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TerminatedNCT01477853Updated Jul 26, 2018Results posted

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

A Phase 3 interventional study of Sitagliptin and Atorvastatin in Type 2 Diabetes Mellitus, sponsored by Merck Sharp & Dohme LLC. Terminated. Open to participants aged 18 Years to 79 Years. Per ClinicalTrials.gov, last updated 2018-07-26.

Sponsored by Merck Sharp & Dohme LLC · Phase 3, Interventional, and Treatment

Why this study was terminated
The study was terminated early by the Sponsor for business reasons.
Phase
Phase 3
Study type
Interventional
Enrollment
166
Allocation
Randomized
Ages
18 Years to 79 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Type 2 Diabetes Mellitus
03

In context

Diabetes Mellitus

10,925 studies on the registry are indexed under Diabetes Mellitus; 1,319 are open to participants now.

This study's enrollment of 166 is above the median of 80 across 8,367 interventional studies indexed under Diabetes Mellitus.

Browse Diabetes Mellitus studies →

Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 79 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
166 participants (actual)

Study arms

  • Experimental
    Sitagliptin/Sitagliptin + 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.

    Drug: Sitagliptin · Drug: Atorvastatin · Other: Placebo to atorvastatin · Drug: Metformin (open-label) · Drug: Glimepiride (open-label) · Drug: Placebo to glimepiride

  • Active comparator
    Atorvastatin/Atorvastatin + Glimepiride

    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.

    Drug: Atorvastatin · Other: Placebo to sitagliptin · Drug: Metformin (open-label) · Drug: Glimepiride (double-blind)

  • Experimental
    Sitagliptin + Atorvastatin/Sitagliptin + 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.

    Drug: Sitagliptin · Drug: Atorvastatin · Drug: Metformin (open-label) · Drug: Glimepiride (open-label) · Drug: Placebo to glimepiride

Interventions

  • DrugSitagliptin

    Sitagliptin 100 mg tablet orally daily

    Also known as: Januvia

  • DrugAtorvastatin

    Atorvastatin 80 mg tablet orally daily

    Also known as: Lipitor

  • OtherPlacebo to sitagliptin

    Placebo to sitagliptin tablet orally daily

  • OtherPlacebo to atorvastatin

    Placebo to atorvastatin tablet orally daily.

  • DrugMetformin (open-label)

    Participant will remain on prestudy dose of metformin tablets (at least 1500 mg daily) throughout entire study.

    Also known as: Glucophage

  • DrugGlimepiride (open-label)

    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.

    Also known as: Amaryl

  • DrugGlimepiride (double-blind)

    Phase B: glimepiride up to 6 mg daily for participants not rescued with open-label glimepiride during Phase A.

  • DrugPlacebo to glimepiride

    Phase B: placebo to glimepiride tablet orally daily.

06

What researchers measure

Primary outcomes

  1. Change From Baseline in Hemoglobin A1C (A1C) at Week 16

    A1C is measured as percent. Thus, this change from baseline reflects the Week 16 A1C percent minus the Week 0 A1C percent.

    Time frame: Baseline and Week 16

  2. Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at 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%.

    Time frame: Baseline and Week 16

  3. Number of Participants Who Experienced at Least One Adverse Event

    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.

    Time frame: Up to 56 weeks (including 2-week follow-up)

  4. Number of Participants Who Discontinued Study Drug Due to an Adverse Event

    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.

    Time frame: Up to 54 weeks

Secondary outcomes

  1. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16

    Change from baseline reflects the Week 16 value minus the Week 0 value.

    Time frame: Baseline and Week 16

  2. Percent Change From Baseline in Total Cholesterol at 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%.

    Time frame: Baseline and Week 16

  3. Percent Change From Baseline in Apolipoprotein B (Apo B) at 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%.

    Time frame: Baseline and Week 16

  4. Percent Change From Baseline in Non-high Density Lipoprotein Cholesterol (Non-HDL-C) at 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%.

    Time frame: Baseline and Week 16

  5. Percent Change From Baseline in Triglycerides at 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%.

    Time frame: Baseline and Week 16

  6. Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at 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%.

    Time frame: Baseline and Week 16

  7. Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at 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%.

    Time frame: Baseline and Week 16

07

Results

Posted Oct 5, 2016
Limitations and caveats
The study was terminated early by the Sponsor for business reasons. Due to the small number of participants included in the FAS, the results for Phase A and for the overall study should be interpreted with caution.

