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

Registration Number
NCT01189890
Lead Sponsor
Merck Sharp & Dohme LLC
Brief Summary

The primary objectives of this study are to determine if sitagliptin treatment is not inferior to that of glimepiride as measured by the change in baseline hemoglobin A1C (HbA1C) after 30 weeks of treatment, and if sitagliptin treatment results in a lower incidence of symptomatic hypoglycemia compared to that of glimepiride. The study will also evaluate if sitagliptin treatment, compared to glimepiride results in improvements in fasting plasma glucose (FPG) levels, and plasma lipid levels after 30 weeks of treatment. Participants will be randomized to either sitagliptin or glimepiride treatment after eligibility for study participation is determined during screening and washout study phases. Participants and study staff will not know to which treatment group they have been randomized (double-blind design). The duration of study participation will be up to 40 weeks (with 9 clinic visits). This will include a screening phase (Visit 1 to Visit 2) of 2 weeks maximum; a 6-week (Visits 2 to 3) oral antihyperglycemic agent (AHA) wash-out phase (for those who have been taking a AHA prior to the study); a placebo run-in phase (Visits 3 to 4), followed by up to 30 weeks of treatment with study medication.

Detailed Description

The dose of sitagliptin will be 100 mg once daily (QD) or 50 mg QD based on the participant's estimated glomerular filtration rate (eGFR). The starting dose of glimepiride (1 mg QD) may be up-titrated as needed to optimize glycemic control over the first 18 weeks to a maximum dose of 6 mg/day, after which the dose will not be increased for the rest of the study (down-titration to avoid or control hypoglycemia is allowed).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
480
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
SitagliptinPlacebo to GlimepirideSitagliptin phosphate 100 mg or 50 mg once daily (QD)
GlimepirideGlimepirideGlimepiride 1-6 mg QD
Sitagliptinsitagliptin phosphateSitagliptin phosphate 100 mg or 50 mg once daily (QD)
GlimepiridePlacebo to SitagliptinGlimepiride 1-6 mg QD
Primary Outcome Measures
NameTimeMethod
Least Squares (LS) Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 30Baseline and Week 30

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.

Number of Participants With an Adverse Event of Symptomatic Hypoglycemia Up to Week 30Up to Week 30

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.

Number of Participants Experiencing An Adverse Event (AE)Up to Week 30

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.

Number of Participants Discontinuing Study Treatment Due to An AEUp to Week 30

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.

Secondary Outcome Measures
NameTimeMethod
LS Mean Change From Baseline in Participant Body Weight at Week 30Baseline and Week 30

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.

LS Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 30Baseline and Week 30

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.

Percentage of Participants With HbA1c <7.0% at Week 30Week 30

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.

Percentage of Participants With HbA1c <6.5% at Week 30Week 30

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.

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