NCT03255629

Closed-Loop Glucagon Pump for Treatment of Post-Bariatric Hypoglycemia

Completed Phase 1, PHASE2 Results posted Last updated 6 September 2022

What this trial tests

Phase 1, PHASE2 trial testing glucagon in Post-bariatric Hypoglycemia in 18 participants. Completed in 22 August 2018.

Timeline

19 September 2017

Primary endpoint
22 August 2018

22 August 2018

Quick facts

Lead sponsor	Joslin Diabetes Center
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	quadruple
Primary purpose	prevention
Enrollment	18
Start date	19 September 2017
Primary completion	22 August 2018
Estimated completion	22 August 2018
Sites	1 location across United States

Drugs / interventions tested

• glucagon (GLUCAGON) — full drug profile →
• Closed loop glucagon pump

Conditions studied

• Post-bariatric Hypoglycemia — all drugs for Post-bariatric Hypoglycemia →

Sponsor

Joslin Diabetes Center — full company profile →

Who can join

Adults 18 to 65, any sex, with Post-bariatric Hypoglycemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Meal-provoked Hypoglycemia, Defined as Sensor Glucose <65 mg/dL Primary · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

A primary endpoint for this study is the prevention of meal provoked hypoglycemia, defined as sensor glucose levels below \<65 mg/dl, comparing study drug to control.

Group	Value	95% CI
Study Drug (Glucagon) Phase	1
Placebo / Control Phase	5

Number of Participants With Meal-provoked Hypoglycemia, Defined as Plasma Glucose <65 mg/dL Primary · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

A primary endpoint for this study is prevention of meal provoked hypoglycemia, defined as plasma glucose levels below \<65 mg/dl, comparing study drug to control

Group	Value	95% CI
Study Drug (Glucagon) Phase	1
Placebo / Control Phase	4

Number of Participants With Meal-provoked Hypoglycemia, Defined as Sensor Glucose <60 mg/dL Secondary · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

Prevention of meal / provoked hypoglycemia, defined as sensor glucose levels below \<60 mg/dl, comparing vehicle to control

Group	Value	95% CI
Study Drug (Glucagon) Phase	1
Placebo / Control Phase	3

Number of Participants With Rebound Hyperglycemia (Defined as Glucose Levels Above 180 mg/dl). Secondary · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge will be conducted within two weeks of the first.

Compare outcomes for glucagon versus vehicle infusions for prevention of rebound hyperglycemia (defined as glucose levels above 180 mg/dl).

Group	Value	95% CI
Study Drug (Glucagon) Phase	0
Placebo / Control Phase	0

Number of Participants With Hypoglycemia Rescue Administered Secondary · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

Protocol-specified rescue delivery of IV glucose was performed if plasma glucose \<55 mg/dL and/or significant neuroglycopenia developed.

Group	Value	95% CI
Study Drug (Glucagon) Phase	0
Placebo / Control Phase	7

Number of Participants With Meal-provoked Hypoglycemia, Defined as Plasma Glucose <60 mg/dL Secondary · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

Prevention of meal / provoked hypoglycemia, defined as plasma glucose levels below \<60 mg/dl, comparing vehicle to control

Group	Value	95% CI
Study Drug (Glucagon) Phase	0
Placebo / Control Phase	3

Number of Participants With Meal-provoked Hypoglycemia, Defined as Plasma Glucose <55 mg/dL Secondary · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

Prevention of meal / provoked hypoglycemia, defined as plasma glucose levels below \<55 mg/dl, comparing vehicle to control

Group	Value	95% CI
Study Drug (Glucagon) Phase	0
Placebo / Control Phase	5

Number of Participants With Meal-provoked Hypoglycemia, Defined as Sensor Glucose <55 mg/dL Secondary · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

Prevention of meal / provoked hypoglycemia, defined as sensor glucose levels below \<55 mg/dl, comparing vehicle to control

Group	Value	95% CI
Study Drug (Glucagon) Phase	0
Placebo / Control Phase	0

Percent Time Plasma Glucose in Range After the Final Dose of Study Drug or Vehicle, Which Was Either 1 or 2 Doses Depending on Patient Response Secondary · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

Compare outcomes for glucagon versus vehicle infusions for percent time plasma glucose in range (180-65mg/dL) after the final dose, which was either 1 or 2 doses depending on patient response

Group	Value	95% CI
Study Drug (Glucagon) Phase	0.852	± 0.082
Placebo / Control Phase	0.645	± 0.074

Percent Time Sensor Glucose in Range After Drug Delivery After the Final Dose of Study Drug or Vehicle, Which Was Either 1 or 2 Doses Depending on Patient Response Secondary · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

Compare outcomes for glucagon versus vehicle infusions for percent time sensor glucose in range (180-65mg/dL) after the final dose, which was either 1 or 2 doses depending on patient response

Group	Value	95% CI
Study Drug (Glucagon) Phase	0.987	± 0.013
Placebo / Control Phase	0.815	± 0.077

Meal Provoked Nadir Plasma Glucose Secondary · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

Nadir plasma glucose (mg/dl) during meal testing, comparing vehicle to control

Group	Value	95% CI
Study Drug (Glucagon) Phase	67.4	± 2.70
Placebo / Control Phase	58.5	± 1.87

Meal Provoked Nadir Sensor Glucose Secondary · Measured following 2 challenges: 1 with glucagon and 1 with vehicle. The second challenge was conducted within two weeks of the first.

