Highlights
- The HumAn-1 trial, conducted in Bangladesh and Tanzania, is the first large RCT comparing insulin glargine with human isophane insulin in children and young adults with type 1 diabetes (T1D) in resource-limited settings.
- No significant differences were observed between glargine and human insulin in time spent in serious hypoglycemia (<54 mg/dL) or time in glucose target range over 6 months.
- Serious adverse events were uncommon across both groups, with a slightly lower incidence in the glargine group.
- These findings support continued use of human insulins, which are more affordable and widely available, without compromising safety or glycemic control.
Background
Type 1 diabetes remains a chronic, life-long condition characterized by autoimmune destruction of pancreatic beta cells requiring lifelong insulin therapy. Globally, the burden of T1D in children and young adults is rising, particularly in low- and middle-income countries (LMICs) where healthcare resources are limited and insulin availability and affordability represent major barriers to optimal management.
Human insulins, including intermediate-acting preparations such as isophane insulin (NPH), have been the mainstay of basal insulin therapy in these settings due to lower cost and established use. However, prolonged fasting hypoglycemia and glycemic variability associated with human insulin have spurred development of analogue insulins (eg, insulin glargine), which provide more stable basal coverage and potentially reduce hypoglycemia. Although evidence from high-income countries favors analogue insulins for glucose control and hypoglycemia risk reduction, it is unclear whether these benefits translate to children and young adults with T1D living in low-resource contexts where multiple socioeconomic and healthcare factors influence outcomes.
Key Content
Evidence from the HumAn-1 Trial
The HumAn-1 trial (Luo et al., 2026) is a multicenter, open-label, randomized controlled trial conducted at one site in Bangladesh and two in Tanzania. It enrolled 400 participants aged 7-25 years with clinically diagnosed T1D, randomized 1:1 to receive insulin glargine (Basaglar) or usual care comprising isophane insulin or premixed 70/30 human insulin.
Basal insulin administration was tailored and reflected clinical discretion, with glargine typically dosed subcutaneously before bedtime. The primary co-outcomes, assessed by blinded continuous glucose monitoring at 6 months, were percentages of time in very low glucose range (<3 mmol/L or 54 mg/dL) and time in target range (3.9-10 mmol/L or 70-180 mg/dL). These endpoints are critical markers of hypoglycemia risk and glycemic control, respectively.
Results showed no statistically significant differences between the glargine and usual care groups for time in very low glucose range (3.6% vs. 3.4%, adjusted mean difference 0.22%, p=0.63) or time in target range (40.5% vs. 38.1%, adjusted mean difference 0.55%, p=0.71). Serious adverse events were rare in both groups, with fewer events in the insulin glargine arm (3% vs. 6%). These data suggest that insulin glargine did not confer added benefit over human insulins in the studied population within a 6-month timeframe.
Supporting and Complementary Literature
While the HumAn-1 trial directly compares analogue versus human insulin in LMIC pediatric populations, additional evidence highlights other challenges and solutions to insulin therapy in resource-constrained contexts. For example, a 2021 pilot randomized study in Brazil investigated therapeutic play interventions to improve insulin self-injection technique among children with T1D, underscoring the critical role of education and self-management capacity in these settings (de Oliveira et al., 2021). The intervention improved short-term injection technique but did not change longer-term self-injection practices, illustrating the multifactorial determinants of glycemic outcomes beyond insulin pharmacology.
Outside low-resource settings, trials have demonstrated that long-acting analogue insulins reduce nocturnal and severe hypoglycemia risks, and increase time-in-range compared to NPH insulin, particularly when combined with modern insulin delivery and glucose monitoring technology (Weissberg-Benchell et al., 2020; Hanas et al., 2019). However, these benefits have not been consistently replicated in LMICs, where access to advanced diabetes care technology and diabetes education is limited.
Comparative Safety and Patient-Centered Factors
Both insulin types demonstrated good safety profiles in HumAn-1. The incidence of serious adverse events such as severe hypoglycemia or diabetic ketoacidosis was low, reflecting well-conducted clinical follow-up despite resource constraints.
From a patient-centered perspective, analogue insulins provide more predictable pharmacodynamics, but require reliable cold chain storage and may incur higher costs, potential barriers in low-resource settings. Human insulins, while less physiologically stable, remain accessible and affordable, importantly impacting adherence and continuity of care.
Expert Commentary
The HumAn-1 trial addresses a critical gap in evidence by studying insulin analogues versus human insulins in children and young adults with T1D in under-resourced environments. Contrary to expectations shaped by data in high-income countries, this well-powered RCT demonstrated no superiority of insulin glargine over human isophane insulin for glycemic control or hypoglycemia mitigation at six months.
Possible explanations include:
- Differences in dosing, insulin regimen complexity, or adherence due to healthcare access variations.
- Limited availability of optimization tools like intensive glucose monitoring and structured patient education.
- The underlying metabolic and nutritional milieu in LMIC populations may modulate insulin pharmacodynamics.
Importantly, this evidence cautions against wholesale adoption of costlier analogue insulin formulations in contexts where human insulins remain effective and critical for therapy access.
Clinical guidelines, including the ISPAD and WHO, emphasize the paramount importance of sustained insulin availability, education, and individualized care over choice of insulin type in resource-limited settings. These findings reinforce that principle, supporting efforts to improve healthcare delivery infrastructure alongside medication access.
Conclusion
The HumAn-1 multicenter randomized trial provides robust evidence that insulin glargine offers no significant advantage over human isophane insulin in reducing serious hypoglycemia or enhancing time-in-range among children and young adults with T1D in low-resource settings at six months. This underscores the continued viability of human insulin regimens in such populations.
Improving outcomes in LMICs will require multifaceted strategies encompassing affordable insulin supply, comprehensive diabetes education, self-management support, and scalable glucose monitoring approaches tailored to healthcare realities. Future research should explore longer-term effects, regimen optimization, and implementation of integrated care models that balance clinical efficacy with economic feasibility in resource-constrained settings.
References
- Luo J, et al. Human versus analogue insulin for children and young adults with type 1 diabetes in low-resource settings (HumAn-1): a multicentre, open-label, randomised controlled trial. Lancet Diabetes Endocrinol. 2026 Jul 6. doi:10.1016/S2213-8587(26)00097-5. PMID: 42409045.
- de Oliveira VFR, et al. Therapeutic play to teach children with type 1 diabetes insulin self-injection: A pilot trial in a developing country. J Spec Pediatr Nurs. 2021 Jan;26(1):e12309. doi:10.1111/jspn.12309. PMID: 32945620.
- Hanas R, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Assessment and Monitoring of Glycemic Control in Children and Adolescents With Diabetes. Pediatric Diabetes. 2019;20(S27):52-63. doi:10.1111/pedi.12779.
- Weissberg-Benchell J, et al. Clinical efficacy and safety of long-acting insulin analogs in children and adolescents with Type 1 diabetes: A systematic review and meta-analysis. Diabetes Care. 2020;43(5):1086-1093. doi:10.2337/dc19-1908.