Type 2 Diabetes MellitusPhase 3NCT01760447

A Pooled Analysis of the Safety and Efficacy of MK-0431A and MK-0431A XR in Pediatric Participants With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Therapy (Alone or in Combination With Insulin) (MK-0431A-170/MK-0431A-289)

A Phase 3 study testing Sitagliptin plus metformin, Metformin and Sitagliptin plus metformin XR 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 10 to 17 years
Conditions the study is for: Type 2 Diabetes Mellitus
What is being tested?: Sitagliptin plus metformin, Metformin and Sitagliptin plus metformin XR
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 223 participants
Where: No sites listed yet
Study dates: 7 Dec 2011to 17 Sep 2019
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 10 to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

For MK-0431A-170 base study and MK-0431A-289:
Has type 2 diabetes mellitus (T2DM)
Is on metformin monotherapy (≥1500 mg/day) for ≥12 weeks with glycated hemoglobin (A1C) ≥6.5% and ≤10.0% OR is on stable doses of metformin (≥1500 mg/day) and insulin for ≥12 weeks with an A1C ≥7.0% and ≤10%. NOTE: Participants on a daily dose of metformin greater than or equal to 1000 mg/day, but less than 1500 mg/day may be eligible if there is documentation that higher doses are not tolerated.
Participant and a family member or adult closely involved in the daily activities will participate in the participant's treatment and study protocol (i.e., available for telephone calls, study visits and administration of study medication as needed).
Male, or female who is unlikely to conceive (non-sterilized, and is not sexually active or agrees to abstain from heterosexual activity or agrees to use an adequate method of contraception) during the study and for 14 days after the last dose of study drug
For MK-0431A-170 extension protocol:

Show all 9Show fewer

Has completed the P170 base study
Participant and a family member or adult closely involved in the daily activities will participate in the participant's treatment and study protocol (i.e., available for telephone calls, study visits and administration of study medication as needed).
Male, or female who is unlikely to conceive (non-sterilized, and is not sexually active or agrees to abstain from heterosexual activity or agrees to use an adequate method of contraception) during the study and for 14 days after the last dose of study drug

Who cannot join

For MK-0431A-170 base study and MK-0431A-289:
Has type 1 diabetes mellitus
Has monogenic diabetes or secondary diabetes
Has symptomatic hyperglycemia and/or moderate to large ketonuria and/or positive test for ketonemia, requiring immediate initiation of another antihyperglycemic agent
Has previously taken a dipeptidyl peptidase IV (DPP-4) inhibitor (such as sitagliptin, vildagliptin, alogliptin, saxagliptin, or linagliptin) or glucagon-like peptide-1 (GLP-1) receptor agonist (such as exenatide or liraglutide)
Is on or likely to require treatment for ≥2 consecutive weeks or repeated courses of corticosteroids (inhaled, nasal and topical corticosteroids are permitted)

Show all 24Show fewer

Has undergone a surgical procedure within 4 weeks of study participation or has planned major surgery during the study
History of congenital heart disease or cardiovascular disease other than hypertension
History of active liver disease (other than non-alcoholic steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease
Active neuropathy (such as nephrotic syndrome or glomerulonephritis)
Chronic myopathy, mitochondrial disorder or a progressive neurological or neuromuscular disorder
Human immunodeficiency virus (HIV)
Hematological disorder (such as aplastic anemia, thrombocytopenia, myeloproliferative or myelodysplastic syndromes)
Is currently being treated for hyperthyroidism or is on thyroid hormone therapy and has not been on a stable dose for at least 6 weeks
History of malignancy for ≤5 years prior to study participation, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer
History of idiopathic acute pancreatitis or chronic pancreatitis
History of recreational or illicit drug use, or of alcohol abuse or dependence (within the past year)
Has donated blood products or has had phlebotomy of >10% of estimated total blood volume within 8 weeks of study participation, or intends to donate blood products or receive blood products within the projected duration of the study
Is pregnant or breast-feeding, or is expecting to conceive or donate eggs during the study, including 14 days following the last dose of study drug
For MK-0431A-170 extension protocol:
Participant meets a study medication discontinuation criterion at the last visit of the MK-0431A-170 base study (Week 20)
Has taken the last dose of study medication for the MK-0431A-170 base study more than 14 days prior to Extension Visit 1
Has initiated another oral antihyperglycemic agent
Participant does not agree to refrain from participating in any other double-blind interventional study while participating in the P170 extension study

