What Is Dasiglucagon?

1. How is dasiglucagon different from regular glucagon?

Dasiglucagon has the same length as human glucagon, 29 amino acids, “but with seven amino acid substitutions compared with endogenous glucagon to increase the physical and chemical stability in aqueous media,” according to the adult Phase 3 paper. It keeps its selectivity for the glucagon receptor, so it acts the same way once injected (Pieber et al., 2021).

The practical difference is the package. Zegalogue’s label describes a clear, colorless, preservative-free solution in a single-dose autoinjector or prefilled syringe containing 0.6 mg. There is nothing to reconstitute. The drug can be stored in a refrigerator, or at room temperature for up to 12 months, after which it must be discarded (Zegalogue label).

Dasiglucagon is one of several modern glucagon products, alongside nasal glucagon and other ready-to-use injections. It does not raise blood sugar by a different mechanism. It still needs glycogen stored in the liver to work, which matters in section 6.

2. How does dasiglucagon work in the body?

The label states that dasiglucagon “increases blood glucose concentration by activating hepatic glucagon receptors, thereby stimulating glycogen breakdown and release of glucose from the liver” (Zegalogue label). Its pharmacology, from the same label:

The short half-life is deliberate. A rescue drug needs to act within minutes and then fade, leaving food to restore the liver’s glycogen. That is why the label tells caregivers to give oral carbohydrates once the person responds.

3. What did the clinical trials show?

Zegalogue’s approval rests on three randomized, double-blind trials in people with type 1 diabetes. In each, researchers lowered blood sugar on purpose with intravenous insulin in a monitored setting, then gave dasiglucagon, placebo or, in two trials, standard reconstituted glucagon. The main outcome was the time until glucose rose by at least 20 mg/dL without rescue IV glucose (Zegalogue label).

In the adult trial, glucose recovered within 15 minutes in 99% of the dasiglucagon group, against 2% on placebo and 95% on glucagon (Pieber et al., 2021). In the pediatric trial, every child on dasiglucagon or glucagon recovered within 20 minutes, against 2 of 11 on placebo. The authors note that the glucagon time did not include the minutes needed to mix the powder (Battelino et al., 2021).

A 2023 meta-analysis of five randomized trials found dasiglucagon faster than placebo or oral glucose but not statistically faster than conventional glucagon, a mean difference of −0.76 minutes (meta-analysis, 2023). In plain terms, its advantage is readiness, not raw speed once injected.

The June 2026 label change

The original label covered people aged 6 and older. Zealand Pharma ran a separate open-label trial in children under 6 with type 1 diabetes (NCT05378672), and the FDA approved an efficacy supplement on June 18, 2026 (openFDA record). The revised label now defines the population by weight: adults and children with diabetes “who weigh at least 20 kg.” It says safety and effectiveness have not been established below 20 kg, and that the under-6 trial showed a safety profile similar to older patients (Zegalogue label).

4. What are the side effects and warnings?

Side effects are those of glucagon itself, mainly nausea and vomiting. The label’s placebo-controlled data, within 12 hours of a dose (Zegalogue label):

Teenagers had the highest rates: 92% nausea and 67% vomiting in the 12 to 17 group. Other reactions within 12 hours included high or low blood pressure, slow heart rate, near-fainting and palpitations.

The label’s key safety points:

• Contraindications: pheochromocytoma, because glucagon can release catecholamines from the tumor and sharply raise blood pressure; and insulinoma, because it can trigger a burst of insulin that causes later hypoglycemia.
• Allergic reactions have been reported with glucagon products, including rare anaphylaxis.
• Low liver glycogen: it may not work in starvation, adrenal insufficiency or chronic hypoglycemia.
• Interactions: beta-blockers may cause a brief rise in pulse and blood pressure; with indomethacin, dasiglucagon may fail to raise glucose or may even cause hypoglycemia; it may increase the effect of warfarin.
• Antibodies: 4 of 506 people treated in studies developed anti-drug antibodies (Zegalogue label). A dedicated trial of three weekly doses found no treatment-induced antibodies at all (immunogenicity trial, 2021).

5. What is the congenital hyperinsulinism program?

Congenital hyperinsulinism (CHI) is a rare disease, usually genetic, in which the pancreas releases insulin even when blood sugar is low. Babies can have repeated, severe hypoglycemia that risks lasting brain injury. Zealand Pharma notes that diazoxide is the only approved medical treatment, and that more than half of patients do not respond adequately to current options. Severe cases may need surgical removal of most of the pancreas, which leaves many children with diabetes later (Zealand regulatory update, October 2024; Phase 3 infant trial).

