Investigating the Impact of the SGLT2 Inhibitor Empagliflozin on Postprandial Hypoglycaemia After Gastric Bypass

NCT ID: NCT05057819

Last Updated: 2023-03-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-01
• Study Completion Date: 2022-08-11

Brief Summary

Bariatric surgery is an effective anti-obesity treatment providing durable weight loss and profound beneficial effects on glucose metabolism. However, bariatric surgery also comes with an increased risk for a late metabolic complication known as postbariatric hypoglycaemia (PBH). The condition presents with hypoglycaemic episodes 1-3 hours after meals and develops one to several years after bariatric surgery, mainly gastric bypass. PBH affects approximately 30% of patients without preexisting diabetes. For a subset of patients, hypoglycaemia-associated impairment of daily living and social functioning are commonly observed. The underlying mechanisms of PBH are multifactorial. It is considered that inadequately high insulin secretion caused by both accelerated glucose absorption from the gut and increased insulinotropic hormones such as GLP-1 are important pathophysiologic mechanisms. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor reduces glucose exposure by increasing urinary glucose excretion. In a pilot study, a single dose of 10mg of empagliflozin taken before a mixed meal reduced the risk of PBH by 74%. Both, postprandial glucose and insulin exposure were significantly lower with empagliflozin vs. placebo, which makes Empagliflozin a potential treatment for PBH. In this study, treatment naïve patients will be randomized to receive either oral empagliflozin 25 mg daily in the morning for 20 days, followed by 2-6 weeks wash out and 20 days placebo once daily in the morning, or the reverse sequence. Urine and blood analysis will be performed as detailed in the protocol.

Conditions

Dumping Syndrome; Hypoglycemia, Reactive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Empagliflozin first, Placebo second

Oral empagliflozin 25 mg daily in the morning for 20 days, followed by oral placebo (daily in the morning) for 20 days after a wash-out period of 2-6 weeks

Group Type: EXPERIMENTAL

Empagliflozin 25 MG

Intervention Type: DRUG

Treatment naive patients with bariatric bypass surgery will be given oral empagliflozin 25mg once daily for 20 days

Placebo

Intervention Type: DRUG

Treatment naive patients with bariatric bypass surgery will be given oral placebo once daily for 20 days

Placebo first, Empagliflozin second

Oral placebo (daily in the morning) for 20 days, followed by oral empagliflozin 25 mg daily in the morning for 20 days after a wash-out period of 2-6 weeks

Group Type: PLACEBO_COMPARATOR

Empagliflozin 25 MG

Intervention Type: DRUG

Treatment naive patients with bariatric bypass surgery will be given oral empagliflozin 25mg once daily for 20 days

Placebo

Intervention Type: DRUG

Treatment naive patients with bariatric bypass surgery will be given oral placebo once daily for 20 days

Interventions

Empagliflozin 25 MG

Treatment naive patients with bariatric bypass surgery will be given oral empagliflozin 25mg once daily for 20 days

Intervention Type: DRUG

Placebo

Treatment naive patients with bariatric bypass surgery will be given oral placebo once daily for 20 days

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Informed Consent as documented by signature
• Age 18 years or older
• Gastric bypass surgery ≥1 year ago
• Biochemically confirmed postprandial hypoglycaemia (plasma or sensor glucose <3.0mmol/l) within the past three months

Exclusion Criteria

• Diabetes on anti-diabetic treatment (insulin and/or non-insulin agents)
• Genito-urinary infection, if not treated successfully
• Chronic kidney disease (defined as CKD-EPI eGFR < 60 mL/min per 1.73 m2 body surface area)
• Pregnant and lactating women (urine pregnancy test to be performed for women of childbearing potential [defined as women who are not surgically sterilized/ hysterectomized, and/ or who are postmenopausal for less than 12 months]) or women of childbearing potential that refuse to use an effective contraceptive method [birth control pill or intrauterine device (IUD)]).
• Inability to understand and follow the protocol
• Known allergy to the study drug
• Participation in another interventional clinical trial overlapping with the current trial

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lia Bally, MD/PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland

Locations

Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital and University of Bern

Bern, Canton of Bern, Switzerland

Countries

Switzerland

References

Ferreira A, Schonenberger KA, Potoczna N, Vogt A, Gerber PA, Zehetner J, Giachino D, Nett P, Gawinecka J, Cossu L, Fuster DG, Dalla Man C, Facchinetti A, Melmer A, Nakas CT, Hepprich M, Donath MY, Herzig D, Bally L. Randomized, Double-Blind, Placebo-Controlled Crossover Trial of Once Daily Empagliflozin 25 mg for the Treatment of Postprandial Hypoglycemia After Roux-en-Y Gastric Bypass. Diabetes Technol Ther. 2023 Jul;25(7):467-475. doi: 10.1089/dia.2023.0036. Epub 2023 Jun 5.

Reference Type: DERIVED

PMID: 37093196 (View on PubMed)

Ferreira A, Emara AFA, Herzig D, Melmer A, Vogt AP, Nakas CT, Facchinetti A, Dalla Man C, Bally L. Study protocol for a randomised, double-blind, placebo-controlled crossover trial assessing the impact of the SGLT2 inhibitor empagliflozin on postprandial hypoglycaemia after gastric bypass. BMJ Open. 2022 Sep 19;12(9):e060668. doi: 10.1136/bmjopen-2021-060668.

Reference Type: DERIVED

PMID: 36123073 (View on PubMed)

Other Identifiers

DEEP-Empa

Identifier Type: -

Identifier Source: org_study_id