This randomized trial is to test whether a treatment with empagliflozin is superior to placebo in patients with postprandial hypoglycemia after bariatric surgery, that is if it improves health related quality of life (mentally or physically) or reduces the risk of hypoglycemic events.
Postprandial hypoglycemia is a debilitating medical complication after bariatric surgery for which no approved pharmacological treatment exists. The prevalence of hypoglycemia in bariatric patients ranges from 0.5 % severe episodes up to 56 % and its symptoms range from asymptomatic to deleterious. This hypoglycemic condition is characterized by a rapid increase of plasma glucose after carbohydrate ingestion followed by an exaggerated hyperinsulinemic response. Hypoglycemia itself may lead to increased hunger, carbohydrate ingestion and following weight regain. In a placebo-controlled, randomized, double-blind, crossover study, the SGLT2-inhibitor empagliflozin statistically significantly reduced the number of symptomatic hypoglycemia (2 vs. 7 symptomatic hypoglycemic episodes; p=0.013) compared to placebo after a mixed meal test in 12 patients after Roux-en-Y gastric bypass. Empagliflozin reduced the postprandial rise in glycemia and decreased subsequent insulin secretion, underlining the postulated mechanism of action. This randomized trial is to test whether a treatment with empagliflozin is superior to placebo in patients with postprandial hypoglycemia after bariatric surgery, that is if it improves health related quality of life (mentally or physically) or reduces the risk of hypoglycemic events.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
40
Each tablet contains the active substance of 10 mg empagliflozin as well as the adjuvant lactose-monohydrate and is taken orally once daily in the morning.
Placebo will be provided by Boehringer Ingelheim. It is identical to the interventional product apart from the active compound.
University Hospital Basel, Division of Endocrinology, Diabetes and Metabolism
Basel, Switzerland
University Hospital Berne and Center of Bariatric Surgery Berne
Bern, Switzerland
Cantonal Hospital Olten, Endocrine Outpatient Clinic
Olten, Switzerland
Change in Quality of life (mental health; as assessed by the SF-36 mental health component score; MCS)
Change in Quality of life (mental health; as assessed by the SF-36 mental health component. Each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. Scores represent the percentage of total possible score achieved.
Time frame: at baseline, at day 29 and at day 60 (+/- 10 days) after baseline
Change in Quality of life (physical health; as assessed by the SF-36 mental physical component score; PCS)
Change in Quality of life (physical health; as assessed by the SF-36 mental physical component score; PCS). Each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. Scores represent the percentage of total possible score achieved.
Time frame: at baseline, at day 29 and at day 60 (+/- 10 days) after baseline
Hypoglycemic events defined as glucose values below 3.0 mmol/l
Hypoglycemic events defined as glucose values below 3.0 mmol/l
Time frame: at 28 days after randomization
Postprandial Symptoms of hypoglycemia defined as acute onset of typical symptoms according to Edinburgh Hypoglycemia Scale along with a decreasing blood glucose level.
Postprandial Symptoms of hypoglycemia defined as acute onset of typical symptoms according to Edinburgh Hypoglycemia Scale (7-point Likert scale (1 = not present, 7 = very intense)) along with a decreasing blood glucose level. The postprandial period is defined as 3 hours following meal intake.
Time frame: at 28 days after randomization
Hypoglycemia unawareness (measured by modified Clarke Score)
Hypoglycemia unawareness (measured by modified Clarke Score). The Clarke method comprises eight questions characterizing the participant's exposure to episodes of moderate and severe hypoglycemia. It also examines the glycemic threshold for, and symptomatic responses to, hypoglycemia. A score of four or more implies impaired awareness of hypoglycemia.
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Time frame: at 28 days after randomization
Fear of hypoglycemia (measured on a scale of 0 to 10)
Fear of hypoglycemia (measured on a scale of 0 to 10)
Time frame: at 28 days after randomization
Time below range (TBR): % of sensor glucose readings and time between 3.0 and 3.8 mmol/L)
Time below range (TBR): % of sensor glucose readings and time between 3.0 and 3.8 mmol/L)
Time frame: at 28 days after randomization
Time in hypoglycemia: % of sensor glucose readings and time below 3.0 mmol/L
Time in hypoglycemia: % of sensor glucose readings and time below 3.0 mmol/L
Time frame: at 28 days after randomization
Pattern of sensor glucose
Pattern of sensor glucose, defined as the slope of postprandial increase (calculated as the maximal rate of increase observed over 20min in the postprandial period) and decrease (calculated as the maximal rate of decrease over 20min in the postprandial period).
Time frame: at 28 days after randomization
Glycemic variability
Glycemic variability (defined as the coefficient of variation (CV) of sensor glucose)
Time frame: at 28 days after randomization
Mean amplitude of sensor glucose excursions (MAGE)
Mean amplitude of sensor glucose excursions (MAGE)
Time frame: at 28 days after randomization
Total number of adverse events
Total number of adverse events
Time frame: up to 60 days after randomization
Number of Serious adverse events
Number of Serious adverse events
Time frame: up to 60 days after randomization