Study In Postmenopausal Women With Type 2 Diabetes Looking At Approved Diabetes Drugs And How They Affect Bone Health

A 52 Week Randomized, Double-Blind, Multicenter, Mechanistic Study With a 24 Week Open-Label Follow-Up to Evaluate the Effect of AVANDIA TM on Bone in Postmenopausal Women With Type 2 Diabetes Mellitus

The purpose of this study is to determine the effects of rosiglitazone on the bone in postmenopausal women with type 2 diabetes mellitus

Inclusion Criteria:

• Female, >55 to <80 years
• >5 years menopausal
• Type 2 Diabetes Mellitus (T2DM) diagnosis according to American Diabetes Association (ADA), American Association of Clinical Endocrinologists (AACE), Canadian Diabetes Association (CDA), World Health Organization/International Diabetes Federation (WHO/IDF)
• Drug-naïve (HbA1c < or = 9.0%); OR Prior monotherapy, submaximal doses of metformin (< or = 1000mg Metformin), sulfonylureas (< or = 5mg Glyburide, < or = 10mg Glipizide or < or = 8mg glimepiride) or full dose Januvia (100mg) (HbA1c < or = 8.5%); OR Prior monotherapy, > submaximal doses of metformin (>1000mg) or sulfonylureas (>5mg Glyburide, >10mg Glipizide or >8mg glimepiride) (HbA1c < or = 7.0%)
• Weighs <300 lbs (136.4 kg)
• Two or more vertebra (L1-L4) suitable for BMD measurement by dual x-ray absorptiometry (DXA)
• Absolute BMD value consistent with T-score >-2.5 at femoral neck, lumbar spine and total hip

Exclusion Criteria:

• Type 1 Diabetes Mellitus (T1DM) or history of diabetic ketoacidosis (DKA)
• Renal or hepatic disease (clinically significant)
• Hepatocellular reaction, severe edema, or medically serious fluid event associated with thiazolidinedione (TZD)
• Recent (<6mos) history or clinical intervention for angina or myocardial infarction or is taking nitrates
• Any stage of heart failure, i.e. New York Heart Association (NYHA) class I-IV
• Systolic BP >160mmHg or diastolic BP >90mmHg while on antihypertensive
• Hypersensitivity to TZDs, biguanides
• Prior treatment with two or more oral anti-diabetic (OAD) agents
• Bilateral hip replacements
• Concurrent diseases affecting bone metabolism
• Active malabsorption syndrome
• Serum calcium outside the central lab reference range
• Thyroid replacement therapy, serum thyroid stimulating hormone (TSH) must be within range
• Vitamin D deficiency
• Previous treatment with: strontium, intravenous (IV) bisphosphonate, fluoride, hormones, calcineurin inhibitors or methotrexate
• Chronic systemic corticosteroid [e.g. glucocorticoid, mineralocorticoid] treatment of no more than two intra-articular injections within the past year or use of oral parenteral, or long-term, high-dose inhaled corticosteroids