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CompletedNCT00350779Updated May 12, 2017Results posted

Sitagliptin Metformin/PPARg Agonist Combination Therapy Add-on (0431-052)

A Phase 3 interventional study of sitagliptin and Comparator: Placebo in Type 2 Diabetes Mellitus, sponsored by Merck Sharp & Dohme LLC. Completed. Open to participants aged 18 Years to 78 Years. Per ClinicalTrials.gov, last updated 2017-05-12.

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

Phase
Phase 3
Study type
Interventional
Enrollment
262
Allocation
Randomized
Ages
18 Years to 78 Years
Sex
All
01

Study summary

A clinical study to determine the safety and efficacy of sitagliptin in patients with Type 2 Diabetes Mellitus who have inadequate glycemic control on metformin/peroxisome proliferator-activated receptor gamma (PPARg) agonist combination therapy.

02

Conditions studied

  • Type 2 Diabetes Mellitus

Keywords

  • Type 2 Diabetes Mellitus
03

In context

Diabetes Mellitus

10,925 studies on the registry are indexed under Diabetes Mellitus; 1,318 are open to participants now.

This study's enrollment of 262 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 78 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Patient has type 2 diabetes mellitus
  • Patient is inadequately controlled while taking two oral antidiabetic medications

Exclusion criteria

Exclusion Criteria:

  • Patient has a history of type 1 diabetes mellitus or history of ketoacidosis
  • Patient required insulin therapy within the prior 3 months
  • Patient has been taking Byetta (R) (exenatide) within the prior 3 months
05

Study design

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

Study arms

  • Experimental
    1

    Sitagliptin

    Drug: sitagliptin · Drug: rosiglitazone · Drug: metformin · Drug: glipizide

  • Placebo comparator
    2

    Placebo

    Drug: Comparator: Placebo · Drug: rosiglitazone · Drug: metformin · Drug: glipizide

Interventions

  • Drugsitagliptin

    Sitagliptin 100mg tablet each day for 54 weeks. All subjects will be given placebo to sitagliptin for a 2 week period.

    Also known as: Januvia

  • DrugComparator: Placebo

    Placebo to sitagliptin 100mg tablet each day for 54 weeks.

  • Drugrosiglitazone

    Subjects taking 4mg or greater rosiglitazone at screening will enter a 6 week stable dose period followed by a 54 week treatment period. Subjects who are taking less than 4mg/day or no rosiglitazone at screening will be titrated to a stable dose of at least 4mg over a a maximum of 8 weeks followed by a dose stable period of up to 12 weeks then a 54 week treatment period. Total treatment will be up to 77 weeks.

    Also known as: Avandia

  • Drugmetformin

    Subjects taking 1500mg or greater metformin at screening will enter a 6 week stable dose period followed by a 54 week treatment period. Subjects who are taking less than 1500mg/day or no metformin at screening will be titrated to a stable dose of at least 1500mg over a a maximum of 8 weeks followed by a dose stable period of up to 12 weeks then a 54 week treatment period. Total treatment will be up to 77 weeks.

  • Drugglipizide

    Subjects not meeting specific glycemic controls during the 54-week treatment period will use glipizide as rescue therapy. Glipizide will be titrated in 5mg doses up to a maximum 40mg each day. (In Canada, the rescue therapy will be a sulfonylurea agent marketed in that country.)

    Also known as: Glucotrol

06

What researchers measure

Primary outcomes

  1. Change From Baseline in HbA1c (Hemoglobin A1C) at Week 18

    HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent.

    Time frame: Baseline and 18 Weeks

Secondary outcomes

  1. Change From Baseline in FPG (Fasting Plasma Glucose) at Week 18

    Change from baseline at Week 18 is defined as Week 18 minus Week 0

    Time frame: Baseline and 18 Weeks

  2. Change From Baseline in 2-hour PMG (Post-meal Glucose) at Week 18

    Change from baseline at Week 18 is defined as Week 18 minus Week 0

    Time frame: Baseline and Week 18

  3. Change From Baseline in HbA1c (Hemoglobin A1C) at Week 54

    HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 54 HbA1c percent minus the Week 0 HbA1c percent.

    Time frame: Baseline and Week 54

  4. Change From Baseline in FPG (Fasting Plasma Glucose) at Week 54

    Change from baseline at Week 54 is defined as Week 54 minus Week 0

    Time frame: Baseline and Week 54

  5. Change From Baseline in 2-hour PMG (Post-meal Glucose) at Week 54

    Change from baseline at Week 54 is defined as Week 54 minus Week 0.

    Time frame: Baseline and Week 54

07

Results

Posted Jul 3, 2009
Limitations and caveats
Non-serious adverse event results represent those events included in the primary safety analysis for this study (events occurred prior to initiation of glycemic rescue therapy). Site 0520039 was non-compliant with GDP, data was removed from analyses.