Participant flow

Note: 10 participants were enrolled in the study more than once (at more than 1 study site). Nine participants were enrolled twice and one participant was randomized at 3 different sites. Therefore, data of 10 actual participants (counted as 21 participants due to multiple screening/randomization) were removed from the efficacy analyses.

Phase A
Participant flow — Phase A
MilestoneSitagliptin/Sitagliptin + AtorvastatinAtorvastatin/Atorvastatin + GlimepirideSitagliptin + Atorvastatin/Sitagliptin + Atorvastatin
Started555655
Completed121111
Not completed434544
Withdrew: Adverse event122
Withdrew: Lost to follow-up432
Withdrew: Physician decision101
Withdrew: Study terminated by sponsor374039
Phase B
Participant flow — Phase B
MilestoneSitagliptin/Sitagliptin + AtorvastatinAtorvastatin/Atorvastatin + GlimepirideSitagliptin + Atorvastatin/Sitagliptin + Atorvastatin
Started121111
Completed000
Not completed121111
Withdrew: Lost to follow-up010
Withdrew: Study terminated by sponsor121011

Outcome measures

PrimaryChange From Baseline in Hemoglobin A1C (A1C) at Week 16

A1C is measured as percent. Thus, this change from baseline reflects the Week 16 A1C percent minus the Week 0 A1C percent.

Time frame:
Baseline and Week 16
Reported as:
Mean · Percent
Change From Baseline in Hemoglobin A1C (A1C) at Week 16
PercentSitagliptin/Sitagliptin + AtorvastatinAtorvastatin/Atorvastatin + GlimepirideSitagliptin + Atorvastatin/Sitagliptin + Atorvastatin
Change From Baseline in Hemoglobin A1C (A1C) at Week 16-1.17 ± 0.200.04 ± 0.31-1.01 ± 0.22
PrimaryPercent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at 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%.

Time frame:
Baseline and Week 16
Reported as:
Mean · Percent change
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 16
Percent changeSitagliptin/Sitagliptin + AtorvastatinAtorvastatin/Atorvastatin + GlimepirideSitagliptin + Atorvastatin/Sitagliptin + Atorvastatin
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 164.9 ± 10.4-35.7 ± 7.1-38.7 ± 6.6
SecondaryChange From Baseline in Fasting Plasma Glucose (FPG) at Week 16

Change from baseline reflects the Week 16 value minus the Week 0 value.

Time frame:
Baseline and Week 16
Reported as:
Mean · mg/dL
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16
mg/dLSitagliptin/Sitagliptin + AtorvastatinAtorvastatin/Atorvastatin + GlimepirideSitagliptin + Atorvastatin/Sitagliptin + Atorvastatin
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16-15.7 ± 6.422.7 ± 10.1-26.0 ± 14.0
SecondaryPercent Change From Baseline in Total Cholesterol at 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%.

Time frame:
Baseline and Week 16
Reported as:
Mean · Percent change
Percent Change From Baseline in Total Cholesterol at Week 16
Percent changeSitagliptin/Sitagliptin + AtorvastatinAtorvastatin/Atorvastatin + GlimepirideSitagliptin + Atorvastatin/Sitagliptin + Atorvastatin
Percent Change From Baseline in Total Cholesterol at Week 16-1.7 ± 6.2-28.3 ± 4.8-25.7 ± 6.0
SecondaryPercent Change From Baseline in Apolipoprotein B (Apo B) at 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%.

Time frame:
Baseline and Week 16
Reported as:
Mean · Percent change
Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16
Percent changeSitagliptin/Sitagliptin + AtorvastatinAtorvastatin/Atorvastatin + GlimepirideSitagliptin + Atorvastatin/Sitagliptin + Atorvastatin
Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16-4.8 ± 6.5-32.9 ± 5.6-29.0 ± 4.6
SecondaryPercent Change From Baseline in Non-high Density Lipoprotein Cholesterol (Non-HDL-C) at 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%.

Time frame:
Baseline and Week 16
Reported as:
Mean · Percent change
Percent Change From Baseline in Non-high Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16
Percent changeSitagliptin/Sitagliptin + AtorvastatinAtorvastatin/Atorvastatin + GlimepirideSitagliptin + Atorvastatin/Sitagliptin + Atorvastatin
Percent Change From Baseline in Non-high Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16-1.0 ± 8.8-34.4 ± 6.7-34.6 ± 6.7
SecondaryPercent Change From Baseline in Triglycerides at 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%.

