Comparison of Thrice-Daily Premixed Human Insulin with Basal-Bolus Therapy Among Patients with Poorly Controlled Type 2 Diabetes Mellitus
February 27, 2025 updated by: Jamie Teoh Hong Im, Hospital Sultanah Aminah Johor Bahru
Comparison of Thrice-Daily Premixed Human Insulin with Basal-Bolus Therapy Among Patients with Poorly Controlled Type 2 Diabetes Mellitus: a Randomised Cross-Over Study
The goal of this cross-over study is to learn if thrice-daily (TDS) premixed human insulin (PHI) is as useful as basal-bolus (BB) therapy as an intensification treatment in people with poorly controlled type 2 diabetes mellitus (T2DM). The main questions it aims to answer are:
- To determine the efficacy of TDS PHI compared to BB insulin regimen by measuring HbA1c changes over 12 weeks.
- To determine the changes in fasting plasma glucose (FPG), the total daily dose (TDD) of insulin, weight changes, and hypoglycaemia rate, and to study the adherence rate to insulin injection between the two regimens over 12 weeks.
Researchers will compare TDS-PHI to BB regimen to see if the glycemic control, TDD of insulin, weight gain, hypoglycemia and adherence rate are the same.
Participants will:
- take TDS-PHI or BB for 12 weeks and cross over to the other regimen for another 12 weeks
- visit the clinic once every 4 weeks for checkups and tests
- keep a diary of their self-monitoring of blood glucose (SMBG), insulin doses, hypoglycaemic symptoms and blood glucose readings, and the number of times they miss insulin injections.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Thrice-daily (TDS) biphasic insulin analogues are suitable alternatives for intensifying insulin therapy, but the clinical use of TDS premixed human insulin (PHI) is unclear.
When people with type 2 diabetes mellitus (T2DM) require intensification of treatment, twice daily (BD) PHI is often intensified to a basal-bolus (BB) regimen, but compliance can be poor.
The investigators hypothesised that TDS PHI is as efficacious as BB therapy.
A cross-over study comparing TDS PHI with BB regimens among people with T2DM is conducted primarily aimed to evaluate and compare the efficacy of TDS PHI (Mixtard® 30) with the BB insulin regimen (Insulatard® once daily plus thrice daily prandial Actrapid®) in T2DM with inadequate glycaemic control on BD PHI and to assess the changes in FPG, TDD of insulin, weight changes, hypoglycaemia rate, and rate of adherence to insulin injection in local setting.
Participants receive TDS-PHI or BB for 12 weeks and cross over to the other regimen for another 12 weeks.
Glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), the total daily dose (TDD) of insulin, weight, hypoglycaemia, and adherence to insulin injections over 12 weeks are measured.
Study Type
Interventional
Enrollment (Actual)
44
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Penang
-
George Town, Penang, Malaysia, 10450
- Hospital Pulau Pinang
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Type 2 Diabetes patients
- Age 18 to 65 years
- HbA1c 8 to 12%
- Taking twice-daily (BD) premixed human insulin for at least 6 months
Exclusion Criteria:
- Age more than 65 years
- Had more than one episode of severe hypoglycaemia within six months
- Received treatment with systemic glucocorticoid therapy or glucose-lowering drugs other than metformin, DPP4 inhibitor and SGLT-2 inhibitor within the last three months
- Cardiac disease with a class III or class IV functional capacity
- Decompensated heart failure, unstable angina or myocardial infarction within the previous six months
- Renal insufficiency with serum creatinine more than 150umol/L
- Active liver disease or deranged liver function tests
- Untreated proliferative retinopathy or maculopathy
- Pregnant women
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Active Comparator: Group A (Mixtard® 30)
Participants start on TDS PHI (Mixtard® 30 TDS) and cross over to BB regimen (Insulatard® once daily plus thrice daily prandial Actrapid®) at 12 weeks (visit 4).
The initial TDD of insulin equals the baseline TDD of the participants' original insulin regimen and is distributed in a 40:20:40 ratio (breakfast, lunch, and dinner).
|
The clinical use of TDS premixed human insulin (PHI) is unclear.
In contrast, biphasic insulin analogue given thrice daily is a well-proven, safe and suitable alternative to an intensified insulin regimen.
Basal bolus regimen is considered a physiological form of treatment and the standard of care in clinical practice but the multiple daily injections often lead to poor compliance.
|
|
Active Comparator: Group B (Insulatard® and Actrapid®)
Participants start on BB regimen (Insulatard® once daily plus thrice daily prandial Actrapid®) and cross over to TDS PHI (Mixtard® 30 TDS) at 12 weeks (visit 4).
The initial TDD of insulin equals the baseline TDD of the participants' original insulin regimen and is split between Actrapid® and Insulatard® as 50 and 50 per cent, respectively.
Actrapid® is further divided equally across the meals.
|
The clinical use of TDS premixed human insulin (PHI) is unclear.
In contrast, biphasic insulin analogue given thrice daily is a well-proven, safe and suitable alternative to an intensified insulin regimen.
Basal bolus regimen is considered a physiological form of treatment and the standard of care in clinical practice but the multiple daily injections often lead to poor compliance.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Efficacy of TDS PHI compared to BB insulin regimen as assessed by changes in HbA1c measured in percentage
Time Frame: 12 weeks
|
12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Changes in FPG measured in mmol/l
Time Frame: 12 weeks
|
12 weeks
|
|
Changes in TDD of insulin measured in units
Time Frame: 12 weeks
|
12 weeks
|
|
Changes in weight measured in kilograms
Time Frame: 12 weeks
|
12 weeks
|
|
Changes in hypoglycemia rate as assessed by episodes per subject year
Time Frame: 12 weeks
|
12 weeks
|
|
Adherence to insulin injection as assessed by the frequency of missed doses per month
Time Frame: 12 weeks
|
12 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Jamie HI Teoh, MD, Hospital Pulau Pinang, Malaysis
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 1, 2020
Primary Completion (Actual)
January 14, 2021
Study Completion (Actual)
July 1, 2021
Study Registration Dates
First Submitted
February 17, 2025
First Submitted That Met QC Criteria
February 27, 2025
First Posted (Actual)
March 25, 2025
Study Record Updates
Last Update Posted (Actual)
March 25, 2025
Last Update Submitted That Met QC Criteria
February 27, 2025
Last Verified
February 1, 2025
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- NMRR-20-599-54337
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
product manufactured in and exported from the U.S.
No
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