Dasiglucagon (Zegalogue)
Dasiglucagon (ZP4207); supplied as dasiglucagon hydrochloride
FDA-approved (March 2021) glucagon receptor agonist analog for the treatment of severe hypoglycemia in pediatric (age 6+) and adult patients with diabetes, marketed as Zegalogue (PMID 34047955; NDA 214231).
Last updated: 2026-03-10
Safety Summary
In the two placebo-controlled adult Phase 3 trials (N=116 dasiglucagon, N=53 placebo), the most common adverse reactions within 12 hours of treatment were nausea (57% vs 4%), vomiting (25% vs 2%), headache (11% vs 4%), diarrhea (5% vs 0%), and injection site pain (2% vs 0%). Pediatric overall rates were nausea (65%), vomiting (50%), headache (10%), and injection site pain (5%). Other reported adverse reactions include hypertension, hypotension, bradycardia, presyncope, palpitations, and orthostatic intolerance. In the integrated safety analysis across 316 adults exposed to dasiglucagon, no serious adverse events, AEs leading to withdrawal, or deaths were reported. The safety profile was similar to that of reconstituted native glucagon (PMID 36692230). The immunogenicity trial (N=112, three weekly doses) found zero treatment-induced or treatment-boosted antidrug antibody responses and no injection site reactions with dasiglucagon (PMID 34252289). The QTc study showed no clinically relevant QTc prolongation at concentrations up to 5-fold higher than therapeutic levels (PMID 35464292). One case report documented necrolytic migratory erythema during prolonged continuous subcutaneous dasiglucagon infusion in a neonate with CHI, along with malnutrition and zinc deficiency, which resolved after drug discontinuation (PMID 40300042).
Known Side Effects
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Who Should NOT Use This
Contraindicated per FDA label. Dasiglucagon may stimulate the release of catecholamines from pheochromocytoma, causing a substantial increase in blood pressure.
Contraindicated per FDA label. Dasiglucagon may produce an initial increase in blood glucose but then stimulate exaggerated insulin release from an insulinoma, causing subsequent worsened hypoglycemia. Note: one case report described successful off-label use under IND for a suspected insulinoma refractory to conventional therapy (PMID 37454652).
Allergic reactions including generalized rash and in some cases anaphylactic shock with breathing difficulties and hypotension have been reported with glucagon products.
Hepatic stores of glycogen are necessary for dasiglucagon to produce an antihypoglycemic effect. Patients in states of starvation, adrenal insufficiency, or chronic hypoglycemia may have depleted glycogen stores and reduced efficacy. Treat with glucose instead.
Co-administration can cause a transient increase in pulse and blood pressure.
Indomethacin may blunt the glucose-raising effect of dasiglucagon or even produce hypoglycemia.
Dasiglucagon may increase the anticoagulant effect of warfarin. Monitor INR if administered to patients on warfarin.
Talk to Your Doctor
Before considering Dasiglucagon (Zegalogue), discuss it with your healthcare provider. Ask about potential interactions with your current medications, whether it is appropriate for your health conditions, and what monitoring may be needed.
Sources: [1-23]
Evidence Assessment
Tier 1: FDA-approved (March 2021, NDA 214231) for severe hypoglycemia rescue in diabetes patients aged 6 and older. Three Phase 3 RCTs (PMID 35239971, N=170; PMID 33934456, N=42; PMID 34169625, N=45) demonstrated superiority over placebo and comparability to native glucagon. Two independent meta-analyses confirmed these findings (PMID 37735694, PMID 36266088). An integrated safety and efficacy analysis pooled data from 316 adult exposures (PMID 36692230). Evidence for congenital hyperinsulinism, post-bariatric hypoglycemia, and low-dose non-severe hypoglycemia management is promising but remains investigational, so the tier is driven by the approved rescue indication. Note: FDA Drugs@FDA records list marketing status as 'Discontinued' for both formulations, though the NDA approval remains on record.
