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Safety and Efficacy of Sitagliptin Compared With Glimepiride in Elderly Participants With Type 2 Diabetes Mellitus (MK-0431-251)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01189890
First received: August 25, 2010
Last updated: November 10, 2014
Last verified: November 2014
Results First Received: May 8, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Type 2 Diabetes Mellitus
Interventions: Drug: sitagliptin phosphate
Drug: Glimepiride
Drug: Placebo to Sitagliptin
Drug: Placebo to Glimepiride

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Sitagliptin Sitagliptin phosphate 100 mg once daily (QD) or 50 mg QD
Glimepiride Glimepiride 1-6 mg QD

Participant Flow:   Overall Study
    Sitagliptin     Glimepiride  
STARTED     241     239 [1]
COMPLETED     204     200  
NOT COMPLETED     37     39  
Adverse Event                 3                 4  
Lack of Efficacy                 7                 2  
Lost to Follow-up                 1                 7  
Protocol Violation                 1                 5  
Withdrawal by Subject                 15                 11  
Non Compliance                 0                 1  
Physician Decision                 5                 4  
Hyperglycemia Discontinuation Criteria                 5                 5  
[1] 3 randomized glimepiride participants did not receive study drug.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
Sitagliptin Sitagliptin phosphate 100 mg once daily (QD) or 50 mg QD
Glimepiride Glimepiride 1-6 mg QD
Total Total of all reporting groups

Baseline Measures
    Sitagliptin     Glimepiride     Total  
Number of Participants  
[units: participants]
  241     239     480  
Age  
[units: years]
Mean ± Standard Deviation
  70.7  ± 4.8     70.8  ± 4.9     70.7  ± 4.8  
Gender  
[units: participants]
     
Female     130     148     278  
Male     111     91     202  
Hemoglobin A1c (HbA1c) [1]
[units: Percentage of HbA1c]
Mean ± Standard Deviation
  7.78  ± 0.70     7.78  ± 0.67     7.78  ± 0.69  
Fasting Plasma Glucose (FPG) [2]
[units: mg/dL]
Mean ± Standard Deviation
  168.4  ± 31.2     169.7  ± 35.5     169.0  ± 33.3  
Body Weight [3]
[units: kg]
Mean ± Standard Deviation
  76.9  ± 15.1     75.4  ± 16.4     76.0  ± 15.6  
[1] The population included all randomized participants who had a baseline HbA1c, did not take prohibited concomitant medications, had compliance >85%, and did not receive any incorrect study medication. Sitagliptin (n=197) and glimepiride (n=191).
[2] The population included all randomized participants who had a baseline FPG, did not take prohibited concomitant medications, had compliance >85%, and did not receive any incorrect study medication. Sitagliptin (n=194) and glimepiride (n=191).
[3] All randomized participants who received at least one dose of study treatment and had a body weight measurement at baseline. Sitagliptin (n=205) and glimepiride (n=203).



  Outcome Measures
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1.  Primary:   Least Squares (LS) Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 30   [ Time Frame: Baseline and Week 30 ]

Measure Type Primary
Measure Title Least Squares (LS) Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 30
Measure Description Participant whole blood samples were collected at baseline and Week 30 to determine the LS mean HbA1c change from baseline. HbA1c is a measure of the percentage of glycated hemoglobin in the blood and provides an indication of participant blood glucose control in the 2 to 3 months prior to the evaluation.
Time Frame Baseline and Week 30  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The population included all randomized participants who had a baseline HbA1c, had a HbA1c at Week 30, did not take prohibited concomitant medications, had compliance >85%, and did not receive any incorrect study medication.

Reporting Groups
  Description
Sitagliptin Sitagliptin phosphate 100 mg once daily (QD) or 50 mg QD
Glimepiride Glimepiride 1-6 mg QD

Measured Values
    Sitagliptin     Glimepiride  
Number of Participants Analyzed  
[units: participants]
  197     191  
Least Squares (LS) Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 30  
[units: Percentage of HbA1c]
Least Squares Mean ( 95% Confidence Interval )
  -0.32  
  ( -0.51 to -0.14 )  
  -0.51  
  ( -0.69 to -0.33 )  


Statistical Analysis 1 for Least Squares (LS) Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 30
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] ANCOVA
Difference in LS Means [4] 0.19
95% Confidence Interval ( 0.03 to 0.34 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  The predefined non-inferiority margin was 0.4%.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Controlled for treatment, estimated glomerular filtration rate (eGFR) stratum, age stratum, and baseline HbA1C.
[4] Other relevant estimation information:
  No text entered.