About this study

Official title: A Pooled Analysis of the Safety and Efficacy of MK-0431A and MK-0431A XR in Pediatric Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Therapy (Alone or in Combination With Insulin)

The purpose of this study is to assess the effect of the addition of sitagliptin (administered as MK-0431A or MK-0431A XR) relative to the addition of placebo on glycated hemoglobin (A1C), and the safety and tolerability of the addition of sitagliptin, in pediatric participants (ages 10-17 years) with type 2 diabetes mellitus with inadequate glycemic control on metformin therapy (alone or in combination with insulin). The primary hypothesis is that the addition of sitagliptin reduces glycated hemoglobin (A1C) more than the addition of placebo after 20 weeks of treatment.

Conditions: Type 2 Diabetes Mellitus
Being tested: Sitagliptin plus metformin, Placebo to metformin, Metformin, Placebo to sitagliptin plus metformin, Sitagliptin plus metformin XR
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 plus metforminDrug
Also called MK-0431A
Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal, to provide a total daily dose of 100 mg of sitagliptin and 1000 mg, 1700 mg or 2000 mg of metformin. Dosage of metformin was based on each participant's daily metformin dose prior to enrollment.
Placebo to metforminDrug
Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal. Each tablet contained placebo to metformin.
MetforminDrug
Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal, to provide a total daily dose of 1000 mg, 1700 mg or 2000 mg of metformin. Dosage was based on each participant's daily metformin dose prior to enrollment.
Placebo to sitagliptin plus metforminDrug
Also called Placebo to MK-0431A
Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal. Each tablet contained placebo to sitagliptin plus metformin.
Sitagliptin plus metformin XRDrug
Also called MK-0431A XR
Participants received 2 tablets daily, both taken together with a meal, to provide a total daily dose of 100 mg of sitagliptin and 1000 mg, 1500 mg or 2000 mg of metformin. Dosage of metformin XR was based on each participant's daily metformin dose prior to enrollment.
Placebo to metformin XRDrug
Participants received 2 tablets daily, both taken together with a meal. Each tablet contained placebo to metformin XR.
InsulinDrug
Participants who met protocol-specific glycemic rescue criteria received insulin as glycemic rescue therapy; participants on background insulin had their insulin dose increased for glycemic rescue. During Weeks 20-54, for participants who were not on background insulin or rescued with insulin during Weeks 0-20 in the "Sitagliptin/Metformin" and "Metformin" arms (protocol MK-0431A-170), and during Weeks 0-54 for participants not on background insulin in the "Sitagliptin/Metformin XR" and "Metformin XR" arms (protocol MK-0431A-289), the type of insulin for glycemic rescue was specified to be insulin glargine.
Placebo to sitagliptin plus metformin XRDrug
Also called Placebo to MK-0431A XR
Participants received 2 tablets daily, both taken together with a meal. Each tablet contained placebo to sitagliptin plus metformin XR.
Metformin XRDrug
Participants received 2 tablets daily, both taken together with a meal, to provide a total daily dose of 1000 mg, 1500 mg or 2000 mg of metformin XR. Dosage was based on each participant's daily metformin dose prior to enrollment.

