A Type 2 Diabetes Study of the Longer-Term Glycemic Effect of AVANDAMET vs. Metformin
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Avandamet 6 mg/1500 mg (ttd); Avandamet 4 mg/1000 mg (ttd); Avandamet 2 mg/500 mg (ttd); Avandamet 8 mg/ 2000 mg (ttd); Metformin 500 mg (ttd); Metformin 1000 mg (ttd); Metformin 1500 mg (ttd); Metformin 2000 mg (ttd)
Intervention description: 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; 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.; 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.; 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.; 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.; 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.; 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.; 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.
Intervention MeSH terms: Metformin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 688.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Fasting Plasma Glucose; Dual energy X ray absorptiometry (DXA); Drug-naive; Type 2 diabetes mellitus; Bone Mineral Density; Hyperglycemia; HbA1c

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The subject provides written informed consent.

          -  The subject is male or female and 18 to 75 years of age at the time of pre-screening.

          -  The subject has an established clinical diagnosis of type 2 diabetes according to
             recommended guidelines (e.g., American Diabetes Association, International Diabetes
             Federation, World Health Organization, Canadian Diabetes Association, or American
             Association of Clinical Endocrinologists).

          -  The subject is currently treated with diet and exercise, and has not taken more than 2
             weeks of an anti-diabetic monotherapy or insulin in the past 6 months.

          -  The subject has a BMI >25 kg/m2 at pre-screening.

          -  The subject has a Quest HbA1c 7.5% to 10.5% at pre-screening.

          -  The subject has a fasting capillary blood glucose 126 mg/dL (7mmol/L), as measured by
             the site staff at week 0.

          -  If the subject is a pre-menopausal female of child-bearing potential, she agrees to
             practice acceptable contraceptive measures (e.g. oral birth control pills, Norplant,
             Depo-Provera, an intrauterine device (IUD), a diaphragm with spermicide or a condom
             with spermicide, or abstinence) at least 1 month before screening, during the study,
             and for 30 days after the last dose of study medication is taken

          -  The subject is able and willing to perform self-monitoring of blood glucose as
             specified in this protocol.

        Exclusion Criteria:

          -  The subject has taken an oral anti-diabetic monotherapy or insulin for more than 14
             days in the past 6 months.

          -  The subject has presence of clinically significant renal or hepatic disease (serum
             creatinine 1.5 mg/dL (132.6 mol/L) for males and 1.4 mg/dL (123.8 mol/L) for females):
             ALT, AST, total bilirubin, or alkaline phosphatase >2.5 times the upper limit of the
             normal (ULN) reference range.

          -  The subject has anemia defined by hemoglobin concentration <11g/dL (110g/L) for males
             or <10g/dL (100g/L) for females.

          -  Presence of unstable or severe angina, coronary insufficiency or New York Heart
             Association (NYHA) class III-IV or any congestive heart failure requiring
             pharmacologic treatment.

          -  The subject has systolic blood pressure >160 mmHg or diastolic blood pressure >90 mmHg

          -  The subject has a chronic disease requiring intermittent or chronic treatment with
             oral, intravenous, or intra-articular corticosteroids (i.e., only use of topical,
             inhaled or nasal corticosteroids is permitted).

          -  The subject has acute or chronic metabolic acidosis or a history of diabetic
             ketoacidosis.

          -  The subject has a clinically significant abnormality which in the judgment of the
             investigator makes the subject unsuitable for inclusion in the study (e.g., physical
             examination, laboratory tests, or electrocardiogram, etc).

          -  The subject has used an investigational agent within 30 days or 5 half-lives
             (whichever was longer) prior to pre-screening.

          -  The subject is a female who is lactating, pregnant, or planned to become pregnant.

          -  The subject has a prior history of severe edema or a medically serious fluid related
             event (e.g., heart failure).

          -  The subject has a history of macular edema.

          -  The subject has significant hypersensitivity (e.g., difficulty swallowing, difficulty
             breathing, and tachycardia or skin reaction) to TZDs, biguanides, or compounds with
             similar chemical structures.

          -  The subject has a diagnosis of cancer (other than squamous, basal cell, or cervical
             cancer in-situ) in the past 3 years and is receiving treatment for cancer.

          -  The subject has a history or suspicion of drug abuse or alcohol abuse within the last
             6 months.

          -  The subject is known to have severe lactose intolerance.

          -  The subject is not willing to comply with visits and procedures described in the
             protocol.

          -  The subject has a disease that may affect bone turnover including, but not limited to:
             Paget's disease, hypercalcemia, hypocalcemia, hyperparathyroidism, hyperthyroidism,
             osteomalacia, metastatic bone disease

          -  The subject has a weight of greater than 300 lbs (136.4 kg).

          -  The subject has received treatment with bisphosphonates (≥1 month cumulative treatment
             within the last 12 months) or fluoride (dose greater than 10mg/day within the previous
             5 years).