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

Insel Gruppe AG, University Hospital Bern

Status and phase: Completed; Phase 4

Conditions: Hypoglycemia, Reactive; Dumping Syndrome

Treatments: Drug: Placebo; Drug: Empagliflozin 25 MG

Study type: Interventional

Funder types: Other

Identifiers

NCT05057819

DEEP-Empa

Details and patient eligibility

About

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.

Enrollment: 22 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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22 participants in 2 patient groups, including a placebo group

Empagliflozin first, Placebo second

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: Empagliflozin 25 MG

Placebo first, Empagliflozin second

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Drug: Empagliflozin 25 MG