Type 2 Diabetes MellitusPhase 3NCT01189890

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

A Phase 3 study testing sitagliptin phosphate and Glimepiride in people with Type 2 Diabetes Mellitus, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 65 to 85 years
Conditions the study is for: Type 2 Diabetes Mellitus
What is being tested?: sitagliptin phosphate and Glimepiride
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 480 participants
Where: No sites listed yet
Study dates: 16 Aug 2010to 31 Oct 2012
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 65 to 85 years
All sexes
No healthy volunteers
Older adult

Who may be able to join

Diagnosis of type 2 diabetes mellitus

Who cannot join

History of type 1 diabetes mellitus
Has undergone a surgical procedure within the prior 4 weeks.
Current participation in, or has participated, in another study with an investigational device or compound, with the prior 12 weeks, and/or is not willing to refrain from participating in any other study while participating in this study
Hypersensitivity or contraindication to any sulfonylurea (e.g., glimepiride) medication
Has been on an investigational or approved dipeptidyl peptidase-4 (DPP-4) inhibitor agent (e.g., sitagliptin, saxagliptin)
Presence of human immunodeficiency virus (HIV)

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Current participation in a weight loss program or is receiving weight loss medication
History of blood disorder, certain cancers, heart, liver or kidney disease
Current or past use of recreational or illicit drugs, or a history of drug abuse or dependence, or increased alcohol consumption

About this study

Official title: A Phase III, Multicenter, Double-Blind, Randomized, Active-Controlled Study to Evaluate the Safety and Efficacy of Sitagliptin Compared With Glimepiride in Elderly Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control

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.

Read the 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).

Conditions: Type 2 Diabetes Mellitus
Being tested: sitagliptin phosphate, Glimepiride, Placebo to Sitagliptin, Placebo to Glimepiride
Keywords: Type 2 Diabetes Mellitus, Hemoglobin A1C, glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), dipeptidyl peptidase 4 inhibitor (DPP-4)
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

sitagliptin phosphateDrug
Also called Januvia
Sitagliptin tablets, orally, at a dose of 100 mg or 50 mg QD for 30 weeks. The dose level to be administered will depend on the participant's estimated glomerular filtration rate (eGFR), calculated at Visit 3 and may be adjusted as medically indicated during the study.
GlimepirideDrug
Also called Amaryl
Glimepiride tablets, orally, starting at a dose of 1 mg QD, which may be gradually increased, as needed, to maximum dose of 6 mg QD for 30 weeks. The dose may also be decreased as medically indicated during the study.
Placebo to SitagliptinDrug
Matching placebo tablets to sitagliptin to allow for blinding.
Placebo to GlimepirideDrug
Matching placebo tablets to glimepiride to allow for blinding.

Study groups in NCT01189890
Study group	Role	What they receive
Sitagliptin	Experimental	Sitagliptin phosphate 100 mg or 50 mg once daily (QD) Receives: Drug: sitagliptin phosphate; Drug: Placebo to Glimepiride
Glimepiride	Active comparator	Glimepiride 1-6 mg QD Receives: Drug: Glimepiride; Drug: Placebo to Sitagliptin

What is being measured

The primary outcome is the main question the study is designed to answer.

Least Squares (LS) Mean Change From Baseline in Hemoglobin A1c (HbA1c) at 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.
Measured: Baseline and Week 30
Number of Participants With an Adverse Event of Symptomatic Hypoglycemia Up 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.
Measured: Up to Week 30
Number of Participants Experiencing An Adverse Event (AE)
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.
Measured: Up to Week 30
Number of Participants Discontinuing Study Treatment Due to An AE
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.
Measured: Up to Week 30

Secondary outcomes (4)

LS Mean Change From Baseline in Fasting Plasma Glucose (FPG) at 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.
Measured: Baseline and Week 30
Percentage of Participants With HbA1c <7.0% at Week 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.
Measured: Week 30
Percentage of Participants With HbA1c <6.5% at Week 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.
Measured: Week 30
LS Mean Change From Baseline in Participant Body Weight at 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.
Measured: Baseline and Week 30

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Aug 201031 Oct 2012

First posted27 Aug 2010 (estimated)
Study start16 Aug 2010
Primary completion31 Oct 2012
Study completion31 Oct 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 480 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01189890
Sponsor's protocol ID: 0431-251
Status last verified: May 2017
First submitted: 25 Aug 2010
Last updated: 5 Jun 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: 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

Publications

Hartley P, Shentu Y, Betz-Schiff P, Golm GT, Sisk CM, Engel SS, Shankar RR. Efficacy and Tolerability of Sitagliptin Compared with Glimepiride in Elderly Patients with Type 2 Diabetes Mellitus and Inadequate Glycemic Control: A Randomized, Double-Blind, Non-Inferiority Trial. Drugs Aging. 2015 Jun;32(6):469-76. doi: 10.1007/s40266-015-0271-z.
PubMed 26041585