Because dasiglucagon is stable in liquid, it can run continuously under the skin from a wearable pump, which natural glucagon cannot do for long. Zealand developed the pump system with DEKA Research & Development (priority review announcement). Both the FDA and the European Commission have granted it orphan drug designation for CHI (Zealand Q3 2025 report).

The two Phase 3 trials

Infants (trial 17103, NCT04172441). Twelve babies aged 7 days to 12 months who depended on IV glucose received dasiglucagon or placebo for 48 hours each in a crossover design. Over the last 12 hours, the IV glucose infusion rate needed to keep blood sugar safe was 4.3 mg/kg/min on dasiglucagon versus 9.5 mg/kg/min on placebo (P = .004). In the 21-day open-label part, 10 of 12 infants were off IV glucose by the end of week 2, and 7 stayed off it at study completion without needing pancreatectomy. Median time to weaning off IV glucose was 5.8 days. One participant had serious adverse events during part 2, and none stopped treatment because of side effects (JCEM 2025 infant trial).

Older children (trial 17109, NCT03777176). Thirty-two children aged 0.6 to 10.9 years with persistent hypoglycemia despite standard care were randomized to standard care with or without a dasiglucagon infusion of 10 to 70 µg per hour for four weeks. The primary endpoint, hypoglycemia counted by finger-stick tests, was not met (rate ratio 0.85, P = .50). A post hoc analysis of blinded continuous glucose monitoring (CGM) found 43% fewer hypoglycemia episodes on dasiglucagon (JCEM 2024 trial). That split is why the FDA later asked for more CGM analyses before considering use beyond three weeks.

A long-term extension enrolled children from both trials and is listed as completed (NCT03941236). A 2025 case report described necrolytic migratory erythema, a skin condition linked to high glucagon levels, plus malnutrition, zinc and amino acid deficiencies and sepsis in a newborn on prolonged infusion; the problems improved after dasiglucagon was stopped (case report, 2025). One case cannot set a rate, but it shows why long-term pump use needs close monitoring.

FDA history

As of November 8, 2026, dasiglucagon is not approved for congenital hyperinsulinism in the US, and I found no public confirmation that the resubmission has been filed. A complete response letter is the FDA’s formal “not yet” when an application cannot be approved in its current form.

6. Why does dasiglucagon matter for people on GLP-1 drugs?

The Ozempic label explains that semaglutide stimulates insulin secretion and lowers glucagon secretion “both in a glucose-dependent manner,” meaning the effect weakens as blood sugar falls. The risk changes when it is combined with drugs that push insulin regardless of glucose. The label includes a specific warning: patients taking it with an insulin secretagogue such as a sulfonylurea, or with insulin, “may have an increased risk of hypoglycemia, including severe hypoglycemia,” and lowering the dose of those drugs may reduce the risk (Ozempic label).

The trial numbers in that label show the size of the effect:

Source: Ozempic label. Severe hypoglycemia means the person needed help from someone else to recover, exactly the situation a rescue drug like Zegalogue is meant for. The Ozempic figures are the ones quoted here; other GLP-1 drugs such as tirzepatide have their own labels and trial numbers.

Three practical points follow from the Zegalogue label:

1. Someone else has to give it. Because severe hypoglycemia “requires the help of others to recover,” the label tells patients to show the people around them where it is and how it works (Zegalogue label). A ready-to-use device removes the mixing step that trips up untrained helpers.
2. It needs stored glycogen. The label warns that glucagon products may not work in “states of starvation.” People eating very little on a GLP-1 drug are not necessarily in that state, but very low intake is worth mentioning to the prescriber who decides on a rescue plan.
3. Nausea is common on both drugs. Dasiglucagon caused nausea in 57% of adults. Someone already prone to GLP-1 nausea may vomit after a rescue dose, which makes the follow-up oral carbohydrates harder to keep down and is one more reason the label says to call emergency services.

For the insulin side of the picture, see what is insulin. For dose reductions of insulin or sulfonylureas when starting a GLP-1 drug, the prescriber and label are the authority; this page does not give that advice.

