Human Versus Analogue Insulin for Youth With Type 1 Diabetes in Low-Resource Settings (HumAn-1)

Human Versus Analogue Insulin for Youth With Type 1 Diabetes in Low-Resource Settings: A Randomized Controlled Trial

The primary objective of this trial is to determine whether insulin glargine reduces the risk of serious hypoglycemia or improves Time in Range at 6 months when compared against standard of care human insulin (e.g. NPH or premixed 70/30) among youth living with type 1 diabetes (T1D) in low resource settings.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 1; Type 1 Diabetes
• Intervention / Treatment: Drug: Insulin Glargine; Drug: NPH or premixed 70/30 (human insulin)

Detailed Description

Long-acting insulin analogues have become a de-facto standard of care for patients with T1D living in high-income countries. Unfortunately, insulin analogues remain unavailable or unaffordable for much of the global population. In both 2017 and 2019, applications to add long-acting insulin analogues to the WHO's Model List of Essential Medicines (EML) were rejected due to insufficient evidence of superiority and an unfavorable cost-effectiveness profile when compared against older, less expensive, human insulins (e.g., NPH insulin and premixed 70/30 insulin). In 2021, long-acting insulin analogues were added to the EML but the decision remains controversial since the WHO concluded that "magnitude of clinical benefit of long-acting insulin analogues over human insulin for most clinical outcomes was small." Moreover, studies that compare long-acting insulin analogues versus human insulins conducted in high-income settings may not generalize to children and young adults living with T1D in very low-resource settings.

To address this unmet need, Pitt has partnered with Brigham and Women's Hospital, The London School of Hygiene and Tropical Medicine, the Clinton Health Access Initiative and Life For a Child to conduct a randomized controlled trial comparing insulin glargine, a long-acting analogue insulin, against intermediate human insulin among 400 children and young adults living with T1D in a lower resource setting.

Note: In preparation for results submission, we made minor changes to the outcomes sections to reflect what is listed in the protocol.

For Primary Outcomes #1 and #2, and Secondary Outcomes #3,#4, #5, #7, #8: we added 12 months measurements (in addition to the 6 months measurement). We updated Secondary Outcome #9 to specify the PedsQL Diabetes Symptoms Score. We added Secondary Outcome #10 to include the PedsQL Diabetes Management Score. We added Secondary Outcome #11 for ITSQ scores.

• Study Type: Interventional
• Enrollment (Actual): 400
• Phase: Phase 4

Contacts and Locations

Study Locations

• Bangladesh
  • Dhaka, Bangladesh
    • BIRDEM Hospital
• Tanzania
  • Mwanza, Tanzania
    • Bugando Medical Center
  • Mwanza, Tanzania
    • Sekou-Toure Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 25 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Children and young adults (age 7-25)
2. Have a clinical diagnosis of type 1 diabetes (T1D)

Exclusion Criteria:

1. Prior use of any insulin analogue
2. Patients (or parents for children <18 years old) who refuse to or cannot provide informed consent
3. Who are currently pregnant or plan to become pregnant over the next year
4. Who have previously used a continuous glucose monitor (CGM) for glucose monitoring
5. Who were first diagnosed with T1D less than 12 months ago
6. Who is diagnosed with severe malnutrition

