A Steadier Way to Keep Blood Sugar Up: New Trials of a Long-Lasting Glucagon for Babies Born With Too Much Insulin

Two randomised studies tested a small wearable pump delivering dasiglucagon in children with congenital hyperinsulinism, including newborns who could not come off intravenous sugar

Two clinical trials have tested a new medicine called dasiglucagon in children born with congenital hyperinsulinism, a rare condition in which the body makes too much insulin and blood sugar keeps falling dangerously low. In babies under one year old who depended on a sugar drip, the medicine cut the amount of intravenous sugar they needed by more than half. In older children treated at home, the results were more mixed.

Why low blood sugar in a newborn is treated as an emergency

Glucose is the brain's main fuel. When an adult's blood sugar drops, the body switches to a backup fuel made from stored fat. Insulin blocks that backup system. So in a baby whose pancreas releases insulin no matter how low the blood sugar goes, both fuel supplies shut down at once — and the brain, which is growing faster in the first months of life than at any other time, is left without energy. That is why neonatal teams treat these babies with an urgency that can surprise families, and why the goal is not simply "an acceptable number" but keeping the sugar reliably above a safe line at all hours.

The condition, and the two new studies

Congenital hyperinsulinism means the pancreas keeps producing insulin regardless of the blood sugar level. Families and specialist centres have said for years that the biggest problem is not the diagnosis but the shortage of medicines that actually work [1]. Two studies published recently were designed to test one possible answer. The first enrolled children aged three months to twelve years who were already receiving the best available care at home and were still having low sugars several times a week [2]. The second enrolled babies aged one week to twelve months who were still on an intravenous sugar drip in hospital and could not be weaned off it [3]. The two studies were deliberately built as companion pieces, covering opposite ends of the same problem.

The condition is rare. One careful estimate, based on how often genetic testing is requested, put the minimum rate in the United Kingdom at about 1 in 28,000 births [4]. In most children with a genetic cause, the fault lies in a tiny channel on the surface of the insulin-producing cells — a kind of switch that should tell the cell to stop releasing insulin when sugar is low. Changes in the two genes that build this switch, called ABCC8 and KCNJ11, account for the largest share of cases [5]. Under a microscope, the disease comes in different forms: sometimes only a small patch of the pancreas is affected ("focal"), sometimes the whole organ is ("diffuse"), and this distinction — not how severe the low sugars look — decides whether surgery can cure a child [6].

The reason for urgency is well documented. Brain scans of newborns who had symptomatic low blood sugar show recognisable patterns of injury, and those patterns line up with later difficulties in learning and development [7]. Because of this, paediatric hormone specialists recommend a higher, stricter safety target for babies with a confirmed hypoglycaemia condition than for the brief, self-correcting low sugars that many healthy newborns have in their first day or two [8].

What families faced before these trials

Until now the medicine cupboard has been almost bare. Only one drug, diazoxide, is formally licensed — and it works by opening the very switch that is broken in most children with a genetic cause, so for those children it simply does not work. Everything else has been borrowed from other conditions and used without a licence, each option carrying its own side effects [9]. Reviews of what might be coming next kept reaching the same conclusion: nothing had been designed to be given steadily, at home, over months [10].

When medicines failed, the remaining option was surgery to remove most of the pancreas. One specialist centre alone has performed 500 such operations, which gives a sense of how routine this pathway became [11]. For a child with the focal form, removing the affected patch can be a genuine cure. For a child with the diffuse form, it is a trade. Long-term follow-up of children who had this surgery found a high rate of diabetes needing insulin injections, alongside continuing learning and behavioural difficulties [12]. Parents were, in effect, being asked to choose between two chronic conditions.

