A Study of the Co-administration of Sitagliptin and Atorvastatin in Inadequately Controlled Type 2 Diabetes Mellitus (MK-0431E-211)

A Phase III Randomized Clinical Trial to Study the Efficacy and Safety of the Co-administration of Sitagliptin and Atorvastatin in Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Monotherapy

This two-phase study was to examine if 16 weeks of treatment with sitagliptin in combination with atorvastatin reduces hemoglobin A1C (A1C) and low density lipoprotein cholesterol (LDL-C) from baseline more than atorvastatin alone and sitagliptin alone, respectively. Following a single-blind placebo run-in period, participants were to be randomized to one of three treatment arms (sitagliptin monotherapy, atorvastatin monotherapy, or sitagliptin plus atorvastatin) for 16 weeks (Phase A). During Phase B of the study (Weeks 16 through 54), participants were to receive either sitagliptin plus atorvastatin or glimepiride plus atorvastatin. The primary hypotheses were that after 16 weeks of treatment, sitagliptin in combination with atorvastatin reduces A1C from baseline more than atorvastatin alone, and that atorvastatin in combination with sitagliptin lowers LDL-C from baseline more than sitagliptin alone.

Inclusion Criteria:

• has type 2 diabetes mellitus
• is a male, or a female who is highly unlikely to conceive
• is currently on monotherapy with metformin (at least 1500 mg/day) for at least 8 weeks
• is not on statin therapy or other lipid-lowering agents for at least 6 weeks

Exclusion Criteria:

• has a history of type 1 diabetes mellitus, ketoacidosis or possibly has type 1 diabetes
• has ever taken a dipeptidyl peptidase IV inhibitor (such as sitagliptin, vildagliptin, alogliptin, or saxagliptin) or a glucagon-like peptide-1 mimetic (such as exenatide or liraglutide), or has required insulin therapy within 12 weeks prior to signing informed consent
• has been on a peroxisome proliferator-activated receptor gamma agonist within the prior 12 weeks
• has been treated with a statin or other lipid-lowering agents, including over the counter supplements of fish oils within 6 weeks
• intends to consume at least 1.2 liters of grapefruit juice per day during the course of the study
• is on or is likely to require treatment with 14 consecutive days or more, or repeated courses of corticosteroids
• is on a weight loss program and not in the maintenance phase or has started a weight loss medication (such as orlistat or sibutramine) within the prior 8 weeks
• has undergone a surgical procedure within the prior 4 weeks
• has a history of myopathy or rhabdomyolysis with any statin.
• has cardiovascular disease
• has New York Heart Association (NYHA) Class III or IV congestive heart failure, inadequately controlled hypertension, a medical history of active liver disease, chronic progressive neuromuscular disorder, is human immunodeficiency virus (HIV) positive, has a clinically significant hematological disorder, uncontrolled endocrine or metabolic disease known to influence glycemic control or serum lipids/lipoproteins, untreated hyperthyroidism or is currently under treatment for hyperthyroidism
• has a history of malignancy within 5 years, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
• is pregnant or breastfeeding, or is intending to become pregnant or donate eggs within the projected duration of the study and post-study follow-up period
• uses recreational or illicit drugs or has had a recent history (within the last year) of drug abuse or increased alcohol consumption