1500 mg (ttd) intervention 8: Metformin 2000 mg (ttd)
Intervention descriptions: intervention 1: One 2 mg/ 500 mg capsule will be taken in the AM with the morning meal Two 2 mg/ 500 mg capsules will be taken in the PM with the evening meal intervention 2: One 2 mg/500 mg capsule will be taken in the AM with the morning meal. One 2 mg/500 mg capsule will be taken in the PM with the evening meal. intervention 3: one placebo capsule will be taken in the AM with the morning meal one 2 mg/ 500 mg capsule will be taken in the PM with the evening meal. intervention 4: Two 2 mg/ 500 mg capsules will be taken in the AM with the morning meal. Two 2 mg/ 500 mg capsules will be taken in the PM with the evening meal. intervention 5: One placebo capsule will be taken in the AM with the morning meal. One 500 mg capsule will be taken in the PM with the evening meal. intervention 6: One 500 mg capsule will be taken in the AM with the morning meal. One 500 mg capsule will be taken in the PM with the evening meal. intervention 7: One 500 mg capsule will be taken in the AM with the morning meal. Two 500 mg capsules will be taken in the PM with the evening meal. intervention 8: Two 500 mg capsule will be taken in the AM with the morning meal. Two 500 mg capsule will be taken in the PM with the evening meal.

Protocol document: