Efficacy of Sitagliptin and Glibenclamide on the Glucose Variability in Japanese Participants With Type 2 Diabetes Mellitus (MK-0431-355)

A Randomized, Open-label, Comparative Clinical Trial to Study the Efficacy of Sitagliptin and Glibenclamide in a Short Term Treatment on the Daily Glucose Variability Using Continuous Glucose Monitoring (CGM) in Japanese Patients With Type 2 Diabetes Mellitus

This is a study of the efficacy of sitagliptin and glibenclamide in a short-term treatment on the glucose variability using continuous glucose monitoring (CGM) in Japanese participants with type 2 diabetes mellitus (T2DM). The primary hypothesis is that treatment with sitagliptin will be superior to treatment with glibenclamide in the change from baseline in mean amplitude of glycemic excursions (MAGE) through continuous glucose monitoring (CGM) after 13 days of treatment.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Sitagliptin; Drug: Glibenclamide

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Japanese participants with a diagnosis of Type 2 diabetes mellitus

Exclusion Criteria:

• History of Type 1 diabetes mellitus or ketoacidosis
• History of insulin or thiazolidinedione (including fixed-dose drug combinations containing one of these drugs) in the 12 weeks before study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sitagliptin 50 mg; Sitagliptin 50 mg administered orally once daily before breakfast for 14 days.	Drug: Sitagliptin; Sitagliptin 50 mg orally once a day before breakfast for 14 days; Other Names: MK-0431
Active Comparator: Glibenclamide 2.50 mg TDD; Glibenclamide 1.25 mg administered orally twice daily (2.5 mg TDD) for 14 days. TDD = Total daily dose.	Drug: Glibenclamide; Glibenclamide 1.25 mg orally twice a day (2.5 mg/day) before breakfast and dinner for 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Amplitude of Glycemic Excursions (MAGE) at Day 13	MAGE is a popular metric for assessment of major (e.g., postprandial) glucose swings. MAGE is calculated as the average of differences between consecutive glucose peaks and nadirs greater than 1 standard deviation (SD) of 24-hour mean glucose. In this assessment, glucose levels were determined using continuous glucose monitoring (CGM) over 24 hours at Baseline and Day 13; CGM values were further corrected for blood glucose values obtained via participant-administered finger-stick. Least squares (LS) means values were derived from a constrained longitudinal analysis model. A negative (-) change from Baseline to Day 13 indicates improvement of the assessed outcome.	Baseline (Day -2) and Day 13

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Standard Deviation of Blood Glucose Levels	SD is a popular metric for assessment of postprandial glucose swings. The SD of all glycemic excursions over 24 hours (i.e., total of 288 glucose values over 24 hours) was determined for Baseline and Day 13. Original values were obtained using CGM and corrected for blood glucose values obtained via participant-administered finger-stick. LS mean values were derived from a constrained longitudinal analysis model. A negative (-) change from Baseline to Day 13 indicates improvement of the assessed outcome.	Baseline (Day -2) and Day 13
Change From Baseline in Maximum Incremental Postprandial Glucose Levels in Each Meal	The peak postprandial glucose level during the 3 hours post meal minus the preprandial glucose level 1 hour before meal was determined for corrected CGM values at Baseline and Day 13 for breakfast, lunch, and dinner. Meals were standardized with respect to total calories, and protein, fat, and carbohydrate composition as well as timing of administration. CGM values were corrected using a participant-administered finger-stick test for blood glucose. LS mean values were derived from a constrained longitudinal analysis model. A negative (-) change from baseline to Day 13 indicates better control of postprandial glucose.	Baseline (Day -2) and Day 13
Change From Baseline in 24-hour Mean Glucose Level	The mean glucose level over 24-hours at Baseline and Day 13 was determined using CGM values corrected for participant-administered finger-stick values. LS mean values were derived from a constrained longitudinal analysis model. A negative (-) change from Baseline to Day 13 indicates improvement of the assessed outcome.	Baseline (Day -2) and Day 13
Change From Baseline in Percentage of Hypoglycemic Values (Glucose Sensor Readings: < 70, <60, <50 mg/dL)	Hypoglycemia, defined as low blood glucose, is a common side effect of medications used to treat diabetes mellitus type 2. The percentage of hypoglycemic corrected CGM readings (sensor glucose <70, <60, <50 mg/dL) over a 24-hour period were determined at baseline and Day 13. CGM values were corrected using a participant-administered finger-stick test for blood glucose. LS mean values were derived from a constrained longitudinal analysis model. A negative (-) change from baseline to Day 13 indicates improvement in occurrence of hypoglycemia.	Baseline (Day -2) and Day 13

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Suzuki R, Eiki JI, Moritoyo T, Furihata K, Wakana A, Ohta Y, Tokita S, Kadowaki T. Effect of short-term treatment with sitagliptin or glibenclamide on daily glucose fluctuation in drug-naive Japanese patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2018 Sep;20(9):2274-2281. doi: 10.1111/dom.13364. Epub 2018 Jun 11.

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2015
• Primary Completion (Actual): December 15, 2015
• Study Completion (Actual): December 15, 2015

Study Registration Dates

• First Submitted: December 12, 2014
• First Submitted That Met QC Criteria: December 12, 2014
• First Posted (Estimate): December 17, 2014

Study Record Updates

• Last Update Posted (Actual): August 21, 2018
• Last Update Submitted That Met QC Criteria: July 23, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate; Glyburide
• Other Study ID Numbers: 0431-355; 152867 (Registry Identifier: JAPIC-CTI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf