The aim of this study is investigating the effect of a novel glucagon analogue administration in gastric bypass operated individuals, who are reactive hypoglycemic.

The Roux-En-Y gastric bypass (RYGB) has major health-promoting effects - reversing type-2-diabetes, improving dyslipidemia and inducing robust weight loss. However, several RYGB-individuals, post surgery, suffers from dumping syndrome and postprandial hyperinsulinemic hypoglycemia (PHH) due to the anatomical rearrangement of the gastro-intestinal system. Dasiglugaon (also known as (ZP4207) has shown great pharmacokinetic- and dynamic effects, compared to other glucagon analogues on the market, when administrated to hypoglycemic type-1-diabetics.

Therefore we aim to examine the effects of two different doses of dasiglucagon on the postprandial nadir plasma glucose concentration in RYGB-operated individuals suffering from PHH by use of a mixed meal test (MMT).

The study is designed as a double-blinded, randomised, 3-period, 3-treatment, crossover study comprising 3 separate treatment days in which participants will undergo an MMT along with one of the following double-blinded interventions:

1. Subcutaneous (sc) placebo (saline) injection
2. Sc injection with 80 μg dasiglucagon
3. Sc injection with 200 μg dasiglucagon

Inclusion Criteria:

• Documented postprandial hypoglycaemia (<3.9 mmol/l) by 6-day CGM or during a MMT
• Documented plasma glucose concentration excursions >5.0 mmol/l by 6-day CGM or a MMT
• Haemoglobin levels for women >7.3 mmol/l and for men >8.3 mmol/l
• Ferritin >10 μg/l
• Cobalamin >150 pmol/l
• Fasting plasma glucose concentration within the range of 4.0-6.0 mmol/l CKN-DASI-RYGB protocol version 1.0 6
• Normal electrocardiogram (ECG)
• Negative urine human chorionic gonadotropin (hCG) (for fertile women)

Exclusion Criteria:

• Treatment with medication(s) affecting insulin secretion or any antidiabetic drugs
• Treatment with antipsychotics
• Current participation in another clinical trial with administration of investigational drug.
• Previous exposure to dasiglucagon (otherwise known as ZP4207)
• History of liver disease that is expected to interfere with the anti-hypoglycaemic action of glucagon (e.g. liver failure or cirrhosis).
• Pregnancy
• Breastfeeding
• Any factors that, in the opinion of the site principal investigator or clinical protocol chair, would interfere with the safe completion of the study, including medical conditions that may require hospitalization during the trial or allergy to the ingredients in the study drug.