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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
22
Treatment naive patients with bariatric bypass surgery will be given oral empagliflozin 25mg once daily for 20 days
Treatment naive patients with bariatric bypass surgery will be given oral placebo once daily for 20 days
Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital and University of Bern
Bern, Canton of Bern, Switzerland
Amplitude of change in plasma glucose (difference between peak and nadir plasma glucose concentration in mmol/L) during the mixed meal test.
On day 20 of the intake of either empagliflozin or placebo, participants undergo a mixed meal test. During the test, the amplitude of plasma glucose (difference between peak and nadir plasma glucose concentration in mmol/L) will be measured.
Time frame: The outcome will be assessed during the mixed-meal test on the day of the experimental visit at the end of each study period (day 20-24 of the respective study period).
Mean amplitude of glucose excursion (MAGE) based on CGM glucose
During the intake of empagliflozin and placebo, participants will wear a continuous glucose monitoring device. After V1 and V2, CGM data will be extracted and analysed. MAGE will be calculated based on CGM data obtained during each observation period.
Time frame: The outcome will be calculated from day 1 to day 20 of intake of IMP/Placebo (i.e. aggregated measures of the outcome will be calculated for each period). The first 3 days of data of each period will be discarded.
Mean coefficient of variability based on CGM glucose
During the intake of empagliflozin and placebo, participants will wear a continuous glucose monitoring device. After V1 and V2, CGM data will be extracted and analysed. The mean coefficient of variability will be calculated based on CGM data obtained during each observation period.
Time frame: The outcome will be calculated from day 1 to day 20 of intake of IMP/Placebo (i.e. aggregated measures of the outcome will be calculated for each period). The first 3 days of data of each period will be discarded.
Peak plasma glucose during mixed meal test
On day 20 of the intake of either empagliflozin or placebo, participants undergo a mixed meal test. During the test, the peak of plasma glucose (in mmol/L) will be documented.
Time frame: The outcome will be assessed during the mixed-meal test on the day of the experimental visit at the end of each study period (day 20-24 of the respective study period).
Percent time spent with CGM glucose >10.0mmol/L
During the intake of empagliflozin and placebo, participants will wear a continuous glucose monitoring device. After V1 and V2, CGM data will be extracted and analysed. Percent time spent with CGM glucose \>10.0mmol/L will be calculated based on CGM data obtained during each observation period.
Time frame: The outcome will be calculated from day 1 to day 20 of intake of IMP/Placebo (i.e. aggregated measures of the outcome will be calculated for each period). The first 3 days of data of each period will be discarded.
Proportion of participants experiencing hypoglycaemia (defined as plasma glucose<3.0mmol/L) during the mixed meal tolerance test
On day 20 of the intake of either empagliflozin or placebo, participants undergo a mixed meal test. During the test, the proportion of participants experiencing hypoglycaemia (defined as plasma glucose\<3.0mmol/L) will be documented.
Time frame: The outcome will be assessed during the mixed-meal test on the day of the experimental visit at the end of each study period (day 20-24 of the respective study period).
Nadir plasma glucose during mixed meal test
On day 20 of the intake of either empagliflozin or placebo, participants undergo a mixed meal test. During the test, the nadir of plasma glucose (in mmol/L) will be documented.
Time frame: The outcome will be assessed during the mixed-meal test on the day of the experimental visit at the end of each study period (day 20-24 of the respective study period).
Percent time spent with CGM glucose <3.0mmol/L
During the intake of empagliflozin and placebo, participants will wear a continuous glucose monitoring device. After V1 and V2, CGM data will be extracted and analysed. Percent time spent with CGM glucose \<3.0mmol/L will be calculated based on CGM data obtained during each observation period.
Time frame: The outcome will be calculated from day 1 to day 20 of intake of IMP/Placebo (i.e. aggregated measures of the outcome will be calculated for each period). The first 3 days of data of each period will be discarded.
Percent time spent with CGM glucose <2.8mmol/L
During the intake of empagliflozin and placebo, participants will wear a continuous glucose monitoring device. After V1 and V2, CGM data will be extracted and analysed. Percent time spent with CGM glucose \<2.8mmol/L will be calculated based on CGM data obtained during each observation period.
Time frame: The outcome will be calculated from day 1 to day 20 of intake of IMP/Placebo (i.e. aggregated measures of the outcome will be calculated for each period). The first 3 days of data of each period will be discarded.
Frequency of postprandial symptoms based on a modified Edinburgh Hypoglycaemia
During the intake of empagliflozin and placebo, participants will report postprandial symptoms in an electronic event diary. The frequency of postprandial symptoms, based on a modified Edinburgh Hypoglycaemia Symptom Scale, will be documented.
Time frame: The outcome will be calculated from day 1 to day 20 of intake of IMP/Placebo.
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