There has long been an obvious candidate medicine. Glucagon is the hormone that does the opposite of insulin — it tells the liver to release stored sugar — and hospitals have used it intravenously for years to stabilise these babies. The problem was chemical, not biological: ordinary glucagon clumps together in water within hours, so it cannot be loaded into a small wearable pump. Dasiglucagon is a redesigned version of the same hormone, with seven building blocks swapped so that it stays stable in liquid form, and its behaviour in the body was worked out in adults before children were studied [13].

How the studies were done

In the study of babies [3], twelve infants took part at four specialist centres — one in Germany, one in the United Kingdom and two in the United States. Their median age was 38 days. All were receiving intravenous sugar through a central line at high rates. Each baby received dasiglucagon for 48 hours and a dummy infusion for 48 hours, in a random order, with neither parents nor doctors knowing which was which at the time. Afterwards, every baby received the real medicine openly for three weeks.

In the study of older children [2], thirty-two children took part at eleven hospitals in the United States, the United Kingdom, Germany and Israel. Half were given dasiglucagon by pump on top of their usual treatment for four weeks while the other half continued their usual treatment alone; then everyone received the medicine for four more weeks. Throughout, the children wore a continuous glucose monitor — a small sensor that reads sugar every five minutes — but the readings were hidden from everyone until the study ended, so they could not influence day-to-day decisions.

What the studies found

For the babies, the effect was clear and fast. On dasiglucagon they needed an average of 4.3 mg of intravenous sugar per kilogram each minute, compared with 9.5 on the dummy infusion — a reduction of more than half, achieved within two days [3]. They also needed about 31 grams less carbohydrate a day overall. In the three open weeks that followed, seven of the twelve babies came off intravenous sugar entirely within one week and ten of twelve within two weeks. Seven of those ten were still off it at the end of the study without having had pancreatic surgery, and four babies went home during the study period. Two babies did go on to have surgery.

For the older children, the answer depended on how low blood sugar was measured [2]. The study's main measurement was fingerprick tests done by families, and by that measure the medicine showed no clear advantage. But the hidden continuous sensor told a different story: episodes of low blood sugar fell by 43%, the total time spent with low sugar was roughly halved, and overnight lows — the ones nobody is awake to catch — fell by 61%. Part of the explanation is simple: families in the treatment group were testing about 25% more often, which finds more episodes and works against the medicine on a simple count. The sensor, checking every five minutes regardless, did not have that problem. It is important to be straight about this: these sensor findings were analysed after the fact rather than being the study's original question, so they are encouraging rather than proof.

Side effects were mostly what would be expected from a glucagon-type medicine. Vomiting was the most common, affecting five of sixteen treated children compared with one of sixteen on usual care alone. Skin rashes at and around the infusion site were more frequent, and two older children developed a specific rash known to occur with high glucagon levels; both were managed by lowering the dose rather than stopping. One child had to stop because their blood sugar swung too high. In the babies, no serious problem was linked to the medicine and none stopped treatment because of side effects.

What this means for families now

Dasiglucagon is not yet approved for congenital hyperinsulinism anywhere, so it is not something to ask for at your next appointment. What has changed is the direction of travel. For the first time, there is properly randomised evidence that a stable glucagon can be worn in a small pump, at home, by very young children, and that it substantially reduces the amount of sugar a baby needs by drip. Almost every family who took part chose to continue in a longer study afterwards — 31 of 32 older children and 11 of 12 babies — which is itself a meaningful signal about how the treatment felt to live with.

There is also a practical takeaway that does not depend on this medicine at all. Both studies showed that fingerprick testing misses a great deal of low blood sugar, particularly overnight. If your child has this condition and has never worn a continuous glucose sensor, it is a reasonable thing to raise with your team.

What researchers are working on next

Three questions remain open. Does the benefit last for years rather than weeks? Does it genuinely spare children from having most of their pancreas removed, or only delay it? And — the question families ask first — does keeping blood sugar steadier actually protect learning and development? Neither trial measured that, because both were too short. The long-term extension study that most participants joined is where the first answers should come from.

