Empagliflozin and Anakinra for the Treatment of Postprandial Hypoglycemia in Patients With Prediabetes

Empagliflozin and Anakinra for the Treatment of Postprandial Hypoglycemia in Patients With Prediabetes: a Randomized, Placebo-controlled Study

This study is to analyze whether the SGLT2-inhibitor empagliflozin or the IL-1 receptor antagonist anakinra may improve postprandial hypoglycemia in subjects with prediabetes.

Subjects with prediabetes may develop postprandial hypoglycemia. This is probably due to a dysfunction of the insulin producing β-cell characterized by a delayed and exaggerated insulin secretion leading to an initial peak in glycaemia followed by a rapid fall and eventually resulting in hypoglycemia. The latter occurring typically within 1 to 3 hours after food intake.

In patients with gastric bypass surgery and postprandial hypoglycemia the SGLT2-inhibitor empagliflozin and the IL-1 receptor antagonist anakinra reduced postprandial insulin release and prevented hypoglycemia. This study is to analyze whether a similar therapeutic approach using empagliflozin and anakinra may also improve postprandial hypoglycemia in subjects with prediabetes.

Inclusion Criteria:

• Subjects with prediabetes defined by Glycosylated haemoglobin A1c (HbA1c) 5.7-6.4 % or fasting plasma glucose 6.1-6.9 mmol/l) or plasma glucose 2 h following 75 glucose ingestion of 7.8-11.0 mmol/l.
• Hypoglycemia occuring 1 to 3 h following ingestion of a standardized liquid mixed-meal (75 g carbohydrates) and fulfilling the Whipple's triad (glucose below 3.0 mmol/l).
• Age ≥ 18 years
• For subjects with reproductive potential, willingness to use contraceptive measures adequate to prevent the subject from becoming pregnant during the study

Exclusion Criteria:

• Upper gastrointestinal surgery
• Diagnosis of any type of diabetes mellitus
• Signs of current infection
• Use of investigational drug up to one week prior to start of treatment phase
• Glucocorticoid therapy
• Neutropenia (leukocyte count < 1.5 × 109/L or absolute neutrophil count (ANC) < 0.5 × 109/L)
• Anemia (hemoglobin < 11 g/dL for males, < 10 g/dL for females)
• Clinically significant kidney or liver disease (creatinine > 1.5 mg/dL, aspartate aminotransferase (AST)/ALT > 2 × ULN, alkaline phosphatase > 2 × ULN, or total bilirubin [tBili] > 1.5 × ULN)
• Uncontrolled disease
• Currently pregnant or breastfeeding
• No subjects meeting the criteria for vulnerability
• Participation in another study with investigational drug within the 30 days preceding and during the present study.