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 5 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase III, Multicenter, Double-Blind, Randomized, Active-Controlled Study to Evaluate the Safety and Efficacy of Sitagliptin Compared With Glimepiride in Elderly Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control
ClinicalTrials.gov ID: NCT01189890
Acronym / sponsor ID: 0431-251
Conditions: Type 2 Diabetes Mellitus
Keywords: Type 2 Diabetes Mellitus, Hemoglobin A1C, glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), dipeptidyl peptidase 4 inhibitor (DPP-4)
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 480 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 16 Aug 2010 (actual)
Primary completion: 31 Oct 2012 (actual)
Study completion: 31 Oct 2012 (actual)
First posted: 27 Aug 2010 (estimated)
Results: Posted 27 Jun 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Sitagliptin	Experimental	Drug: sitagliptin phosphate, Drug: Placebo to GlimepirideSitagliptin phosphate 100 mg or 50 mg once daily (QD)
Glimepiride	Active comparator	Drug: Glimepiride, Drug: Placebo to SitagliptinGlimepiride 1-6 mg QD

Who may qualify

Ages: 65 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Older adult

Key inclusion criteria (1 listed)

Diagnosis of type 2 diabetes mellitus

Key exclusion criteria (9 listed)

History of type 1 diabetes mellitus
Has undergone a surgical procedure within the prior 4 weeks.
Current participation in, or has participated, in another study with an investigational device or compound, with the prior 12 weeks, and/or is not willing to refrain from participating in any other study while participating in this study
Hypersensitivity or contraindication to any sulfonylurea (e.g., glimepiride) medication
Has been on an investigational or approved dipeptidyl peptidase-4 (DPP-4) inhibitor agent (e.g., sitagliptin, saxagliptin)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
sitagliptin phosphateAlso: JanuviaSitagliptin tablets, orally, at a dose of 100 mg or 50 mg QD for 30 weeks. The dose level to be administered will depend on the participant's estimated glomerular filtration rate (eGFR), calculated at Visit 3 and may be adjusted as medically indicated during the study.	Drug	Sitagliptin
GlimepirideAlso: AmarylGlimepiride tablets, orally, starting at a dose of 1 mg QD, which may be gradually increased, as needed, to maximum dose of 6 mg QD for 30 weeks. The dose may also be decreased as medically indicated during the study.	Drug	Glimepiride
Placebo to SitagliptinMatching placebo tablets to sitagliptin to allow for blinding.	Drug	Glimepiride
Placebo to GlimepirideMatching placebo tablets to glimepiride to allow for blinding.	Drug	Sitagliptin

Primary outcome

Least Squares (LS) Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 30
Time frame: Baseline 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 30
Time frame: Up 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)
Time frame: 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 AE
Time frame: 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.

4 secondary outcomes

LS Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 30
Time frame: Baseline and Week 30
Percentage of Participants With HbA1c <7.0% at Week 30
Time frame: Week 30
Percentage of Participants With HbA1c <6.5% at Week 30
Time frame: Week 30
LS Mean Change From Baseline in Participant Body Weight at Week 30
Time frame: Baseline and Week 30

Results and safety

Results posted to the registry on 27 Jun 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sitagliptin	241	204
Glimepiride	239	200

Primary outcome: Least Squares (LS) Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 30

Time frame: Baseline and Week 30. Least squares mean (95% Confidence Interval). Unit: Percentage of HbA1c

Measure	Sitagliptin n = 197	Glimepiride n = 191
Value	-0.32 (0.78)	-0.51 (0.89)

Sitagliptin vs Glimepiride: Difference in LS Means: 0.19 (95% CI 0.03 to 0.34), ANCOVA

Population analysed: 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.

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

Time frame: Up to Week 30. Number. Unit: Participants

Measure	Sitagliptin n = 241	Glimepiride n = 236
Value	2	11

Sitagliptin vs Glimepiride: Difference in Percent Incidence: -3.9 (95% CI -7.5 to -1.2), p = 0.009, Miettinen & Nurminen

Population analysed: All randomized participants who received at least one dose of study treatment.

Primary outcome: Number of Participants Experiencing An Adverse Event (AE)

Time frame: Up to Week 30. Number. Unit: Participants

Measure	Sitagliptin n = 241	Glimepiride n = 236
Value	118	115

Population analysed: All randomized participants who received at least one dose of study treatment.

Primary outcome: Number of Participants Discontinuing Study Treatment Due to An AE

Time frame: Up to Week 30. Number. Unit: Participants

Measure	Sitagliptin n = 241	Glimepiride n = 236
Value	3	4

Population analysed: All randomized participants who received at least one dose of study treatment.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to Week 32.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Sitagliptin	7 of 241 (2.9%)	34 of 241 (14.1%)	Not reported
Glimepiride	6 of 236 (2.5%)	40 of 236 (16.9%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 26041585Hartley P, Shentu Y, Betz-Schiff P, Golm GT, Sisk CM, Engel SS, Shankar RR. Efficacy and Tolerability of Sitagliptin Compared with Glimepiride in Elderly Patients with Type 2 Diabetes Mellitus and Inadequate Glycemic Control: A Randomized, Double-Blind, Non-Inferiority Trial. Drugs Aging. 2015 Jun;32(6):469-76. doi: 10.1007/s40266-015-0271-z.
Individual participant dataSharing planned: 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

Related trials for Type 2 Diabetes Mellitus

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing sitagliptin phosphate and Glimepiride in people with Type 2 Diabetes Mellitus, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jun 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Least Squares (LS) Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 30 (time frame: Baseline and Week 30). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01189890, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2017.