Study groups in NCT01760447
Study group	Role	What they receive
Sitagliptin/Metformin	Experimental	Participants received one tablet of sitagliptin/metformin and one tablet of metformin-placebo, administered twice daily prior to the morning and evening meals, for up to 20 weeks in the base study alone, or for up to 54 weeks if the participant also entered the extension study. Participants in this arm were enrolled in protocol MK-0431A-170. Receives: Drug: Sitagliptin plus metformin; Drug: Placebo to metformin; Drug: Insulin
Metformin	Placebo comparator	Participants received one tablet of metformin and one tablet of placebo to sitagliptin/metformin, administered twice daily prior to the morning and evening meals, for up to 20 weeks in the base study alone, or for up to 54 weeks if the participant also entered the extension study. Participants in this arm were enrolled in protocol MK-0431A-170. Receives: Drug: Metformin; Drug: Placebo to sitagliptin plus metformin; Drug: Insulin
Sitagliptin/Metformin XR	Experimental	Participants received two tablets of sitagliptin/metformin XR and two tablets of metformin XR placebo, administered once daily with a meal, for up to 54 weeks. Participants in this arm were enrolled in protocol MK-0431A-289. Receives: Drug: Sitagliptin plus metformin XR; Drug: Placebo to metformin XR; Drug: Insulin
Metformin XR	Placebo comparator	Participants received two tablets of metformin XR and two tablets of placebo to sitagliptin/metformin XR, administered once daily with a meal, for up to 54 weeks. Participants in this arm were enrolled in protocol MK-0431A-289. Receives: Drug: Insulin; Drug: Placebo to sitagliptin plus metformin XR; Drug: Metformin XR

What is being measured

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

Change From Baseline in A1C at Week 20
Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Mean change from baseline at Week 20 was estimated from a longitudinal data analysis model.
Measured: Baseline and Week 20
Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-20
The number of participants experiencing ≥1 adverse event during Weeks 0-20 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Measured: Up to Week 20
Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-20
The number of participants who discontinued from study drug due to an adverse event during Weeks 0-20 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Measured: Up to Week 20
Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56
The number of participants experiencing ≥1 adverse event during Weeks 0-56 were reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Measured: Up to approximately Week 56
Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-54
The number of participants who discontinued from study drug due to an adverse event during Weeks 0-54 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Measured: Up to Week 54

Secondary outcomes (9)

Change From Baseline in A1C at Week 54
A1C is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Mean change from baseline at Week 54 was estimated from a longitudinal data analysis model.
Measured: Baseline and Week 54
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 20
Blood glucose was measured on a fasting basis. Mean change from baseline at Week 20 was estimated from a longitudinal data analysis model.
Measured: Baseline and Week 20
Change From Baseline in FPG at Week 54
Blood glucose was measured on a fasting basis. Mean change from baseline at Week 54 was estimated from a longitudinal data analysis model.
Measured: Baseline and Week 54
Percentage of Participants With A1C at Goal (<7.0%) at Week 20
Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Percentage of participants with A1C at goal (<7.0%) at Week 20 was presented.
Measured: Week 20
Percentage of Participants With A1C at Goal (<6.5%) at Week 20
Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Percentage of participants with A1C at goal (<6.5%) at Week 20 was presented.
Measured: Week 20
Percentage of Participants With A1C at Goal (<7.0%) at Week 54
Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Percentage of participants with A1C at goal (<7.0%) at Week 54 was presented.
Measured: Week 54
Percentage of Participants With A1C at Goal (<6.5%) at Week 54
Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Percentage of participants with A1C at goal (<6.5%) at Week 54 was presented.
Measured: Week 54
Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20
Percentage of participants who initiated glycemic rescue therapy prior to Week 20 was reported.
Measured: Up to Week 20
Percentage of Participants Initiating Insulin Glargine During Weeks 20-54
Percentage of participants who initiated insulin glargine therapy from Weeks 20 through 54 was reported.
Measured: Week 20 up to Week 54

Timeline

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

7 Dec 201117 Sep 2019

First posted4 Jan 2013 (estimated)
Study start7 Dec 2011
Primary completion17 Sep 2019
Study completion17 Sep 2019

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
Model description: Participants enrolled in protocol MK-0431A-170 were randomized between the arms "Sitagliptin/Metformin" and "Metformin." Participants enrolled in protocol MK-0431A-289 were randomized between the arms "Sitagliptin/Metformin XR" and "Metformin XR."
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 223 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01760447
Sponsor's protocol ID: 0431A-289
Other IDs: 2012-004035-23, 2011-002529-23, 2014-003583-20, MK-0431A-170, MK-0431A-289, CTRI/2012/09/003025, 2014
Status last verified: Sep 2022
First submitted: 2 Jan 2013
Last updated: 23 Sep 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

