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

NCT01296412 | Completed Phase 3 Results

• 1 other identifier: 0431-403
• Study Type: interventional
• Target: 653
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Hemoglobin A1c (A1C)

  A1C is measured as percent. Thus, this change from baseline reflects the Week 26 A1C percent minus the Week 0 A1C percent.

  Baseline and Week 26

Secondary Outcomes (3)

• Change From Baseline in Fasting Plasma Glucose (FPG)

  Baseline and Week 26

• Percentage of Participants Reaching A1C Goal of <7.0%

  Week 26

• Percentage of Participants Reaching A1C Goal of <6.5%

  Week 26

Study Arms (2)

Sitagliptin +/- glimepiride

EXPERIMENTAL

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.

Drug: sitagliptin; Drug: glimepiride; Drug: metformin

Liraglutide

ACTIVE COMPARATOR

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.

Drug: liraglutide; Drug: metformin

Interventions

sitagliptin DRUG

100 mg tablet, orally, once daily.

Also known as: MK-0431, Januvia®, Tesavel®, Xelevia®, Ristaben®

Sitagliptin +/- glimepiride

liraglutide 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.

Also known as: Victoza®

Liraglutide

glimepiride DRUG

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

Also known as: Amaryl®

Sitagliptin +/- glimepiride

metformin DRUG

metformin tablets at a dose of ≥1500 mg per day

Also known as: Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®

Liraglutide; Sitagliptin +/- glimepiride

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 23604551 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Sitagliptin Phosphate; Liraglutide; glimepiride; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2011
• First Posted: February 15, 2011
• Study Start: March 11, 2011
• Primary Completion: February 29, 2012
• Study Completion: February 29, 2012
• Last Updated: June 9, 2017
• Results First Posted: March 15, 2013

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will share