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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: liraglutide; Drug: metformin; Drug: glimepiride; Drug: sitagliptin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01296412

0431-403

Details and patient eligibility

About

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.

Enrollment: 653 patients

Sex: All

Ages: 18 to 79 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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653 participants in 2 patient groups

Sitagliptin +/- glimepiride

Experimental group

Description:

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.

Treatment:

Drug: glimepiride

Drug: sitagliptin

Drug: metformin

Liraglutide

Active Comparator group

Description:

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.

Treatment:

Drug: metformin

Drug: liraglutide