Participant flow

Phase III First Patient In: 29-Aug-06. Last Patient Enrolled: 23-Mar-07. Last Patient Last Visit: 27-May-08; 41 study centers worldwide

Participant flow — Overall Study
MilestoneSitagliptin 100 mgPlacebo
Started17092
Completed14871
Not completed2221
Withdrew: Adverse event42
Withdrew: Lack of efficacy04
Withdrew: Lost to follow-up20
Withdrew: Physician decision24
Withdrew: Protocol violation31
Withdrew: Withdrawal by subject98
Withdrew: Patient moved21
Withdrew: Non-compliance with study procedures01

Outcome measures

PrimaryChange From Baseline in HbA1c (Hemoglobin A1C) at Week 18

HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent.

Time frame:
Baseline and 18 Weeks
Reported as:
Least squares mean · Percent
Change From Baseline in HbA1c (Hemoglobin A1C) at Week 18
PercentSitagliptin 100 mgPlacebo
Change From Baseline in HbA1c (Hemoglobin A1C) at Week 18-1.03 (-1.17 to -0.90)-0.31 (-0.50 to -0.13)
Statistical analysis
  • Sitagliptin 100 mg vs Placebo · ANCOVA · p = <0.001 · Mean difference (net): -0.72 · 95% CI -0.95 to -0.49Model terms: treatment; baseline; prior anti-hyperglycemic therapy
SecondaryChange From Baseline in FPG (Fasting Plasma Glucose) at Week 18

Change from baseline at Week 18 is defined as Week 18 minus Week 0

Time frame:
Baseline and 18 Weeks
Reported as:
Least squares mean · mg/dL
Change From Baseline in FPG (Fasting Plasma Glucose) at Week 18
mg/dLSitagliptin 100 mgPlacebo
Change From Baseline in FPG (Fasting Plasma Glucose) at Week 18-30.7 (-35.5 to -26.0)-11.7 (-18.3 to -5.1)
Statistical analysis
  • Sitagliptin 100 mg vs Placebo · ANCOVA · p = <0.001 · Mean difference (net): -19.0 · 95% CI -27.2 to -10.9Model terms: treatment; baseline; prior anti-hyperglycemic therapy
SecondaryChange From Baseline in 2-hour PMG (Post-meal Glucose) at Week 18

Change from baseline at Week 18 is defined as Week 18 minus Week 0

Time frame:
Baseline and Week 18
Reported as:
Least squares mean · mg/dL
Change From Baseline in 2-hour PMG (Post-meal Glucose) at Week 18
mg/dLSitagliptin 100 mgPlacebo
Change From Baseline in 2-hour PMG (Post-meal Glucose) at Week 18-59.9 (-67.1 to -52.6)-22.0 (-32.1 to -12.0)
Statistical analysis
  • Sitagliptin 100 mg vs Placebo · ANCOVA · p = <0.001 · Mean difference (net): -37.9 · 95% CI -50.2 to -25.5Model terms: treatment; baseline; prior anti-hyperglycemic therapy
SecondaryChange From Baseline in HbA1c (Hemoglobin A1C) at Week 54

HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 54 HbA1c percent minus the Week 0 HbA1c percent.

Time frame:
Baseline and Week 54
Reported as:
Least squares mean · Percent
Change From Baseline in HbA1c (Hemoglobin A1C) at Week 54
PercentSitagliptin 100 mgPlacebo
Change From Baseline in HbA1c (Hemoglobin A1C) at Week 54-1.05 (-1.21 to -0.89)-0.28 (-0.50 to -0.05)
Statistical analysis
  • Sitagliptin 100 mg vs Placebo · ANCOVA · p = <0.001 · Mean difference (net): -0.77 · 95% CI -1.04 to -0.50Model terms: treatment; baseline; prior anti-hyperglycemic therapy
SecondaryChange From Baseline in FPG (Fasting Plasma Glucose) at Week 54

Change from baseline at Week 54 is defined as Week 54 minus Week 0

Time frame:
Baseline and Week 54
Reported as:
Least squares mean · mg/dL
Change From Baseline in FPG (Fasting Plasma Glucose) at Week 54
mg/dLSitagliptin 100 mgPlacebo
Change From Baseline in FPG (Fasting Plasma Glucose) at Week 54-28.0 (-33.3 to -22.8)-10.7 (-18.0 to -3.3)
Statistical analysis
  • Sitagliptin 100 mg vs Placebo · ANCOVA · p = <0.001 · Mean difference (net): -17.4 · 95% CI -26.4 to -8.4Model terms: treatment; baseline; prior anti-hyperglycemic therapy
SecondaryChange From Baseline in 2-hour PMG (Post-meal Glucose) at Week 54

Change from baseline at Week 54 is defined as Week 54 minus Week 0.

