A Study of the Co-administration of Sitagliptin and Atorvastatin in Inadequately Controlled Type 2 Diabetes Mellitus (MK-0431E-211)
- Conditions
- Type 2 Diabetes Mellitus
- Interventions
- Other: Placebo to sitagliptinOther: Placebo to atorvastatin
- Registration Number
- NCT01477853
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 166
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sitagliptin/Sitagliptin + Atorvastatin Sitagliptin In Phase A, participants received sitagliptin 100 mg plus matching placebo to atorvastatin daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks. Sitagliptin/Sitagliptin + Atorvastatin Placebo to atorvastatin In Phase A, participants received sitagliptin 100 mg plus matching placebo to atorvastatin daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks. Sitagliptin/Sitagliptin + Atorvastatin Metformin (open-label) In Phase A, participants received sitagliptin 100 mg plus matching placebo to atorvastatin daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks. Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin Metformin (open-label) In Phase A, participants sitagliptin 100 mg plus atorvastatin 80 mg daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks. Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin Glimepiride (open-label) In Phase A, participants sitagliptin 100 mg plus atorvastatin 80 mg daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks. Sitagliptin/Sitagliptin + Atorvastatin Glimepiride (open-label) In Phase A, participants received sitagliptin 100 mg plus matching placebo to atorvastatin daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks. Sitagliptin/Sitagliptin + Atorvastatin Placebo to glimepiride In Phase A, participants received sitagliptin 100 mg plus matching placebo to atorvastatin daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks. Atorvastatin/Atorvastatin + Glimepiride Atorvastatin In Phase A, participants received atorvastatin 80 mg plus matching placebo to sitagliptin daily for 16 weeks. Participants continuing to Phase B received atorvastatin 80 mg plus matching placebo to sitagliptin plus glimepiride daily for an additional 38 weeks. Atorvastatin/Atorvastatin + Glimepiride Placebo to sitagliptin In Phase A, participants received atorvastatin 80 mg plus matching placebo to sitagliptin daily for 16 weeks. Participants continuing to Phase B received atorvastatin 80 mg plus matching placebo to sitagliptin plus glimepiride daily for an additional 38 weeks. Atorvastatin/Atorvastatin + Glimepiride Metformin (open-label) In Phase A, participants received atorvastatin 80 mg plus matching placebo to sitagliptin daily for 16 weeks. Participants continuing to Phase B received atorvastatin 80 mg plus matching placebo to sitagliptin plus glimepiride daily for an additional 38 weeks. Atorvastatin/Atorvastatin + Glimepiride Glimepiride (double-blind) In Phase A, participants received atorvastatin 80 mg plus matching placebo to sitagliptin daily for 16 weeks. Participants continuing to Phase B received atorvastatin 80 mg plus matching placebo to sitagliptin plus glimepiride daily for an additional 38 weeks. Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin Sitagliptin In Phase A, participants sitagliptin 100 mg plus atorvastatin 80 mg daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks. Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin Placebo to glimepiride In Phase A, participants sitagliptin 100 mg plus atorvastatin 80 mg daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks. Sitagliptin/Sitagliptin + Atorvastatin Atorvastatin In Phase A, participants received sitagliptin 100 mg plus matching placebo to atorvastatin daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks. Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin Atorvastatin In Phase A, participants sitagliptin 100 mg plus atorvastatin 80 mg daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks.
- Primary Outcome Measures
Name Time Method Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 16 Baseline and Week 16 Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.
Number of Participants Who Experienced at Least One Adverse Event Up to 56 weeks (including 2-week follow-up) An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the investigational product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the investigational product, is also an adverse event. Data presented exclude data following the initiation of glycemic rescue therapy.
Number of Participants Who Discontinued Study Drug Due to an Adverse Event Up to 54 weeks An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the investigational product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the investigational product, is also an adverse event. Data presented exclude data following the initiation of glycemic rescue therapy.
Change From Baseline in Hemoglobin A1C (A1C) at Week 16 Baseline and Week 16 A1C is measured as percent. Thus, this change from baseline reflects the Week 16 A1C percent minus the Week 0 A1C percent.
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16 Baseline and Week 16 Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.
Percent Change From Baseline in Non-high Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16 Baseline and Week 16 Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16 Baseline and Week 16 Change from baseline reflects the Week 16 value minus the Week 0 value.
Percent Change From Baseline in Total Cholesterol at Week 16 Baseline and Week 16 Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.
Percent Change From Baseline in Triglycerides at Week 16 Baseline and Week 16 Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.
Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at Week 16 Baseline and Week 16 Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 16 Baseline and Week 16 Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.