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

Abstract

Background: Human insulins including intermediate-acting human insulin (ie, isophane insulin) remain widely used for children and young people with type 1 diabetes, especially in low-resource settings. We aimed to assess whether insulin glargine reduces the risk of serious hypoglycaemia or improves time in range when compared against human isophane insulin among children and young people with type 1 diabetes in low-income and middle-income countries. Methods: HumAn-1 was a randomised, open label, parallel-group trial conducted at one site in Bangladesh and two sites in Tanzania. Participants aged 7–25 years with a clinical diagnosis of type 1 diabetes were randomly assigned (1:1) to receive insulin glargine (Basaglar, Eli Lilly, Indianapolis, IN, USA) or to continue usual care (ie, isophane insulin or premixed 70/30) for basal insulin coverage. Insulin glargine was administered subcutaneously, usually before bedtime. Isophane insulin or premixed 70/30 was administered once or twice per day, at the discretion of the treating clinician. Doses varied by participant. Randomisation was performed centrally and stratified by site. The coprimary outcomes, measured using blinded continuous glucose monitors at 6 months, were time in very low range (<3 mmol/L or 54 mg/dL) and time in target range (3·9 mmol/L to 10·0 mmol/L or 70 mg/dL to 180 mg/dL). The primary analysis was done for the overall intention-to-treat (ITT) population. The safety population included all participants who received at least one dose of study treatment and was analysed according to the treatment actually received. In this study, all participants received at least one dose of their randomly assigned intervention (ie, the ITT population is the same as the safety population). This trial is registered with ClinicalTrials.gov (NCT05614089). Findings: Between March 1 and Dec 19, 2023, we assessed 426 children and young people for eligibility. Of these, 400 (94%) were randomly assigned to receive either glargine (n=199) or usual care (n=201). At 6 months, the mean time in very low range was 3·6% (SD 5·6) in the glargine group and 3·4% (4·3) in the usual care group. After adjustment for prespecified baseline covariates, the adjusted mean difference was 0·22% (97·5% CI –0·83 to 1·27, p=0·63). The mean time in target range was 40·5% (SD 18·4) for glargine and 38·1% (18·1) for usual care. The adjusted mean difference was 0·55% (97·5% CI –2·78 to 3·89, p=0·71). Serious adverse events (SAEs) were uncommon, with a total of six SAEs among five (3%) of 199 participants in the glargine group and 14 SAEs among 13 (6%) of 201 participants in the usual care group. Interpretation: At 6 months, children and young people with type 1 diabetes living in low-resource settings randomly assigned to glargine had no evidence of effects on time in very low range and time in target range compared with those assigned to usual care. Funding: The Leona M. and Harry B. Helmsley Charitable Trust.