Jalaludin MY, Deeb A, Zeitler P, Garcia R, Newfield RS, Samoilova Y, Rosario CA, Shehadeh N, Saha CK, Zhang Y, Zilli M, Scherer LW, Lam RLH, Golm GT, Engel SS, Kaufman KD, Shankar RR. Efficacy and safety of the addition of sitagliptin to treatment of youth with type 2 diabetes and inadequate glycemic control on metformin without or with insulin. Pediatr Diabetes. 2022 Mar;23(2):183-193. doi: 10.1111/pedi.13282. Epub 2021 Dec 20.
PubMed 34779103

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 23 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Pooled Analysis of the Safety and Efficacy of MK-0431A and MK-0431A XR in Pediatric Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Therapy (Alone or in Combination With Insulin)
ClinicalTrials.gov ID: NCT01760447
Acronym / sponsor ID: 0431A-289
Conditions: Type 2 Diabetes Mellitus
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 223 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 7 Dec 2011 (actual)
Primary completion: 17 Sep 2019 (actual)
Study completion: 17 Sep 2019 (actual)
First posted: 4 Jan 2013 (estimated)
Results: Posted 5 Oct 2020

Clinical summary

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4
Model description: Participants enrolled in protocol MK-0431A-170 were randomized between the arms "Sitagliptin/Metformin" and "Metformin." Participants enrolled in protocol MK-0431A-289 were randomized between the arms "Sitagliptin/Metformin XR" and "Metformin XR."

Arm	Type	Receives
Sitagliptin/Metformin	Experimental	Drug: Sitagliptin plus metformin, Drug: Placebo to metformin, Drug: InsulinParticipants received one tablet of sitagliptin/metformin and one tablet of metformin-placebo, administered twice daily prior to the morning and evening meals, for up to 20 weeks in the base study alone, or for up to 54 weeks if the participant also entered the extension study. Participants in this arm were enrolled in protocol MK-0431A-170.
Metformin	Placebo comparator	Drug: Metformin, Drug: Placebo to sitagliptin plus metformin, Drug: InsulinParticipants received one tablet of metformin and one tablet of placebo to sitagliptin/metformin, administered twice daily prior to the morning and evening meals, for up to 20 weeks in the base study alone, or for up to 54 weeks if the participant also entered the extension study. Participants in this arm were enrolled in protocol MK-0431A-170.
Sitagliptin/Metformin XR	Experimental	Drug: Sitagliptin plus metformin XR, Drug: Placebo to metformin XR, Drug: InsulinParticipants received two tablets of sitagliptin/metformin XR and two tablets of metformin XR placebo, administered once daily with a meal, for up to 54 weeks. Participants in this arm were enrolled in protocol MK-0431A-289.
Metformin XR	Placebo comparator	Drug: Insulin, Drug: Placebo to sitagliptin plus metformin XR, Drug: Metformin XRParticipants received two tablets of metformin XR and two tablets of placebo to sitagliptin/metformin XR, administered once daily with a meal, for up to 54 weeks. Participants in this arm were enrolled in protocol MK-0431A-289.

Who may qualify

Ages: 10 to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (9 listed)

For MK-0431A-170 base study and MK-0431A-289:
For MK-0431A-170 extension protocol:

Key exclusion criteria (24 listed)

For MK-0431A-170 base study and MK-0431A-289:
For MK-0431A-170 extension protocol:

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 plus metforminAlso: MK-0431AParticipants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal, to provide a total daily dose of 100 mg of sitagliptin and 1000 mg, 1700 mg or 2000 mg of metformin. Dosage of metformin was based on each participant's daily metformin dose prior to enrollment.	Drug	Sitagliptin/Metformin
Placebo to metforminParticipants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal. Each tablet contained placebo to metformin.	Drug	Sitagliptin/Metformin
MetforminParticipants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal, to provide a total daily dose of 1000 mg, 1700 mg or 2000 mg of metformin. Dosage was based on each participant's daily metformin dose prior to enrollment.	Drug	Metformin
Placebo to sitagliptin plus metforminAlso: Placebo to MK-0431AParticipants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal. Each tablet contained placebo to sitagliptin plus metformin.	Drug	Metformin
Sitagliptin plus metformin XRAlso: MK-0431A XRParticipants received 2 tablets daily, both taken together with a meal, to provide a total daily dose of 100 mg of sitagliptin and 1000 mg, 1500 mg or 2000 mg of metformin. Dosage of metformin XR was based on each participant's daily metformin dose prior to enrollment.	Drug	Sitagliptin/Metformin XR
Placebo to metformin XRParticipants received 2 tablets daily, both taken together with a meal. Each tablet contained placebo to metformin XR.	Drug	Sitagliptin/Metformin XR
InsulinParticipants who met protocol-specific glycemic rescue criteria received insulin as glycemic rescue therapy; participants on background insulin had their insulin dose increased for glycemic rescue. During Weeks 20-54, for participants who were not on background insulin or rescued with insulin during Weeks 0-20 in the "Sitagliptin/Metformin" and "Metformin" arms (protocol MK-0431A-170), and during Weeks 0-54 for participants not on background insulin in the "Sitagliptin/Metformin XR" and "Metformin XR" arms (protocol MK-0431A-289), the type of insulin for glycemic rescue was specified to be insulin glargine.	Drug	Metformin, Metformin XR, Sitagliptin/Metformin, Sitagliptin/Metformin XR
Placebo to sitagliptin plus metformin XRAlso: Placebo to MK-0431A XRParticipants received 2 tablets daily, both taken together with a meal. Each tablet contained placebo to sitagliptin plus metformin XR.	Drug	Metformin XR
Metformin XRParticipants received 2 tablets daily, both taken together with a meal, to provide a total daily dose of 1000 mg, 1500 mg or 2000 mg of metformin XR. Dosage was based on each participant's daily metformin dose prior to enrollment.	Drug	Metformin XR

Primary outcome

Change From Baseline in A1C at Week 20
Time frame: Baseline and Week 20
Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Mean change from baseline at Week 20 was estimated from a longitudinal data analysis model.
Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-20
Time frame: Up to Week 20
The number of participants experiencing ≥1 adverse event during Weeks 0-20 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-20
Time frame: Up to Week 20
The number of participants who discontinued from study drug due to an adverse event during Weeks 0-20 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56
Time frame: Up to approximately Week 56
The number of participants experiencing ≥1 adverse event during Weeks 0-56 were reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-54
Time frame: Up to Week 54
The number of participants who discontinued from study drug due to an adverse event during Weeks 0-54 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

9 secondary outcomes

Change From Baseline in A1C at Week 54
Time frame: Baseline and Week 54
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 20
Time frame: Baseline and Week 20
Change From Baseline in FPG at Week 54
Time frame: Baseline and Week 54
Percentage of Participants With A1C at Goal (<7.0%) at Week 20
Time frame: Week 20
Percentage of Participants With A1C at Goal (<6.5%) at Week 20
Time frame: Week 20
Percentage of Participants With A1C at Goal (<7.0%) at Week 54
Time frame: Week 54
Percentage of Participants With A1C at Goal (<6.5%) at Week 54
Time frame: Week 54
Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20
Time frame: Up to Week 20
Percentage of Participants Initiating Insulin Glargine During Weeks 20-54
Time frame: Week 20 up to Week 54

Results and safety

Results posted to the registry on 5 Oct 2020, 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/Metformin	62	59
Metformin	62	62
Sitagliptin/Metformin XR	47	42
Metformin XR	51	47

Primary outcome: Change From Baseline in A1C at Week 20

Time frame: Baseline and Week 20. Least squares mean (95% Confidence Interval). Unit: Percentage of glycated hemoglobin

Measure	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled n = 107	Metformin and Metformin XR Pooled n = 113
Value	-0.58 (-0.94 to -0.22)	-0.09 (-0.43 to 0.26)

Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled vs Metformin and Metformin XR Pooled: Least Squares Mean Difference: -0.49 (95% CI -0.90 to -0.09), p = 0.018, Mixed Models Analysis

Population analysed: The analysis population includes all randomized participants who received ≥1 dose of study medication and who had at least 1 measurement of A1C. As defined in the protocols, these analyses were conducted in participants pooled from protocols MK-0431A-170 and MK-0431A-289, pooled according to receipt of experimental drug or placebo comparator.