Post-bariatric hypoglycemia

Dasiglucagon has also been studied for low blood sugar after gastric bypass surgery, which is driven partly by exaggerated GLP-1 and insulin release after meals. A 2025 systematic review found it “showed efficacy as a rescue agent,” while rating the overall evidence for drug treatments in this condition as very low certainty (post-bariatric hypoglycemia review). This use is not approved.

7. How does dasiglucagon fit with other peptide drugs?

Dasiglucagon is one of several engineered gut and pancreatic hormones on this site, but its job is the opposite of most of them. GLP-1, GIP and amylin drugs lower glucose or appetite. Dasiglucagon raises glucose quickly in an emergency. Long-acting glucagon receptor agonists used in obesity drugs, such as survodutide, are different molecules designed for weekly dosing and steady effects on energy use and liver fat, not rescue.

Its stability has also made it useful in research devices. In a home-use study of the bihormonal iLet bionic pancreas, dasiglucagon was the glucagon component paired with insulin in adults with type 1 diabetes (El-Khatib et al., 2021). No such dual-hormone system is approved.

Zealand Pharma, which created dasiglucagon, licensed Zegalogue’s worldwide commercial rights to Novo Nordisk in September 2022 for an upfront payment of DKK 25 million plus milestones and royalties, while keeping rights to its other dasiglucagon programs, including CHI (license agreement report). The current label lists Novo Nordisk as the contact for adverse event reports. Zealand’s other peptides include glepaglutide, a long-acting GLP-2 analog for short bowel syndrome.

For a personal record, a rescue dose is worth logging as an event: date, time, product, who gave it, and what happened next. That record is useful at the next appointment, when the prescriber reviews whether insulin or sulfonylurea doses need to change. How GLP-1 tracking works covers what to record alongside a weekly GLP-1 injection.

8. Dasiglucagon FAQ

• Is dasiglucagon the same as glucagon?

  It is a modified version. Like natural glucagon it has 29 amino acids and acts on the glucagon receptor in the liver, but seven amino acids are swapped to stop it from clumping in water. That stability is why Zegalogue can be sold as a ready-to-use liquid, while older glucagon kits had to be mixed from powder just before injection.

• What is Zegalogue approved for?

  Zegalogue is approved in the US to treat severe hypoglycemia in adults and pediatric patients with diabetes who weigh at least 20 kg. The original 2021 approval covered people aged 6 and older; the June 2026 label revision switched to the weight-based criterion. It is not approved for congenital hyperinsulinism.

• How fast does dasiglucagon work?

  In the adult Phase 3 trial, median time to plasma glucose recovery was 10 minutes, against 40 minutes on placebo and 12 minutes with reconstituted glucagon. All but one participant on dasiglucagon recovered within 15 minutes. Recovery was defined as a rise of at least 20 mg/dL without rescue glucose.

• What is the labeled dose of Zegalogue?

  The label dose is 0.6 mg injected under the skin. If there is no response after 15 minutes, a second 0.6 mg dose from a new device may be given while waiting for emergency help. The label says to call for emergency assistance right after the injection and give oral carbohydrates once the person responds.

• What are the side effects of dasiglucagon?

  In adult placebo-controlled trials, within 12 hours of a dose, nausea occurred in 57% (4% on placebo), vomiting in 25% (2%), headache in 11% (4%) and diarrhea in 5% (0%). In children aged 6 to 17, nausea occurred in 65% and vomiting in 50%. It is contraindicated with pheochromocytoma and insulinoma.

• Do people on Ozempic or Mounjaro need glucagon?

  That is a decision for the prescriber. The Ozempic label warns that combining semaglutide with insulin or a sulfonylurea increases the risk of hypoglycemia, including severe hypoglycemia, and suggests lowering the dose of those drugs. People in that situation are the ones for whom a glucagon rescue product is usually discussed.

• Is dasiglucagon approved for congenital hyperinsulinism?

  No. The FDA issued two complete response letters, the second on October 9, 2024, both tied to a third-party manufacturing facility rather than the clinical data. Zealand Pharma said in its August 13, 2026 report that it expected to resubmit the application in the second half of 2026.

• Does dasiglucagon work if someone has not been eating?

  Possibly not well. The label says dasiglucagon works only if the liver has enough stored glycogen, and that people in states of starvation, with adrenal insufficiency or with chronic hypoglycemia may not respond and should be treated with glucose instead.

9. Sources