a type 2 diabetes study of the longer-term glycemic effect of avandamet vs. metformin

Conditions: Diabetes Mellitus, Type 2

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.

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.

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).

Keywords: fasting plasma glucose dual energy x ray absorptiometry (dxa) drug-naive type 2 diabetes mellitus bone mineral density hyperglycemia hba1c