Toujeo Versus NPH Self-titration Study

A Pilot Study to Describe the Glycaemic Variability of Insulin Glargine 300U/ml Versus NPH (Neutral Protamine Hagedorn) in the Insulin-naïve Type 2 Diabetes Patients Following a Patient-adjusted Insulin Algorithm in Hong Kong

This is a 24 week, multicentre, prospective, randomized, controlled, parallel-designed (1:1) pilot study.The study will compare glycemic variability in patients treated with insulin glargine U300/ml insulin versus conventional (NPH) insulin using a self titration algorithm.50 type 2 diabetes patients who are newly started on insulin will be recruited. They will be randomly allocated to either insulin glargine U300 or NPH insulin for 26 weeks. All subjects will follow a insulin-self titration algorithm. The study will consist of 9 visits over 26 weeks. Blood glucose variability will be collected by CGM for 7 consecutive days at baseline (week -1) and at week 24.Secondary endpoints other than data on glycemic variability, including HbA1c, fasting plasma glucose, inflammatory markers will be measured during three periods (week 0, week 12 and week 24).

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Insulin Glargine 300 UNT/ML; Drug: Neutral protamine hagedorn insulin

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• Hong Kong
  • Shatin
    • Hong Kong, Shatin, Hong Kong
      • Prince of Wales Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 2 diabetic suboptimally controlled on their previous antidiabetic treatment

  • 18 ≤ age ≤ 75
  • Stable dose of oral antidiabetic treatment for > 8 weeks
  • The number of OADs that the patients used should be "3" or less
  • HbA1c level > 7.0% and < 10%
  • Fasting plasma glucose > 8mmol/L and <15mmol
  • BMI < 40 kg/m2
  • Patient who is capable and willing to perform regular SMBG
  • Patient who is capable and willing for insulin injection
  • Confirmed written consent
  • Insulin naïve

Exclusion Criteria:

• Participation in a clinical trial with any investigational drug used with curative intent and within 30 days prior to study entry
• Patient known to have hypoglycaemia unawareness or recurrent major hypoglycaemia
• Any product containing prandial insulin
• Concomitant medication known to interface with glucose metabolism (such as systematic steroids)
• Change in dose of non-insulin anti-diabetic treatment or initiation of new anti-diabetic medications in the last 8 weeks prior to screening
• Patients treated with steroid or nonsteroidal anti-inflammatory drugs
• Patient who had experienced an acute concurrent illness during the 3-month period before the investigation
• Patient with hepatic disease and end-stage renal disease
• Patients unable to comply with follow-up visits
• Pregnant or breastfeeding women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active; Insulin glargine 300U/ml	Drug: Insulin Glargine 300 UNT/ML; Self titration of insulin glargine U300
Active Comparator: Control; Neutral Protamine Hagedorn insulin	Drug: Neutral protamine hagedorn insulin; Self titration of NPH insulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycemic variability	Standard deviation of glucose from continuous glucose monitoring	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycemic variability	Mean Amplitude of Glycemic excursions and Means of Daily Differences	24 weeks
Percentage time in target	Percentage of time <3.0mmol/L and >10.0mmol/L	24 weeks
Glycated haemoglobin	HbA1c	24 weeks
Fasting blood glucose	FPG	24 weeks
Incidence of hypoglycemia	Overall incidence of hypoglycemia and nocturnal hypoglycemia	24 weeks
Proportion of patients achieving HbA1c <7.0%	Proportion of patients achieving HbA1c <7.0% at week 24 without confirmed hypoglycemia	24 weeks
Treatment satisfaction	ITSQ questionnaire	24 weeks
Inflammatory markers	change in hs C reactive protein	24 weeks
Heart rate variability	Change in heart rate variability	24 weeks

Collaborators and Investigators

• Sponsor: Elaine Chow
• Collaborators: Sanofi

Publications and helpful links

General Publications

• Semlitsch T, Engler J, Siebenhofer A, Jeitler K, Berghold A, Horvath K. (Ultra-)long-acting insulin analogues versus NPH insulin (human isophane insulin) for adults with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2020 Nov 9;11(11):CD005613. doi: 10.1002/14651858.CD005613.pub4.
• Ling J, Poon EWM, Yang A, Yeung T, Loo K, Ozaki R, Ma RCW, Luk AOY, Kong APS, Chan JCN, Chow E. Glycemic Variability and Time in Range During Self-titration of Once Daily Insulin Glargine 300 U/ml Versus Neutral Protamine Hagedorn Insulin in Insulin-naive Chinese Type 2 Diabetes Patients. Diabetes Ther. 2021 May;12(5):1399-1413. doi: 10.1007/s13300-021-01046-6. Epub 2021 Mar 18.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Actual): December 17, 2019
• Study Completion (Actual): May 1, 2020

Study Registration Dates

• First Submitted: December 26, 2017
• First Submitted That Met QC Criteria: December 26, 2017
• First Posted (Actual): January 3, 2018

Study Record Updates

• Last Update Posted (Actual): August 3, 2021
• Last Update Submitted That Met QC Criteria: August 2, 2021
• Last Verified: August 1, 2021

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; Coagulants; Heparin Antagonists; Insulin; Insulin, Globin Zinc; Insulin Glargine; Insulin, Isophane; Isophane Insulin, Human; Isophane insulin, beef; Protamines
• Other Study ID Numbers: GLARGL08588

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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