1Dasiglucagon-A Next-Generation Glucagon Analog for Rapid and Effective Treatment of Severe Hypoglycemia: Results of Phase 3 Randomized Double-Blind Clinical TrialNCT03378635PMID 35239971
Pieber TR et al. - Diabetes Care (2021) - Phase 3 RCT - N=170 (2:1:1 dasiglucagon:placebo:reconstituted glucagon)
Median time to PG recovery was 10 min for dasiglucagon vs 40 min for placebo (P < 0.001) vs 12 min for reconstituted glucagon. 99% of dasiglucagon-treated participants achieved recovery within 15 min. Most common AEs: nausea and vomiting.
Limitations: Controlled insulin-induced hypoglycemia setting, not real-world emergencies. Active comparator timing did not include glucagon reconstitution time. Manufacturer-sponsored (Zealand Pharma).
2Dasiglucagon, a next-generation ready-to-use glucagon analog, for treatment of severe hypoglycemia in children and adolescents with type 1 diabetes: Results of a phase 3, randomized controlled trialNCT03667053PMID 33934456
Battelino T et al. - Pediatric Diabetes (2021) - Phase 3 RCT - N=42 (2:1:1 dasiglucagon:placebo:reconstituted glucagon), ages 6-17
Median time to PG recovery: 10 min dasiglucagon vs 30 min placebo (P < 0.001). All dasiglucagon and glucagon participants recovered within 20 min vs 18% placebo. Safety similar to adult trials.
Limitations: Small sample size (N=42). Controlled insulin-induced hypoglycemia. Manufacturer-sponsored.
3Dasiglucagon, a next-generation glucagon analogue, for treatment of severe hypoglycaemia via an autoinjector device: Results of a phase 3, randomized, double-blind trialNCT03688711PMID 34169625
Bailey TS et al. - Diabetes, Obesity and Metabolism (2021) - Phase 3 RCT - N=45 (3:1 dasiglucagon:placebo)
Median time to recovery: 10 min dasiglucagon vs 35 min placebo (P < 0.001). 88% of dasiglucagon group recovered within 15 min vs 0% placebo (P < 0.01). Injection site (buttock vs deltoid) did not affect recovery time (P = 0.84). No serious AEs.
Limitations: Smaller confirmatory trial. Placebo-only comparator. Controlled setting. Manufacturer-sponsored.
4Pharmacokinetic and Pharmacodynamic Characteristics of Dasiglucagon, a Novel Soluble and Stable Glucagon AnalogNCT02916251PMID 29273578
Hovelmann U et al. - Diabetes Care (2018) - Phase 2 RCT (dose-ranging PK/PD) - N=58
Dasiglucagon demonstrated dose-dependent and rapid PG increase across 0.1-1.0 mg doses. Tmax approximately 35 min, half-life approximately 0.5 hours. PG increase of 20 mg/dL achieved in 9-14 min. Similar to GlucaGen but with longer-lasting and greater glucose effect. Nausea most frequent AE (44-56% both groups).
Limitations: Phase 2 dose-finding. Single-center. Not powered for definitive efficacy. Manufacturer-sponsored.
5Low doses of dasiglucagon consistently increase plasma glucose levels from hypoglycaemia and euglycaemia in people with type 1 diabetes mellitusPMID 30350477
Hovelmann U et al. - Diabetes, Obesity and Metabolism (2019) - Phase 2 RCT (dose-ranging) - N=17
Low doses (0.03-0.2 mg) dasiglucagon produced dose-dependent and rapid PG increases under both euglycemic and hypoglycemic conditions. Mean PG increases of 2.2-4.4 mmol/L from euglycemia and 1.3-5.2 mmol/L from hypoglycemia at 30 min. Supports use in dual-hormone artificial pancreas systems.
Limitations: Small sample (N=17). Single-center. Manufacturer-sponsored.
6Integrated safety and efficacy analysis of dasiglucagon for the treatment of severe hypoglycaemia in individuals with type 1 diabetesPMID 36692230
Heller S et al. - Diabetes, Obesity and Metabolism (2023) - Integrated analysis / pooled analysis - Placebo-controlled pool: N=116 dasiglucagon; Broad pool: 6 trials, 316 adults total
No serious AEs, AEs leading to withdrawal, or deaths reported. Most common causally related AEs: nausea (56.5%), vomiting (24.6%). Median recovery time: 10 min dasiglucagon vs 12 min reconstituted glucagon vs 40 min placebo (P < 0.0001). Recovery time consistent across all demographic subgroups.
