Trial Supports Glargine Use in Resource-Limited Type 1 Diabetes Care, With Benefits Emerging at 12 Months
核心洞察
A randomized trial of 400 participants aged 7–25 with Type 1 diabetes (搜索) in Bangladesh and Tanzania found no significant difference between insulin glargine and human insulin in primary glucose outcomes at six months.
At 12 months, glargine was associated with less time in the very low glucose range and fewer nocturnal hypoglycemic events than usual care.
Glargine was also linked to lower total daily insulin use and fewer injections per day, factors relevant to patients, families, and health systems.
A randomized clinical trial led by University of Pittsburgh researchers and published in The Lancet Diabetes & Endocrinology adds nuance to the question of whether older human insulins are as effective as insulin analogues in low-resource settings. The trial, which enrolled 400 participants with Type 1 diabetes (搜索) ages 7 to 25 in Bangladesh and Tanzania, found that the long-acting analogue insulin glargine was associated with less time spent in dangerous hypoglycemia and fewer nighttime low blood sugar events — but those benefits did not emerge until a year into the trial.
"The real question is not simply whether newer insulin is better, but whether the benefits we observed are compelling enough to inform purchasing, access and guideline decisions in places where choices are constrained," said Jing Luo, M.D., M.P.H., lead author and associate professor of medicine at the University of Pittsburgh. "That is the conversation this study helps move forward."
Trial Design and Primary Outcomes
The HumAn-1 trial studied a population often underrepresented in insulin research, enrolling 400 children and young adults aged 7 to 25 with Type 1 diabetes (搜索) in lower-resource settings. Participants were recruited in Bangladesh and Tanzania and randomly assigned to insulin glargine or usual care with intermediate-acting human insulin, including NPH or premixed 70/30 insulin.
At six months, researchers found no evidence of differences between the insulin analogue glargine and older human insulin in the trial's co-primary outcomes: time spent in very low glucose range and time spent in the target glucose range. Mean time in the very low glucose range was 3.6% with glargine and 3.4% with usual care, while mean time in the target glucose range was 40.5% with glargine and 38.1% with usual care. The adjusted differences were not statistically significant.
Benefits Emerging at 12 Months
At 12 months, however, participants assigned to glargine spent less time in very low glucose range and had fewer nocturnal hypoglycemic events than those assigned to usual care. Researchers did not find meaningful differences in time in range, HbA1c, diabetic ketoacidosis, severe hypoglycemic events, or symptomatic hypoglycemic events at 12 months.
Although glargine did not improve the study's primary outcomes at six months, the 12-month data suggest that benefits related to serious hypoglycemia may emerge more gradually in real-world, low-resource care settings. Glargine was also associated with lower total daily insulin use and fewer injections per day, factors that may matter to patients, families, and health systems alike.
Global Context and Access
The World Health Organization added long-acting insulin analogues such as glargine to its Model List of Essential Medicines in 2021. Still, Type 1 diabetes (搜索) care remains profoundly unequal worldwide. Of an estimated 9.5 million people living with Type 1 diabetes globally, about 3.2 million are treated exclusively with older human insulins, most of them in low- and middle-income countries. While long-acting insulin analogues such as glargine are widely used in higher-income settings, their higher cost and limited availability have slowed broader adoption elsewhere.
"In many parts of the world, children do not have access to the therapies considered standard elsewhere," said Luo. "These findings add new data to a global debate over whether health systems with constrained resources should prioritize access to newer insulin formulations despite their higher cost."
Serious adverse events were uncommon in both groups, although numerically fewer occurred in the glargine group. The findings do not establish that human insulin is universally equivalent to analogue insulin; rather, they suggest that simply replacing intermediate-acting human insulin with glargine may not automatically deliver large glucose improvements in every setting.
Implications for Clinical Decision-Making
The results should not be interpreted as evidence that the advantages of analogue insulins have disappeared. Long-acting analogues such as insulin glargine and insulin degludec generally provide flatter and more predictable basal coverage, while rapid-acting analogues such as insulin lispro and insulin aspart act faster than regular human insulin around meals. NPH insulin (搜索), by contrast, has a more pronounced peak, which can increase the possibility of unexpected or nighttime hypoglycemia.
For a child experiencing recurrent nocturnal hypoglycemia with NPH, switching to a long-acting analogue may provide an important clinical advantage. However, another patient may be doing well with human insulin and have reliable access to it at an affordable price; switching that person to a more expensive product without a clear clinical reason may provide limited additional value.
Researchers say additional study is needed to better understand longer-term glycemic outcomes after patients in low-resource settings switch from older human insulin to analogue insulin. The study was funded by the Leona M. and Harry B. Helmsley Charitable Trust.