The Korean TITRATION Study: Comparison of the Self-titration Methods for Glargine-300

A Korean, Single-center, Open-label, Randomized Study of Two Titration Algorithms With Insulin Glargine 300 Units/mL in Patients With Type 2 Diabetes Mellitus

The aim of this study is to demonstrate efficacy and safety of self-titration algorithm with Gla-300 using the INSIGHT algorithm (once daily by 1 unit) and the EDITION algorithm (once weekly by 3 units) in Korean patients with T2D.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Behavioral: Group 1; Behavioral: Group 2

Detailed Description

The primary objective of this study is to obtain efficacy and safety descriptive data on two different titration algorithms: the INSIGHT titration algorithm (self-titration of 1 unit/day) and the EDITION trial algorithm with insulin glargine 300 units/mL (GLA-300) when given as basal insulin in uncontrolled T2DM patients on basal insulin with or without non-insulin anti-hyperglycemic agent (NIAHA) or in insulin naïve patients.

In a Korean, single-center, type 2 diabetes patients with basal insulin therapy will be enrolled. They will be randomly assigned to either titration algorithm for GLA-300. After 12 weeks, the glycemic control, patients' satisfaction to the titration methods and healthcare providers' satisfaction to titration methods will be assessed.

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged ≥ 19 years
• Treated for T2D for at least 6 months
• Uncontrolled T2D
• Use of SMPG
• HbA1c > 7% and ≤ 10% in patients with a basal insulin (Gla-100, Gla-300, neutral protamine Hagedorn (NPH), and detemir) or HbA1c > 7% and ≤ 11% in insulin naive patients
• Signed informed consent

Exclusion Criteria:

• Type 1 diabetes mellitus
• Pregnancy or lactation
• Night-shift worker
• Unwilling to inject insulin or perform SMPG
• Treated with insulin other than basal insulin within the previous 3 months
• Not on stable dose of basal insulin (±20%) in the last 3 months
• Initiation or change in dose of oral anti-hyperglycemic agents in the last 3 months
• History of alcohol or drug abuse
• Active cancer or other significant comorbidities which the investigator would make the patients unsuitable for participating in the study
• Any clinically significant laboratory finding which the which the investigator would make the patients unsuitable for participating in the study
• Known drug allergy to insulin
• Not signed informed consent
• Incompletion of the study
• Participating in another clinical trial

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: Group 1; In group 1, the dose of Gla-300 will be titrated by the patients by 1 unit per day until achieving a fasting SMPG in the target range of 4.4 to 5.6 mmol/L (INSIGHT algorithm). Titration algorithms: Patients will be instructed to daily adjust their dose of Gla-300 based on fasting SMPG values. Fasting SMPG will be measured daily by the patient before breakfast and any intake of antihyperglycemic agents. Fasting SMPG in the range of; ≥ 5.6 mmol/L, increase 1 unit of Gla-300 dose; > 4.4 and ≤ 5.6 mmol/L, no change; < 4.4 mmol/L, reduce 1 unit of Gla-300 dose	Behavioral: Group 1; Patients will be instructed to daily adjust their dose of Gla-300 based on fasting SMPG values. Fasting SMPG will be measured daily by the patient before breakfast and any intake of antihyperglycemic agents. Fasting SMPG in the range of ≥ 5.6 mmol/L, increase 1 unit of Gla-300 dose, > 4.4 and ≤ 5.6 mmol/L, no change, < 4.4 mmol/L, reduce 1 unit of Gla-300 dose; Other Names: INSIGHT algorithm
Active Comparator: Group 2; In group 2, the dose of Gla-300 will be titrated by the patients based on the SMPG values of the last 3 days at least weekly, but no more often than every 3 days to achieve a fasting SMPG in the target range of 4.4 to 5.6 mmol/L (EDITION algorithm). Fasting SMPG (median of the last 3 days including current day) in the range of; ≥ 7.8 mmol/L, increase 6 units of Gla-300 dose; > 5.6 and < 7.8 mmol/L, increase 3 units of Gla-300 dose; > 4.4 and ≤ 5.6 mmol/L, no change; ≥ 3.3 and < 4.4 mmol/L, reduce 3 units of Gla-300 dose; < 3.3 mmol/L or occurrence of ≥ 2 symptomatic or 1 severe hypoglycemic episode in the preceding week, reduce 3 units of Gla-300 dose or at the discretion of the investigator	Behavioral: Group 2; Fasting SMPG (median of the last 3 days including current day) in the range of; 7.8 mmol/L, increase 6 units of Gla-300 dose, > 5.6 and < 7.8 mmol/L, increase 3 units of Gla-300 dose, > 4.4 and ≤ 5.6 mmol/L, no change,; 3.3 and < 4.4 mmol/L, reduce 3 units of Gla-300 dose, < 3.3 mmol/L or occurrence of ≥ 2 symptomatic or 1 severe hypoglycemic episode in the preceding week, reduce 3 units of Gla-300 dose or at the discretion of the investigator; Other Names: EDITION algorithm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients achieving fasting SMPG ≤ 5.6 mmol/L without hypoglycemia at 12 weeks	up to 12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in HbA1c (%)	up to 12 weeks
Fasting plasma glucose (mmol/L)	up to 12 weeks
Fasting SMPG (mmol/L)	up to 12 weeks
7-point SMPG (mmol/L)	up to 12 weeks
Proportion of patients at HbA1c ≤ 7%	up to 12 weeks
Change in insulin dose (IU)	up to 12 weeks
Change in body weight (kilogram)	up to 12 weeks
Hypoglycemia (number of patients)	up to 12 weeks
Adverse events	up to 12 weeks
Patient satisfaction to the insulin titration method (evaluated by prespecified questionnaire: DTSQs)	up to 12 weeks
Health care professionals' satisfaction to the insulin titration methods (evaluated by prespecirfied questionnaire: health care provider treatment satisfaction questionnaire)	up to 12 weeks

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Sanofi

Publications and helpful links

General Publications

• Bae JH, Ahn CH, Yang YS, Moon SJ, Kwak SH, Jung HS, Park KS, Cho YM. Efficacy and Safety of Self-Titration Algorithms of Insulin Glargine 300 units/mL in Individuals with Uncontrolled Type 2 Diabetes Mellitus (The Korean TITRATION Study): A Randomized Controlled Trial. Diabetes Metab J. 2022 Jan;46(1):71-80. doi: 10.4093/dmj.2020.0274. Epub 2021 Jun 16.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2017
• Primary Completion (Actual): January 17, 2020
• Study Completion (Actual): July 14, 2020

Study Registration Dates

• First Submitted: December 18, 2017
• First Submitted That Met QC Criteria: January 15, 2018
• First Posted (Actual): January 23, 2018

Study Record Updates

• Last Update Posted (Actual): October 22, 2020
• Last Update Submitted That Met QC Criteria: October 21, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Insulin
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: H-1708-078-878

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No