Limitations: Post-hoc pooled analysis. All source data from manufacturer-sponsored trials.
7Immunogenicity of the Novel Glucagon Analogue Dasiglucagon: Results of a Dedicated Immunogenicity Trial in Type 1 DiabetesNCT03216226PMID 34252289
Pieber TR et al. - Diabetes Technology and Therapeutics (2021) - Phase 3 RCT (immunogenicity) - N=112 (1:1 dasiglucagon:GlucaGen), 3 weekly doses, 15-week follow-up
Overall antidrug antibody (ADA) incidence was zero. No subject demonstrated any treatment-induced or treatment-boosted ADA response at any time point. No injection site reactions with dasiglucagon. No unexpected safety findings.
Limitations: Only 3 doses administered (appropriate for rescue use but does not assess long-term immunogenicity). Manufacturer-sponsored.
8Dasiglucagon Effects on QTc in Healthy Volunteers: A Randomized, Placebo-Controlled, Dose-Escalation, Double-Blind StudyNCT03735225PMID 35464292
Tehranchi R et al. - Current Therapeutic Research (2022) - Phase 1 RCT (cardiac safety) - N=60 healthy volunteers
No clinically relevant QTc prolongation at concentrations up to approximately 30,000 pmol/L (5-fold higher than peak therapeutic). Emax model: maximum QTcF effect 3.6 ms (90% CI: 1.23-5.95 ms), below 10 ms regulatory threshold. No clinically relevant effects on heart rate, PR interval, or QRS duration.
Limitations: Single-center. Healthy volunteers, not diabetes patients. Manufacturer-sponsored.
9Dasiglucagon for the Treatment of Insulin-induced Hypoglycemia in Patients with Type 1 Diabetes Mellitus: A Meta-analysisPMID 37735694
Maji S et al. - Balkan Medical Journal (2023) - Meta-analysis - 5 RCTs included
Time to recovery earlier with dasiglucagon vs placebo (MD: -24.73 min; 95% CI: -30.94 to -18.52; P < 0.00001) and vs oral glucose (MD: -15.00 min; 95% CI: -20.33 to -9.67; P < 0.00001). Difference between dasiglucagon and native glucagon was not statistically significant (MD: -0.76 min; 95% CI: -2.19 to 0.66; P = 0.29).
Limitations: Only 5 trials available. All source trials manufacturer-sponsored. Heterogeneity in dosing protocols.
10Clinical efficacy and safety of dasiglucagon in severe hypoglycemia associated with patients of type 1 diabetes mellitus: a systematic review and meta-analysisPMID 36266088
Dholariya S et al. - Expert Review of Clinical Pharmacology (2023) - Systematic review and meta-analysis - 5 RCTs, 347 patients total
Dasiglucagon significantly reduced recovery time vs glucagon (PMD: 1.08%, 95% CI: 1.96 to 0.21, P = 0.02) and vs placebo (PMD: -23.30%, 95% CI: -23.97 to -22.63, P < 0.00001). Safety outcomes comparable to native glucagon.
Limitations: Small total sample. All source trials manufacturer-sponsored.
11Dasiglucagon for the Treatment of Congenital Hyperinsulinism: A Randomized Phase 3 Trial in Infants and ChildrenNCT04172441PMID 37930757
Thornton PS et al. - Journal of Clinical Endocrinology and Metabolism (2024) - Phase 3 RCT (open-label with randomized period) - N=32 (ages 0.6-10.9 years)
Primary endpoint (SMPG-detected hypoglycemia) not significantly different between groups (P = 0.50). Post hoc analysis showed 43% reduction in CGM-detected hypoglycemia (<3.9 mmol/L) vs SoC alone (event rate ratio: 0.57, 95% CI: 0.39-0.83, P = 0.003). 37-61% reductions in all other CGM measures. Skin and GI events more frequent with dasiglucagon.
Limitations: Primary endpoint not met. Key positive results from post hoc analysis. Open-label design. Small sample. Not yet approved for CHI. Manufacturer-sponsored.
