Comparison of Two Treatment Regimens (Sitagliptin Versus Liraglutide) on Participants Who Failed to Achieve Good Glucose Control on Metformin Alone (MK-0431-403)

NCT ID: NCT01296412

Last Updated: 2017-06-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 653 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-11
• Study Completion Date: 2012-02-29

Brief Summary

This study is being done to compare the effectiveness and safety of two treatment paradigms (oral sitagliptin with or without glimepiride versus liraglutide with or without increased dosing) for the treatment of participants with Type 2 Diabetes that is not adequately controlled with metformin alone. The primary hypothesis postulated that the mean change from baseline in hemoglobin A1c (A1C) in participants treated with a sitagliptin-based treatment is non-inferior to that of participants treated with a liraglutide-based

treatment.

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sitagliptin +/- glimepiride

Sitagliptin 100 mg tablet orally once daily for 26 weeks. Participants continued their stable dose of metformin \>=1500 mg orally daily. Participants may have received glimepiride orally for glycemic control.

Group Type: EXPERIMENTAL

sitagliptin

Intervention Type: DRUG

100 mg tablet, orally, once daily.

glimepiride

Intervention Type: DRUG

starting dose of 1 mg tablet (up-titrated as needed), once daily, as needed, after Week 12.

metformin

Intervention Type: DRUG

metformin tablets at a dose of ≥1500 mg per day

Liraglutide

Liraglutide subcutaneous injection once daily for 26 weeks (starting dose 0.6 mg daily up-titrated to 1.2 mg daily on Day 8). Participants continued their stable dose of metformin \>=1500 mg orally daily. Participants may have had their liraglutide dose uptitrated to 1.8 mg daily for glycemic control.

Group Type: ACTIVE_COMPARATOR

liraglutide

Intervention Type: DRUG

0.6 mg by subcutaneous (pen) injection, once daily, on Days 1-7; up-titrated on Day 8 to 1.2 mg daily. At Week 12, dose may be increased to 1.8 mg once daily for participants who did not meet protocol-specified glycemic goals.

metformin

Intervention Type: DRUG

metformin tablets at a dose of ≥1500 mg per day

Interventions

sitagliptin

100 mg tablet, orally, once daily.

Intervention Type: DRUG

liraglutide

0.6 mg by subcutaneous (pen) injection, once daily, on Days 1-7; up-titrated on Day 8 to 1.2 mg daily. At Week 12, dose may be increased to 1.8 mg once daily for participants who did not meet protocol-specified glycemic goals.

Intervention Type: DRUG

glimepiride

starting dose of 1 mg tablet (up-titrated as needed), once daily, as needed, after Week 12.

Intervention Type: DRUG

metformin

metformin tablets at a dose of ≥1500 mg per day

Intervention Type: DRUG

Other Intervention Names

MK-0431, Januvia®, Tesavel®, Xelevia®, Ristaben®; Victoza®; Amaryl®; Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®

Eligibility Criteria

Inclusion Criteria

• Type 2 diabetes mellitus.
• On stable dose of metformin monotherapy at a dose of at least 1500 mg per day for at least 12 weeks and a hemoglobin A1C ≥7.0% and ≤11.0%.
• Capable of using a liraglutide pen device.

Exclusion Criteria

• History of Type 1 Diabetes mellitus.
• Use of any oral antihyperglycemic agent (AHA) besides metformin, within the prior 12 weeks of screening.
• Cardiovascular disorders within the past 3 months including acute coronary syndrome or new or worsening symptoms of coronary heart disease, coronary artery intervention, stroke, or transient ischemic neurological disorder.
• Impaired liver function.
• Impaired kidney function.
• History of malignancy or clinically important hematological disorder that requires disease-specific treatment (chemotherapy, radiation therapy, surgery) or, in the opinion of the investigator, is likely to recur during the duration of the study.
• History of leukemia, lymphoma, aplastic anemia, myeloproliferative or myelodysplastic diseases, thrombocytopenia, or malignant melanoma, regardless of the time since treatment.
• Pregnancy or breastfeeding, or intention to become pregnant or donate eggs within the projected duration of the study.
• Participation in another study with an investigational drug or device within 12 weeks prior to screening.
• History of hypersensitivity or any contraindication to sitagliptin, liraglutide, glimepiride, or metformin based upon the labels of the country of the investigational site.
• Participation in a weight loss program and not yet in maintenance phase, or starting of a weight loss medication (such as orlistat or phentermine) within the prior 8 weeks.
• Surgery within the prior 4 weeks or major surgery planned during the study.
• Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2).
• User of recreational or illicit drugs or recent history (within the last year) of drug abuse or increased alcohol consumption.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

Charbonnel B, Steinberg H, Eymard E, Xu L, Thakkar P, Prabhu V, Davies MJ, Engel SS. Efficacy and safety over 26 weeks of an oral treatment strategy including sitagliptin compared with an injectable treatment strategy with liraglutide in patients with type 2 diabetes mellitus inadequately controlled on metformin: a randomised clinical trial. Diabetologia. 2013 Jul;56(7):1503-11. doi: 10.1007/s00125-013-2905-1. Epub 2013 Apr 19.

Reference Type: DERIVED

PMID: 23604551 (View on PubMed)

Other Identifiers

0431-403

Identifier Type: -

Identifier Source: org_study_id