Time frame:
Baseline and Week 54
Reported as:
Least squares mean · mg/dL
Change From Baseline in 2-hour PMG (Post-meal Glucose) at Week 54
mg/dLSitagliptin 100 mgPlacebo
Change From Baseline in 2-hour PMG (Post-meal Glucose) at Week 54-50.7 (-59.1 to -42.4)-16.6 (-28.2 to -5.0)
Statistical analysis
  • Sitagliptin 100 mg vs Placebo · ANCOVA · p = <0.001 · Mean difference (net): -34.1 · 95% CI -48.4 to -19.9Model terms: treatment; baseline; prior anti-hyperglycemic therapy

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Sitagliptin 100 mg Data Through Week 18———
Placebo Data Through Week 18———
Sitagliptin 100 mg Data Through Week 54———
Placebo Data Through Week 54———
Most frequent serious events
Showing 10 of 26
Most frequent serious events
EventSitagliptin 100 mg Data Through Week 18Placebo Data Through Week 18Sitagliptin 100 mg Data Through Week 54Placebo Data Through Week 54
Any Neoplasms Benign, Malignant And UnspecifiedNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/1701/924/1702/92
Any Musculoskeletal And Connective Tissue DisordersMusculoskeletal and connective tissue disorders1/1700/923/1700/92
Any Cardiac DisordersCardiac disorders0/1700/922/1700/92
Myocardial InfarctionCardiac disorders0/1700/922/1700/92
Intervertebral Disc ProtrusionMusculoskeletal and connective tissue disorders1/1700/922/1700/92
Any Nervous System DisordersNervous system disorders0/1700/922/1700/92
Any Injury, Poisoning And Procedural ComplicationsInjury, poisoning and procedural complications0/1700/920/1701/92
Lower Limb FractureInjury, poisoning and procedural complications0/1700/920/1701/92
Astrocytoma MalignantNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/1700/920/1701/92
Basal Cell CarcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/1701/921/1701/92
Most frequent other events
Showing 10 of 14
Most frequent other events
EventSitagliptin 100 mg Data Through Week 18Placebo Data Through Week 18Sitagliptin 100 mg Data Through Week 54Placebo Data Through Week 54
Any Infections And InfestationsInfections and infestations20/17010/9246/17015/92
Upper Respiratory Tract InfectionInfections and infestations10/1706/9228/1706/92
NasopharyngitisInfections and infestations10/1704/9218/1709/92
Any General Disorders And Administration Site ConditionsGeneral disorders0/1700/9215/1705/92
Oedema PeripheralGeneral disorders0/1700/9215/1705/92
Any Nervous System DisordersNervous system disorders0/1700/9214/1708/92
Any Respiratory, Thoracic And Mediastinal DisordersNervous system disorders0/1700/927/1707/92
CoughRespiratory, thoracic and mediastinal disorders0/1700/927/1707/92
HeadacheNervous system disorders0/1700/9210/1704/92
Any Gastrointestinal DisordersGastrointestinal disorders0/1700/928/1705/92

Baseline characteristics

Age, Continuous
Age, Continuous(years)Sitagliptin 100 mgPlaceboTotal
Mean54.4 ± 8.854.8 ± 9.554.5 ± 9.0
Sex: Female, Male
Sex: Female, Male(Participants)Sitagliptin 100 mgPlaceboTotal
Female7437111
Male9655151
Race/Ethnicity
Race/Ethnicity(participants)Sitagliptin 100 mgPlaceboTotal
White8251133
Black7310
Hispanic131023
Asian582482
Other10414
HbA1c (Hemoglobin A1c)
HbA1c (Hemoglobin A1c)(Percent)Sitagliptin 100 mgPlaceboTotal
Mean8.8 ± 1.08.7 ± 1.08.8 ± 1.0
08

Study locations

No study locations are listed for this record.

09

References and documents

Publications

  • Dobs AS, Goldstein BJ, Aschner P, Horton ES, Umpierrez GE, Duran L, Hill JS, Chen Y, Golm GT, Langdon RB, Williams-Herman DE, Kaufman KD, Amatruda JM, Ferreira JC. Efficacy and safety of sitagliptin added to ongoing metformin and rosiglitazone combination therapy in a randomized placebo-controlled 54-week trial in patients with type 2 diabetes. J Diabetes. 2013 Mar;5(1):68-79. doi: 10.1111/j.1753-0407.2012.00223.x. PubMed 22742523 ↗

Individual participant data

Plan to share: Yes — http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf http://engagezone.msd.com/ds_documentation.php

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 12, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00350779
Lead sponsor
Merck Sharp & Dohme LLC
Responsible party
Sponsor
First posted
Jul 11, 2006
Start date
Jun 12, 2006
Primary completion
Sep 25, 2007
Completion
Jun 11, 2008
Results posted
Jul 3, 2009
Last update
May 12, 2017

Study contacts

Medical Monitor
study director · Merck Sharp & Dohme LLC

Oversight

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

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