2.  Primary:   Number of Participants With an Adverse Event of Symptomatic Hypoglycemia Up to Week 30   [ Time Frame: Up to Week 30 ]

Measure Type Primary
Measure Title Number of Participants With an Adverse Event of Symptomatic Hypoglycemia Up to Week 30
Measure Description Symptomatic hypoglycemia was defined as an episode with clinical symptoms attributed to hypoglycemia, without regard to glucose level. Participants were instructed to complete the Hypoglycemia Assessment Log (HAL) for any symptomatic episodes he or she believed represent hypoglycemia. If a fingerstick glucose was obtained before or shortly (i.e., within a few minutes) after treating, the value was recorded in the HAL. In addition, participants were instructed to record in the HAL any fingerstick glucose values ≤70 mg/dL (≤3.9 mmol/L) regardless of the presence of clinical symptoms.
Time Frame Up to Week 30  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who received at least one dose of study treatment.

Reporting Groups
  Description
Sitagliptin Sitagliptin phosphate 100 mg once daily (QD) or 50 mg QD
Glimepiride Glimepiride 1-6 mg QD

Measured Values
    Sitagliptin     Glimepiride  
Number of Participants Analyzed  
[units: participants]
  241     236  
Number of Participants With an Adverse Event of Symptomatic Hypoglycemia Up to Week 30  
[units: Participants]
  2     11  


Statistical Analysis 1 for Number of Participants With an Adverse Event of Symptomatic Hypoglycemia Up to Week 30
Groups [1] All groups
Method [2] Miettinen & Nurminen
P Value [3] 0.009
Difference in Percent Incidence [4] -3.9
95% Confidence Interval ( -7.5 to -1.2 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Stratified by estimated glomerular filtration rate (eGFR) stratum and age stratum.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



3.  Primary:   Number of Participants Experiencing An Adverse Event (AE)   [ Time Frame: Up to Week 30 ]

Measure Type Primary
Measure Title Number of Participants Experiencing An Adverse Event (AE)
Measure Description

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the

study treatment, whether or not considered related to the use of the treatment administered.

Time Frame Up to Week 30  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who received at least one dose of study treatment.

Reporting Groups
  Description
Sitagliptin Sitagliptin phosphate 100 mg once daily (QD) or 50 mg QD
Glimepiride Glimepiride 1-6 mg QD

Measured Values
    Sitagliptin     Glimepiride  
Number of Participants Analyzed  
[units: participants]
  241     236  
Number of Participants Experiencing An Adverse Event (AE)  
[units: Participants]
  118     115  

No statistical analysis provided for Number of Participants Experiencing An Adverse Event (AE)



4.  Primary:   Number of Participants Discontinuing Study Treatment Due to An AE   [ Time Frame: Up to Week 30 ]

Measure Type Primary
Measure Title Number of Participants Discontinuing Study Treatment Due to An AE
Measure Description

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the

study treatment, whether or not considered related to the use of the treatment administered.

Time Frame Up to Week 30  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who received at least one dose of study treatment.

Reporting Groups
  Description
Sitagliptin Sitagliptin phosphate 100 mg once daily (QD) or 50 mg QD
Glimepiride Glimepiride 1-6 mg QD

Measured Values
    Sitagliptin     Glimepiride  
Number of Participants Analyzed  
[units: participants]
  241     236  
Number of Participants Discontinuing Study Treatment Due to An AE  
[units: Participants]
  3     4  

No statistical analysis provided for Number of Participants Discontinuing Study Treatment Due to An AE



5.  Secondary:   LS Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 30   [ Time Frame: Baseline and Week 30 ]

Measure Type Secondary
Measure Title LS Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 30
Measure Description Plasma samples were collected from participants after an overnight fast at baseline and Week 30 to determine the mean change from baseline in participant FPG.
Time Frame Baseline and Week 30  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The population included all randomized participants who had a FPG value at baseline and Week 30, did not take prohibited concomitant medications, had compliance >85%, and did not receive any incorrect study medication.

Reporting Groups
  Description
Sitagliptin Sitagliptin phosphate 100 mg once daily (QD) or 50 mg QD
Glimepiride Glimepiride 1-6 mg QD

Measured Values
    Sitagliptin     Glimepiride  
Number of Participants Analyzed  
[units: participants]
  194     191  
LS Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 30  
[units: mg/dL]
Least Squares Mean ( 95% Confidence Interval )
  -14.5  
  ( -21.6 to -7.4 )  
  -21.2  
  ( -28.3 to -14.0 )  


Statistical Analysis 1 for LS Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 30
Groups [1] All groups
Method [2] ANCOVA
Difference in LS Means [3] 6.7
95% Confidence Interval ( 0.7 to 12.7 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Controlled for treatment, eGFR stratum, age stratum, and baseline FPG.
[3] Other relevant estimation information:
  No text entered.