Nadir sensor glucose (mg/dl) during meal testing, comparing vehicle to control

Group	Value	95% CI
Study Drug (Glucagon) Phase	72.7	± 2.21
Placebo / Control Phase	65.3	± 1.85

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse event data were collected over the the duration of each individuals participation, a 2 to 3 week period of time, encompassing the time of enrollment, to the completion of visit 5.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment Arm and Control Arm (Randomized, Double-Blind, Placebo-Controlled Crossover Design)

Serious: 1/18 (6%)

Deaths: 0/18

Serious adverse events (1 terms)

Reaction	System	Treatment Arm and Control …
Hypokalemia	Metabolism and nutrition disorders	—

Other adverse events (80 terms — click to expand)

Reaction	System	Treatment Arm and Control …
Hypoglycemia during study (MMTT)	Endocrine disorders	—
Buring pain at pump site after alarm (glucagon visit)	General disorders	—
Nausea after intake of mixed meal (prior to glucagon OR placebo)	Gastrointestinal disorders	—
Tiredness after intake of mixed meal (prior to study drug OR placebo)	General disorders	—
Erythema at pump infusion site (glucagon visit)	Skin and subcutaneous tissue disorders	—
Burning pain / pricking at pump site after alarm (placebo visit)	General disorders	—
Erythema at pump infusion site (placebo visit)	Skin and subcutaneous tissue disorders	—
Headache after intake of mixed meal (prior to glucagon OR placebo)	General disorders	—
Palpitations after intake of mixed meal (prior to study drug OR placebo)	Cardiac disorders	—
Feeling hot / warm after intake of mixed meal (prior to study drug or placebo)	General disorders	—
Edema at pump infusion site (glucagon visit)	Skin and subcutaneous tissue disorders	—
Edema at pump infusion site (placebo visit)	Skin and subcutaneous tissue disorders	—
Tiredness day after study visit (glucagon visit)	General disorders	—
Feeling cold / chills after intake of mixed meal (prior to study drug OR placebo)	General disorders	—
Feeling hot after alarm (placebo visit)	General disorders	—
Tiredness day after study visit (placebo visit)	Gastrointestinal disorders	—
Headache prior to start of MMTT	General disorders	—
Emesis after intake of mixed meal (prior to study drug OR placebo)	Gastrointestinal disorders	—
Stomach ache / cramping after intake of mixed meal (prior to study drug OR placebo)	Gastrointestinal disorders	—
Pain at pump site during MMTT (prior to delivery of study drug or placebo)	General disorders	—
Pruritis at pump insertion site during MMTT (prior to delivery of study drug or placebo)	Skin and subcutaneous tissue disorders	—
Feeling hot after alarm (glucagon visit)	General disorders	—
Headace after alarm (glucagon visit)	General disorders	—
Dizzy / lightheaded after alarm (glucagon visit)	General disorders	—
Tiredness after alarm (glucagon visit)	General disorders	—
Stomach cramping / pain after alarm (placebo visit)	Gastrointestinal disorders	—
Lower extremity cramping after alarm (glucagon visit)	Musculoskeletal and connective tissue disorders	—
Feeling hot after lunch (placebo visit)	General disorders	—
Headache after lunch (glucagon visit)	General disorders	—
Hyperkalemia at screening visit	Metabolism and nutrition disorders	—
MCH above normal limit of refrence range at screening visit.	Blood and lymphatic system disorders	—
WBC above normal limit of reference range at screening visit	Blood and lymphatic system disorders	—
Tiredness prior to start of MMTT	General disorders	—
Thirsty after intake of mixed meal (prior to study drug OR placebo)	General disorders	—
Bloated / uncomfortably full after intake of mixed meal (prior to study drug OR placebo)	Gastrointestinal disorders	—
Blurry vision after intake of mixed meal (prior to study drug OR placebo)	Eye disorders	—
Tingling (paresthesia) in shoulders after intake of mixed meal (prior to study drug or placebo)	General disorders	—
Tingling (paresthesia) around the mouth after intake of mixed meal (prior to study drug or placebo)	General disorders	—
Dizzy after intake of mixed meal (prior to study drug OR placebo)	General disorders	—
Feeling unwell ("icky... drunk") after intake of mixed meal (prior to study drug OR placebo)	General disorders	—

Most-reported serious reactions: Hypokalemia.

Data from ClinicalTrials.gov NCT03255629 adverse events section.

Sponsor's own description

To assess the efficacy of a closed loop glucagon system to prevent and treat hypoglycemia occurring in patients with Post-Bariatric Hypoglycemia (PBH) in response to meals and exercise.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Glycemic Patterns Are Distinct in Post-Bariatric Hypoglycemia After Gastric Bypass (PBH-RYGB).
   Lee D, Dreyfuss JM, Sheehan A, Puleio A, et al · · 2021 · cited 36× · PMID 33974064 · DOI 10.1210/clinem/dgab323
2. A Randomized, Placebo-Controlled Double-Blind Trial of a Closed-Loop Glucagon System for Postbariatric Hypoglycemia.
   Mulla CM, Zavitsanou S, Laguna Sanz AJ, Pober D, et al · · 2020 · cited 30× · PMID 31714583 · DOI 10.1210/clinem/dgz197
3. Managing post-bariatric hypoglycemia: a systematic review of pharmacological therapies.
   Sridharan K, Sivaramakrishnan G. · · 2025 · PMID 41126373 · DOI 10.1186/s13098-025-01988-y