This is a double-blind, placebo-controlled Phase 2 study to assess the efficacy, safety and tolerability of Glucagon RTU when administered to subjects with a history of bariatric surgery during episodes of post-postprandial hypoglycemia. Twelve eligible subjects will be randomly assigned to receive Glucagon RTU or placebo at the first of two clinical research center (CRC) visits, followed by the other treatment at the second CRC visit. Subjects will be randomly assigned to either Glucagon RTU or Placebo for the duration of a 12-week Outpatient Stage. A follow-up safety assessment visit will occur 14 to 28 days after a subject's last dose of study drug.

Inclusion Criteria:

1. Male or female

2. Aged 18 to 75 years of age, inclusive

3. Symptoms of hypoglycemia that developed after bariatric surgery (Roux-en-Y gastric bypass [RYGB] only) in the absence of antidiabetic medications

4. History of bariatric surgery (RYGB only), at least 6 months prior to screening

5. Whipple's triad

   1. Ability to both experience and recognize hypoglycemic awareness.
   2. Documented glucose levels < 54 mg/dL when experiencing symptoms suggestive of hypoglycemia
   3. Relief of hypoglycemia symptoms when the glucose is raised to normal

6. Diagnosis of post-bariatric hypoglycemia (PBH) by a physician, requiring intervention such as intake of oral carbohydrates. This diagnosis includes documentation of endogenous hyperinsulinism in the presence of low plasma glucose.

7. In subjects with medical history of diabetes, medical documentation of postoperative remission of diabetes mellitus (fasting glucose < 110 mg/dL), and HbA1c < 6% (or 42 mmol/mL) with all previous antidiabetic medication discontinued for at least 6 months before screening.

8. Body mass index (BMI) ≤ 40 kg/m2

9. Willingness to follow all study procedures, including attending all clinic visits and self-administering blinded study drug at home for 12 weeks

10. Understands the study procedures, alternative treatment available, and risks involved with the study, and he/she voluntarily agrees to participate by giving written informed consent

11. Women of childbearing potential must have a negative urine pregnancy test and agree to use contraception and refrain from breast-feeding during the study and for at least 15 days after participating in the study.

Exclusion Criteria:

1. Documented hypoglycemia occurring in the fasting state (> 12 hours fast) within 12 months of study entry
2. Hypoglycemic unawareness as evidenced by a Gold Scale score > 4 at screening
3. Early Dumping Syndrome
4. Known insulinoma or adrenal insufficiency
5. Active treatment with any insulin/insulin secretagogues, or other diabetes medications except for acarbose and glucagon-like peptide 1 (GLP-1) analogues
6. Chronic kidney disease Stage 4 or 5 or an estimated Glomerular Filtration Rate (eGFR) < 30 mL/min/1.73 m2 at screening
7. Hepatic disease, including serum alanine aminotransferase or aspartate aminotransferase ≥ 3 times the upper limit of normal (ULN); hepatic synthetic insufficiency as defined as serum albumin < 3.0 g/dL
8. Congestive heart failure, New York Heart Association Class III or IV
9. History of myocardial infarction, unstable angina, or revascularization within 6 months prior to screening.
10. History of a cerebrovascular accident within 6 months prior to screening or with major neurological deficits
11. Seizure disorder (other than with suspected or documented hypoglycemia).
12. Active malignancy, except for basal or squamous cell skin cancers
13. Personal or family history of pheochromocytoma or disorder with increased risk of pheochromocytoma (MEN 2, neurofibromatosis, or Von Hippel-Lindau disease)
14. Major surgical operation within 30 days prior to screening
15. Hematocrit ≤ 30%
16. Bleeding disorder, treatment with warfarin, or platelet count < 50,000 /mm3
17. Active alcohol abuse or substance abuse (per investigator assessment)
18. Current chronic administration of oral or parenteral corticosteroids, however topical, intraarticular, and inhaled corticosteroids are allowed
19. Use of an investigational drug within 15 days or 5 half-lives, whichever is longer, prior to screening
20. Member of a special vulnerable populations such as pregnant women, prisoners, institutionalized or incarcerated individuals, or others who may be considered vulnerable
21. Any other medical condition or finding that in the opinion of the investigator or sponsor, would compromise the safety of the subject or compromise the integrity of the study data

The sponsor, investigators/staff and subjects will be blinded to treatment assignment. Active study drug and placebo have the identical appearance (i.e., clear, colorless liquid), and both will be provided in identical vials with blinded labeling that does not reveal the contents of the vial.