A Study of the Co-administration of Sitagliptin and Atorvastatin in Inadequately Controlled Type 2 Diabetes Mellitus (MK-0431E-211)
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Sitagliptin; Atorvastatin; Placebo to sitagliptin; Placebo to atorvastatin; Metformin (open-label); Glimepiride (open-label); Glimepiride (double-blind); Placebo to glimepiride
Intervention description: Sitagliptin 100 mg tablet orally daily; Atorvastatin 80 mg tablet orally daily; Placebo to sitagliptin tablet orally daily; Placebo to atorvastatin tablet orally daily.; Participant will remain on prestudy dose of metformin tablets (at least 1500 mg daily) throughout entire study.; Phase A: Glimepiride 1 or 2 mg tablet once daily with breakfast or the first main meal of the day (titrated up to 6 mg/day) for 16 weeks as rescue therapy for randomized participants not meeting specific glycemic goals.; Phase B: glimepiride up to 6 mg daily for participants not rescued with open-label glimepiride during Phase A.; Phase B: placebo to glimepiride tablet orally daily.
Intervention MeSH terms: Metformin; Sitagliptin Phosphate; Glimepiride; Atorvastatin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 166.0
Sex: All
Minimum age: 18 Years
Maximum age: 79 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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