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.
Insulin glargine did not show significant benefits over usual care in terms of time in very low range or target range for children and young adults with type 1 diabetes in low-resource settings.
Where it sits
this study against the rest of the dulaglutide corpusSummary and findings
This study assessed the effects of insulin glargine compared to usual care (isophane insulin or premixed 70/30) in children and young adults with type 1 diabetes in low-resource settings. A total of 400 participants aged 7-25 years were randomly assigned to receive either treatment for 6 months. No significant differences were found in time spent in very low range or target range between the two groups.
Abstract
<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>The Leona M. and Harry B. Helmsley Charitable Trust.
Background
This study addresses the effectiveness of insulin glargine compared to human isophane insulin in managing type 1 diabetes among children and young adults in low-resource settings. Previous research has indicated varying outcomes for different insulin types, but specific data in low-income and middle-income countries is limited. Understanding the efficacy of insulin glargine in this population is crucial for optimizing diabetes management.
Methods
HumAn-1 was a multicenter, open-label, randomized controlled trial involving participants aged 7-25 years with type 1 diabetes. A total of 400 participants were randomly assigned to receive either insulin glargine or usual care, with doses varying by individual. The study primarily measured time in very low range and time in target range using continuous glucose monitors over a 6-month period.
Results
At 6 months, the mean time in very low range was 3.6% in the glargine group and 3.4% in the usual care group, with an adjusted mean difference of 0.22% (p=0.63). The mean time in target range was 40.5% for glargine and 38.1% for usual care, with an adjusted mean difference of 0.55% (p=0.71). Serious adverse events were reported in 3% of the glargine group and 6% of the usual care group.
Interpretation
The findings indicate no significant differences in time spent in very low or target glucose ranges between insulin glargine and usual care. While the study's results are statistically significant, the clinical relevance of the differences observed is questionable given the small effect sizes. Limitations such as the open-label design and the specific demographic may affect the applicability of these results to broader populations.
Key findings
- Mean time in very low range was 3.6% (SD 5.6) in the glargine group and 3.4% (SD 4.3) in the usual care group, p=0.63.
- Adjusted mean difference in time in very low range was 0.22% (97.5% CI -0.83 to 1.27, p=0.63).
- Mean time in target range was 40.5% (SD 18.4) for glargine and 38.1% (SD 18.1) for usual care, p=0.71.
- Adjusted mean difference in time in target range was 0.55% (97.5% CI -2.78 to 3.89, p=0.71).
- Serious adverse events occurred in 3% of participants in the glargine group and 6% in the usual care group.
Limitations
- Open-label design may introduce bias.
- Conducted at three sites, limiting generalizability.
- No long-term follow-up reported.