Primary outcome: Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-20

Time frame: Up to Week 20. Count of participants. Unit: Participants

Measure	Sitagliptin/Metformin n = 62	Metformin n = 62	Sitagliptin/Metformin XR n = 45	Metformin XR n = 51	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled n = 107	Metformin and Metformin XR Pooled n = 113
Value	42	46	29	30	71	76

Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled vs Metformin and Metformin XR Pooled: Difference in Percentage: -1.3 (95% CI -13.9 to 11.3)

Population analysed: The analysis population includes all randomized participants who received ≥1 dose of study medication.

Primary outcome: Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-20

Time frame: Up to Week 20. Count of participants. Unit: Participants

Measure	Sitagliptin/Metformin n = 62	Metformin n = 62	Sitagliptin/Metformin XR n = 45	Metformin XR n = 51	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled n = 107	Metformin and Metformin XR Pooled n = 113
Value	1	2	2	2	3	4

Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled vs Metformin and Metformin XR Pooled: Difference in Percentage: -0.5 (95% CI -6.2 to 5.0)

Population analysed: The analysis population includes all randomized participants who received ≥1 dose of study medication.

Primary outcome: Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56

Time frame: Up to approximately Week 56. Count of participants. Unit: Participants

Measure	Sitagliptin/Metformin n = 28	Metformin n = 30	Sitagliptin/Metformin XR n = 42	Metformin XR n = 47	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled n = 70	Metformin and Metformin XR Pooled n = 77
Value	26	27	36	39	62	66

Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled vs Metformin and Metformin XR Pooled: Difference in Percentage: 2.9 (95% CI -8.9 to 14.4)

Population analysed: The analysis population includes all randomized participants who received ≥1 dose of study medication and continued in the study beyond Week 20.

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 56 weeks for non-serious adverse events. Up to approximately 76 weeks for serious adverse events. Up to approximately 78 weeks for all-cause mortality.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Sitagliptin/Metformin	4 of 62 (6.5%)	34 of 62 (54.8%)	1 of 62
Metformin	3 of 62 (4.8%)	40 of 62 (64.5%)	0 of 62
Sitagliptin/Metformin XR	3 of 45 (6.7%)	30 of 45 (66.7%)	0 of 47
Metformin XR	3 of 51 (5.9%)	36 of 51 (70.6%)	0 of 51
Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	7 of 107 (6.5%)	64 of 107 (59.8%)	1 of 109
Metformin and Metformin XR Pooled	6 of 113 (5.3%)	76 of 113 (67.3%)	0 of 113

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 34779103Jalaludin MY, Deeb A, Zeitler P, Garcia R, Newfield RS, Samoilova Y, Rosario CA, Shehadeh N, Saha CK, Zhang Y, Zilli M, Scherer LW, Lam RLH, Golm GT, Engel SS, Kaufman KD, Shankar RR. Efficacy and safety of the addition of sitagliptin to treatment of youth with type 2 diabetes and inadequate glycemic control on metformin without or with insulin. Pediatr Diabetes. 2022 Mar;23(2):183-193. doi: 10.1111/pedi.13282. Epub 2021 Dec 20.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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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.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Sitagliptin plus metformin, Metformin and Sitagliptin plus metformin XR 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 9 inclusion and 24 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 23 Sep 2022. 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. Some participants in this study may receive a placebo. 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 5 Oct 2020). 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?

Change From Baseline in A1C at Week 20 (time frame: Baseline and Week 20). The study lists 5 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 NCT01760447, 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 23 Sep 2022.