6.  Secondary:   Percentage of Participants With HbA1c <7.0% at Week 30   [ Time Frame: Week 30 ]

Measure Type Secondary
Measure Title Percentage of Participants With HbA1c <7.0% at Week 30
Measure Description Participant whole blood samples were collected at Week 30 to determine the number of participants achieving HbA1c <7.0% at Week 30. HbA1c is a measure of the percentage of glycated hemoglobin in the blood and provides an indication of participant blood glucose control in the 2 to 3 months prior to the evaluation.
Time Frame Week 30  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The population included all randomized participants who had HbA1c at baseline and Week 30, did not take prohibited concomitant medications, had compliance >85%, and did not receive any incorrect study medication.

Reporting Groups
  Description
Sitagliptin Sitagliptin phosphate 100 mg once daily (QD) or 50 mg QD
Glimepiride Glimepiride 1-6 mg QD

Measured Values
    Sitagliptin     Glimepiride  
Number of Participants Analyzed  
[units: participants]
  197     191  
Percentage of Participants With HbA1c <7.0% at Week 30  
[units: Percentage of Participants]
  33.5     46.6  


Statistical Analysis 1 for Percentage of Participants With HbA1c <7.0% at Week 30
Groups [1] All groups
Method [2] Miettinen & Nurminen
Relative Risk [3] 0.7
95% Confidence Interval ( 0.6 to 0.9 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Stratified by eGFR stratum and age stratum.
[3] Other relevant estimation information:
  No text entered.



7.  Secondary:   Percentage of Participants With HbA1c <6.5% at Week 30   [ Time Frame: Week 30 ]

Measure Type Secondary
Measure Title Percentage of Participants With HbA1c <6.5% at Week 30
Measure Description Participant whole blood samples were collected at Week 30 to determine the number of participants achieving HbA1c <6.5% at Week 30. Hemoglobin A1c is a measure of the percentage of glycated hemoglobin in the blood and provides an indication of participant blood glucose control in the 2 to 3 months prior to the evaluation.
Time Frame Week 30  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The population included all randomized participants who had HbA1c at baseline and Week 30, did not take prohibited concomitant medications, had compliance >85%, and did not receive any incorrect study medication.

Reporting Groups
  Description
Sitagliptin Sitagliptin phosphate 100 mg once daily (QD) or 50 mg QD
Glimepiride Glimepiride 1-6 mg QD

Measured Values
    Sitagliptin     Glimepiride  
Number of Participants Analyzed  
[units: participants]
  197     191  
Percentage of Participants With HbA1c <6.5% at Week 30  
[units: Percentage of Participants]
  9.1     20.9  


Statistical Analysis 1 for Percentage of Participants With HbA1c <6.5% at Week 30
Groups [1] All groups
Method [2] Miettinen & Nurminen
Relative Risk [3] 0.4
95% Confidence Interval ( 0.3 to 0.7 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Stratified by eGFR stratum and age stratum.
[3] Other relevant estimation information:
  No text entered.



8.  Secondary:   LS Mean Change From Baseline in Participant Body Weight at Week 30   [ Time Frame: Baseline and Week 30 ]

Measure Type Secondary
Measure Title LS Mean Change From Baseline in Participant Body Weight at Week 30
Measure Description Participants were only permitted to wear a drape gown and undergarments (no street clothes, no shoes or socks) for this evaluation. Body weight was measured after voiding (to the nearest 0.1 kg) and measurements were collected until 2 consecutive measurements did not differ by more than 0.2 kg from each other. Body weight measurements were evaluated using a standardized, calibrated digital scale and was reported in kilograms (kg) at baseline and Week 30.
Time Frame Baseline and Week 30  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who received at least one dose of study treatment and had body weight measurements at baseline and at Week 30.

Reporting Groups
  Description
Sitagliptin Sitagliptin phosphate 100 mg once daily (QD) or 50 mg QD
Glimepiride Glimepiride 1-6 mg QD

Measured Values
    Sitagliptin     Glimepiride  
Number of Participants Analyzed  
[units: participants]
  205     203  
LS Mean Change From Baseline in Participant Body Weight at Week 30  
[units: kg]
Least Squares Mean ( 95% Confidence Interval )
  0.4  
  ( -0.2 to 1.0 )  
  1.1  
  ( 0.5 to 1.7 )  


Statistical Analysis 1 for LS Mean Change From Baseline in Participant Body Weight at Week 30
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.011
Difference in LS Means [4] -0.7
95% Confidence Interval ( -1.3 to -0.2 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Controlled for treatment, eGFR stratum, age stratum, and baseline body weight.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information