References

  1. Banerjee I, Raskin J, Arnoux JB, et al. Congenital hyperinsulinism in infancy and childhood: challenges, unmet needs and the perspective of patients and families. Orphanet J Rare Dis. 2022;17(1):61. doi:10.1186/s13023-022-02214-y ↩
  2. Thornton PS, De Leon DD, Empting S, et al. Dasiglucagon for the Treatment of Congenital Hyperinsulinism: A Randomized Phase 3 Trial in Infants and Children. J Clin Endocrinol Metab. 2024;109(4):1071–1079. doi:10.1210/clinem/dgad648 ↩
  3. De Leon DD, Banerjee I, Kummer S, et al. Dasiglucagon in Children With Congenital Hyperinsulinism Up to 1 Year of Age: Results From a Randomized Clinical Trial. J Clin Endocrinol Metab. 2025;110(8):e2674–e2681. doi:10.1210/clinem/dgae818 ↩
  4. Yau D, Laver TW, Dastamani A, et al. Using referral rates for genetic testing to determine the incidence of a rare disease: The minimal incidence of congenital hyperinsulinism in the UK is 1 in 28,389. PLoS One. 2020;15(2):e0228417. doi:10.1371/journal.pone.0228417 ↩
  5. De Franco E, Saint-Martin C, Brusgaard K, et al. Update of variants identified in the pancreatic β-cell K<sub>ATP</sub> channel genes KCNJ11 and ABCC8 in individuals with congenital hyperinsulinism and diabetes. Hum Mutat. 2020;41(5):884–905. doi:10.1002/humu.23995 ↩
  6. Rosenfeld E, Ganguly A, De León DD. Congenital hyperinsulinism disorders: Genetic and clinical characteristics. Am J Med Genet C Semin Med Genet. 2019;181(4):682–692. doi:10.1002/ajmg.c.31737 ↩
  7. Burns CM, Rutherford MA, Boardman JP, Cowan FM. Patterns of cerebral injury and neurodevelopmental outcomes after symptomatic neonatal hypoglycemia. Pediatrics. 2008;122(1):65–74. doi:10.1542/peds.2007-2822 ↩
  8. Thornton PS, Stanley CA, De Leon DD, et al. Recommendations from the Pediatric Endocrine Society for Evaluation and Management of Persistent Hypoglycemia in Neonates, Infants, and Children. J Pediatr. 2015;167(2):238–245. doi:10.1016/j.jpeds.2015.03.057 ↩
  9. Arnoux JB, Verkarre V, Saint-Martin C, et al. Congenital hyperinsulinism: current trends in diagnosis and therapy. Orphanet J Rare Dis. 2011;6:63. doi:10.1186/1750-1172-6-63 ↩
  10. De Cosio AP, Thornton P. Current and Emerging Agents for the Treatment of Hypoglycemia in Patients with Congenital Hyperinsulinism. Paediatr Drugs. 2019;21(3):123–136. doi:10.1007/s40272-019-00334-w ↩
  11. Adzick NS, De Leon DD, States LJ, et al. Surgical treatment of congenital hyperinsulinism: Results from 500 pancreatectomies in neonates and children. J Pediatr Surg. 2019;54(1):27–32. doi:10.1016/j.jpedsurg.2018.10.030 ↩
  12. Lord K, Radcliffe J, Gallagher PR, Adzick NS, Stanley CA, De León DD. High Risk of Diabetes and Neurobehavioral Deficits in Individuals With Surgically Treated Hyperinsulinism. J Clin Endocrinol Metab. 2015;100(11):4133–4139. doi:10.1210/jc.2015-2539 ↩
  13. Hövelmann U, Bysted BV, Mouritzen U, et al. Pharmacokinetic and Pharmacodynamic Characteristics of Dasiglucagon, a Novel Soluble and Stable Glucagon Analog. Diabetes Care. 2018;41(3):531–537. doi:10.2337/dc17-1402 ↩