Time frame:
Baseline and Week 16
Reported as:
Mean · Percent change
Percent Change From Baseline in Triglycerides at Week 16
Percent changeSitagliptin/Sitagliptin + AtorvastatinAtorvastatin/Atorvastatin + GlimepirideSitagliptin + Atorvastatin/Sitagliptin + Atorvastatin
Percent Change From Baseline in Triglycerides at Week 16-9.9 ± 8.6-28.7 ± 6.5-10.5 ± 13.5
SecondaryPercent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at 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%.

Time frame:
Baseline and Week 16
Reported as:
Mean · Percent change
Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at Week 16
Percent changeSitagliptin/Sitagliptin + AtorvastatinAtorvastatin/Atorvastatin + GlimepirideSitagliptin + Atorvastatin/Sitagliptin + Atorvastatin
Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at Week 16-15.5 ± 7.2-28.6 ± 6.6-10.4 ± 13.5
SecondaryPercent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at 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%.

Time frame:
Baseline and Week 16
Reported as:
Mean · Percent change
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 16
Percent changeSitagliptin/Sitagliptin + AtorvastatinAtorvastatin/Atorvastatin + GlimepirideSitagliptin + Atorvastatin/Sitagliptin + Atorvastatin
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 16-0.3 ± 3.2-5.8 ± 3.51.5 ± 6.0
PrimaryNumber of Participants Who Experienced at Least One Adverse Event

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.

Time frame:
Up to 56 weeks (including 2-week follow-up)
Reported as:
Number · Participants
Number of Participants Who Experienced at Least One Adverse Event
ParticipantsSitagliptin/Sitagliptin + AtorvastatinAtorvastatin/Atorvastatin + GlimepirideSitagliptin + Atorvastatin/Sitagliptin + Atorvastatin
Number of Participants Who Experienced at Least One Adverse Event101313
PrimaryNumber of Participants Who Discontinued Study Drug Due to an Adverse Event

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.

Time frame:
Up to 54 weeks
Reported as:
Number · Participants
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
ParticipantsSitagliptin/Sitagliptin + AtorvastatinAtorvastatin/Atorvastatin + GlimepirideSitagliptin + Atorvastatin/Sitagliptin + Atorvastatin
Number of Participants Who Discontinued Study Drug Due to an Adverse Event122

Adverse events

Collected over Up to 56 weeks including 2-week follow-up (up to 56 weeks for serious adverse events, up to 54 weeks for non-serious adverse events). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Sitagliptin/Sitagliptin + Atorvastatin—0/55 (0%)3/55 (5.5%)
Atorvastatin/Atorvastatin + Glimepiride—0/56 (0%)3/56 (5.4%)
Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin—1/55 (1.8%)5/55 (9.1%)
Most frequent serious events
Most frequent serious events
EventSitagliptin/Sitagliptin + AtorvastatinAtorvastatin/Atorvastatin + GlimepirideSitagliptin + Atorvastatin/Sitagliptin + Atorvastatin
Inguinal herniaGastrointestinal disorders0/550/561/55
Most frequent other events
Most frequent other events
EventSitagliptin/Sitagliptin + AtorvastatinAtorvastatin/Atorvastatin + GlimepirideSitagliptin + Atorvastatin/Sitagliptin + Atorvastatin
Glomerular filtration rate decreasedInvestigations1/550/563/55
Intentional overdoseInjury, poisoning and procedural complications2/553/562/55

Baseline characteristics

Age, Continuous
Age, Continuous(Years)Sitagliptin/Sitagliptin + AtorvastatinAtorvastatin/Atorvastatin + GlimepirideSitagliptin + Atorvastatin/Sitagliptin + AtorvastatinTotal
Mean56.2 ± 9.756.3 ± 8.253.7 ± 10.055.4 ± 9.4
Sex: Female, Male
Sex: Female, Male(Participants)Sitagliptin/Sitagliptin + AtorvastatinAtorvastatin/Atorvastatin + GlimepirideSitagliptin + Atorvastatin/Sitagliptin + AtorvastatinTotal
Female24272475
Male31293191
08

Study locations

No study locations are listed for this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 26, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01477853
Lead sponsor
Merck Sharp & Dohme LLC
Responsible party
Sponsor
First posted
Nov 23, 2011
Start date
Oct 24, 2011
Primary completion
Dec 4, 2012
Completion
Dec 4, 2012
Results posted
Oct 5, 2016
Last update
Jul 26, 2018

Study contacts

Medical Director
study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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