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

Phase 4

Active, not recruiting

Interventions: Drug: NPH or premixed 70/30 (human insulin)
Drug: Insulin Glargine

Brief Summary: 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.

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.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

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

Arm && Interventions

Group	Intervention	Description
NPH or premixed 70/30 (human insulin)	NPH or premixed 70/30 (human insulin)	NPH or premixed 70/30 (human insulin)
Glargine	Insulin Glargine	Insulin glargine (long-acting insulin analogue)

Primary Outcome Measures

Name	Time	Method
Time-in-range (TIR)	6 months after randomization	% between 70 and 180mg/dl inclusive, averaged across two CGM sensors
Time-in-serious hypoglycemia	6 months after randomization	% spent less than 54mg/dl, averaged across all daily measures averaged across two CGM sensors

Secondary Outcome Measures

Name	Time	Method
Nocturnal hypoglycemic events	6 months after randomization	Number of events (defined as \>=15mins in duration \< 70mg/dl) between 1200 and 0600
Time-in-hypoglycemia	6 months after randomization	% spent less than 70mg/dl
Rate of severe hypoglycemic events	6 months after randomization	Events requiring the assistance of an external third party person
Time-above-range	6 months after randomization	% spent greater than 180mg/dl
Glycemic control (HbA1c)	baseline, 3, 6, 9 and 12 months after randomization	Mean HbA1c lab result
Quality of Life (e.g. PedsQL Pediatric Quality of Life Inventory)	Baseline and at 6 and 12 months after randomization	The PedsQLTM 3.2 Diabetes Module is composed of 33 items comprising 5 dimensions for ages 8- 45 years. Items are scaled on a 5-point scale from 0 (never) to 4 (almost always). Scores are transformed on a scale range from 0 to 100. The total score is the sum of all the items over the number of items answered on all scales.
Rate of Diabetic Ketoacidosis	6 months after randomization	Hospitalization or Emergency Room Visit with primary diagnosis of Diabetic Ketoacidosis. This will be measured by self-report and confirmed through review of hospital records

Locations (3): BIRDEM Hospital
🇧🇩
Dhaka, Bangladesh
Sekou-Toure Hospital
🇹🇿
Mwanza, Tanzania
Bugando Medical Center
🇹🇿
Mwanza, Tanzania