12Dasiglucagon in Children With Congenital Hyperinsulinism Up to 1 Year of Age: Results From a Randomized Clinical TrialPMID 39584500
De Leon DD et al. - Journal of Clinical Endocrinology and Metabolism (2025) - Phase 2/3 RCT (crossover, double-blind) - N=12 infants (aged 7 days to 12 months)
IV glucose infusion rate significantly reduced with dasiglucagon vs placebo (LS mean 4.3 vs 9.5 mg/kg/min, P = 0.004). Most frequent AEs: GI, dermatological, and metabolic/nutritional disorders.
Limitations: Very small sample (N=12). Short treatment periods (48h crossover, 21 days open-label). Manufacturer-sponsored.
13Dasiglucagon Treatment for Postprandial Hypoglycemia After Gastric Bypass: A Randomized, Double-Blind, Placebo-Controlled TrialNCT04836273PMID 37819999
Nielsen CK et al. - Diabetes Care (2023) - Phase 2 RCT (crossover, double-blind) - N=24 (23 women, RYGB-operated)
Dasiglucagon 120 mcg reduced time in level 1 hypoglycemia by 33% (-1.2 percentage points, P = 0.002) and level 2 hypoglycemia by 54% (-0.4 percentage points, P < 0.0001) vs placebo over 4 weeks. Hypoglycemia corrected within 15 min in 97.3% vs 29.1% of self-administrations. Generally well tolerated.
Limitations: Small sample. 4-week duration. Mostly women. Investigator-initiated with Zealand Pharma drug and financial support.
14Dasiglucagon Effectively Mitigates Postbariatric Postprandial Hypoglycemia: A Randomized, Double-Blind, Placebo-Controlled, Crossover TrialNCT03984370PMID 35320361
Nielsen CK et al. - Diabetes Care (2022) - Phase 2 RCT (crossover) - N=10 (RYGB-operated with CGM-verified PBH)
Both 80 and 200 mcg dasiglucagon raised nadir PG vs placebo (3.9 and 4.5 vs 3.0 mmol/L, P = 0.002 and P = 0.0002) and reduced time in hypoglycemia by 70 min (P = 0.030 and P = 0.008).
Limitations: Very small sample (N=10). Single meal test day. Proof-of-concept. Investigator-initiated with Zealand Pharma support.
15Low-Dose Dasiglucagon Versus Oral Glucose for Prevention of Insulin-Induced Hypoglycemia in People With Type 1 Diabetes: A Phase 2, Randomized, Three-Arm Crossover StudyNCT04449692PMID 35475907
Laugesen C et al. - Diabetes Care (2022) - Phase 2 RCT (crossover) - N=20 adults with T1DM
Low-dose dasiglucagon (80-120 mcg) produced faster glucose increase than oral glucose (median time to 20 mg/dL increase: 15 vs 30 min, P = 0.006 for D80 and P = 0.003 for D120 vs oral). D120 significantly reduced hypoglycemia incidence vs oral glucose (P = 0.034).
Limitations: Small sample (N=20). Off-label doses. Controlled insulin-bolus model. Investigator-initiated with Zealand Pharma support.
16Pen-administered low-dose dasiglucagon vs usual care for prevention and treatment of non-severe hypoglycaemia in people with type 1 diabetes during free-living conditionsNCT04764968PMID 37037948
Laugesen C et al. - Diabetologia (2023) - Phase 2 RCT (crossover, open-label, 2-week periods) - N=24 adults with pump-treated T1DM
Recovery rate from hypoglycemia was 44% faster with dasiglucagon vs usual care. Total daily carbohydrate intake reduced by 11% (P < 0.05). 96% of participants reported they would likely include dasiglucagon in future management. Safe and well tolerated.
Limitations: Open-label design (potential bias). Small sample. 2-week periods. Investigator-initiated with Zealand Pharma support.
17A Comparative Study of Dasiglucagon Ready-to-Use Autoinjector and Glucagon Emergency Kit During Rescue from Simulated Severe HypoglycemiaPMID 34809479
Bailey NC et al. - Diabetes Technology and Therapeutics (2022) - Device handling study (crossover) - N=54 (18 caregiver pairs, 18 bystanders)
94% of trained caregivers successfully administered dasiglucagon autoinjector within 15 min vs 56% for GEK (P < 0.05). Time to successful completion significantly faster for autoinjector (P < 0.005). 94% preferred autoinjector over GEK (P < 0.001).
Limitations: Simulated emergency using manikins, not actual hypoglycemic events. Manufacturer-sponsored.
18Systematic Literature Review and Indirect Treatment Comparison of Three Ready-to-Use Glucagon Treatments for Severe HypoglycemiaPMID 37707700
Gimenez M et al. - Diabetes Therapy (2023) - Systematic review and indirect treatment comparison - 10 clinical trials (4 Baqsimi, 3 Gvoke, 3 Zegalogue)
All three ready-to-use glucagon treatments achieved >98% treatment success. Baqsimi: lower max glucose (168 mg/dL) vs Gvoke (220 mg/dL) and Zegalogue (190 mg/dL). Trend toward fewer TEAEs with Baqsimi but not statistically significant.
Limitations: Indirect comparison (not head-to-head). Inherent limitations of network meta-analysis. Funded by Eli Lilly (Baqsimi manufacturer).
19Dasiglucagon demonstrates reduced costs in the treatment of severe hypoglycemia in a budget impact modelPMID 35332789
Hinahara J et al. - Journal of Managed Care and Specialty Pharmacy (2022) - Budget impact model - Hypothetical 1 million-covered lives commercial health plan
Total SHE treatment costs with dasiglucagon: $13.4M vs $16.7M injectable glucagon, $20.7M nasal glucagon, $35.3M reconstituted glucagon, $43.8M untreated. NNT with dasiglucagon to avoid 1 hospitalization: 6.
Limitations: Model-based, not real-world outcomes. Funded by Zealand Pharma. Authors include Zealand Pharma employees.
20Necrolytic migratory erythema following prolonged continuous subcutaneous dasiglucagon administration: a rare dermatologic adverse eventPMID 40300042
Weschle L et al. - Endocrinology, Diabetes and Metabolism Case Reports (2025) - Case report - N=1 (neonate with CHI)
Prolonged continuous SC dasiglucagon in a neonate with CHI led to necrolytic migratory erythema, severe malnutrition, zinc and amino acid deficiencies, and sepsis. Skin and nutritional status improved after dasiglucagon discontinuation. Patient ultimately required subtotal pancreatectomy.
Limitations: Single case report. NME is a known complication of hyperglucagonemia. Off-label use in neonate with prolonged infusion.
21Hypoglycemia and Alzheimer Disease Risk: The Possible Role of DasiglucagonPMID 38977507
Ali NH et al. - Cellular and Molecular Neurobiology (2024) - Narrative review (hypothesis-generating) - N/A (review article)
Hypothesizes that recurrent hypoglycemia increases AD risk via endothelial dysfunction, thrombosis, tau hyperphosphorylation, and amyloid-beta accumulation. Proposes dasiglucagon could reduce AD neuropathology by preventing hypoglycemia. No clinical evidence presented.
Limitations: Entirely theoretical/hypothesis-generating. No clinical or preclinical data for dasiglucagon in AD. Narrative review, not systematic.
22Novel Use of Dasiglucagon, a Soluble Glucagon Analog, for the Treatment of Hyperinsulinemic Hypoglycemia Secondary to Suspected Insulinoma: A Case ReportPMID 37454652
Reynolds D et al. - Hormone Research in Paediatrics (2024) - Case report - N=1 (17-year-old male)
Dasiglucagon used under single-patient IND for hyperinsulinemic hypoglycemia from suspected insulinoma refractory to conventional therapy. Patient tolerated medication and achieved appropriate glycemic control.
Limitations: Single case report. Off-label use under IND. Despite FDA contraindication for insulinoma.
23Glucose-Driven Droplet Formation in Complexes of a Supramolecular Peptide and Therapeutic ProteinPMID 38465595
Yu S et al. - Journal of the American Chemical Society (2024) - Preclinical / materials science - In vitro and mouse model
Developed a glucose-responsive supramolecular droplet system that releases dasiglucagon in low-glucose environments. Demonstrated functional hypoglycemic rescue in a mouse model of insulin overdose.
Limitations: Preclinical/proof-of-concept only. Mouse model. Early-stage materials science. No human data.