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: Glargine; Insulin glargine (long-acting insulin analogue)	Drug: Insulin Glargine; Formulation: Available as a clear liquid in a glass cartridge (1 cartridge =3ml=300 units). Route: Reusable pen Amount of each dose: varies depending on baseline basal insulin needs Dose escalation scheme: Participants randomly assigned to glargine will start with a dose that is generally equal to 80% of their total basal human insulin dose prior to the switch (per ISPAD guidelines and the switching guide developed by Life for a Child with the guidance of Dr. Ragnar Hanas and two other ISPAD members familiar with less-resourced settings). Frequency of dose: once per day (usually administered before bedtime) Duration of therapy: 12 months
Active Comparator: NPH or premixed 70/30 (human insulin)	Drug: NPH or premixed 70/30 (human insulin); Formulation: Available as a liquid in a glass cartridge (3ml=300IU) or as liquid in a prefilled, disposable pen (3ml=300IU). Route: Bangladesh = reusable pens; Tanzania = disposable pens Amount of each dose: varies depending on baseline basal insulin needs (per usual care or treating clinician) Frequency of dose: once or twice per day (per usual care or treating clinician) Duration of therapy: 12 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-in-serious Hypoglycemia	% time spent less than 54 mg/dl averaged across all daily measures. For 6-month outcome, these data were averaged across two CGM sensors (placed at 6 and 6.5 months). For 12-month outcome, these data were from one CGM sensor placed at 11.5 months.	6 and 12 months after randomization
Time-in-range (TIR)	% time spent between 70 and 180mg/dl inclusive averaged across all daily measures. For 6-month outcome, these data were averaged across two CGM sensors (placed at 6 and 6.5 months). For 12-month outcome, these data were from one CGM sensor placed at 11.5 months.	6 and 12 months after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin Treatment Satisfaction Questionnaire (ITSQ) Scores	The ITSQ is composed of 22 items. A total 22-item score is reported, and the items are also divided into five subscales: Regimen Inconvenience (5 items), Lifestyle Flexibility (3 items), Glycemic Control (3 items), Hypoglycemic Control (5 items), and Insulin Delivery Device Satisfaction (6 items). Items use 7-point Likert scale responses, ranging from 1 (positive, e.g. "No bother at all") to 7 (negative, e.g. "A tremendous bother"), though the specific response labels vary by question. Items were reverse scored and transformed to range from 0 to 100. Higher scores indicate higher treatment satisfaction.	Baseline and at 6 and 12 months after randomization
Time-in-hypoglycemia	% time spent less than 70mg/dl averaged across all daily measures. For 6-month outcome, these data were averaged across two CGM sensors (placed at 6 and 6.5 months). For 12-month outcome, these data were from one CGM sensor placed at 11.5 months.	6 and 12 months after randomization
Time-above-range	% time spent greater than 180mg/dl averaged across all daily measures. For 6-month outcome, these data were averaged across two CGM sensors (placed at 6 and 6.5 months). For 12-month outcome, these data were from one CGM sensor placed at 11.5 months.	6 and 12 months after randomization
Nocturnal Hypoglycemic Events	Number of events defined as ≥15 minutes in duration <70 mg/dL between midnight and 6:00 am; specifically, at least 2 sensor values <70 mg/dL that are ≥15 minutes apart plus no intervening values ≥70 mg/dL For 6-month outcome, these data were averaged across two CGM sensors (placed at 6 and 6.5 months). For 12-month outcome, these data were from one CGM sensor placed at 11.5 months.	6 and 12 months after randomization
Glycemic Control (HbA1c)	Mean HbA1c lab result reported as percent, which is typically how it is reported.	baseline, 3, 6, 9 and 12 months after randomization
Rate of Severe Hypoglycemic Events	Severe hypoglycemic events (requiring assistance of another person to correct) reported by participant per 1000 person-years	6 and 12 months after randomization
Rate of Diabetic Ketoacidosis (DKA)	Hospitalization or Emergency Room Visit (serious adverse event) with primary diagnosis of Diabetic Ketoacidosis. This was measured by self-report and confirmed through review of hospital records	6 and 12 months after randomization
Pediatric Quality of Life Inventory 3.2 Diabetes Module (PedsQL 3.2 DM) Diabetes Symptoms Score	Mean PedsQL 3.2 DM Diabetes Symptoms score. PedsQL 3.2 DM Diabetes Symptoms scale is composed of 15 items. All items use the same 5-point Likert response scale, with responses ranging from "never" (0) to "almost always" (4). Items are reverse scored and transformed on a scale ranging from 0 to 100. The score is the sum of all the items over the number of items answered. Higher scores indicate fewer diabetes symptoms and therefore improved diabetes-specific health-related quality of life (D-HRQoL).	Baseline and at 6 and 12 months after randomization
Pediatric Quality of Life Inventory 3.2 Diabetes Module (PedsQL 3.2 DM) Diabetes Management Score	Mean PedsQL 3.2 DM Diabetes Management score. PedsQL 3.2 DM Diabetes Management scale is composed of 18 items. All items use the same 5-point Likert response scale, with responses ranging from "never" (0) to "almost always" (4). Items are reverse scored and transformed on a scale ranging from 0 to 100. Higher scores indicate fewer diabetes management problems and therefore improved D-HRQoL.	Baseline and at 6 and 12 months after randomization

Collaborators and Investigators

• Sponsor: Jing Luo
• Collaborators: The Leona M. and Harry B. Helmsley Charitable Trust
• Investigators: Principal Investigator: Jing Luo, MD, MPH, University of Pittsburgh

Publications and helpful links

General Publications

• Foulds A, Josey C, Kehlenbrink S, Rollman BL, Chang CH, Lalama C, Ansbro E, Prust ML, Zabeen B, Ramaiya K, Ogle G, Chae SR, Luo J. Human versus Analogue Insulin for Youth with Type 1 Diabetes in Low-Resource Settings (HumAn-1): protocol for a randomised controlled trial. BMJ Open. 2025 Jan 30;15(1):e092432. doi: 10.1136/bmjopen-2024-092432.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2023
• Primary Completion (Actual): August 13, 2024
• Study Completion (Actual): March 19, 2025

Study Registration Dates

• First Submitted: October 28, 2022
• First Submitted That Met QC Criteria: November 4, 2022
• First Posted (Actual): November 14, 2022

Study Record Updates

• Last Update Posted (Estimated): September 10, 2025
• Last Update Submitted That Met QC Criteria: September 8, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Tanzania; Type 1 Diabetes; Bangladesh; Insulin Glargine; Insulin Analogue; Human Insulin
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Hyperinsulinism; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 1; Insulin Resistance; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Insulin, Long-Acting; Pancreatic Hormones; Insulin Glargine; Insulins
• Other Study ID Numbers: STUDY21110122

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified, summary level data will be shared with other researchers, upon request.
• IPD Sharing Time Frame: 3 years after the completion of the primary endpoint (Start 16 September 2024; End 16 September 2027)
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal, upon request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes