Empagliflozin and Anakinra for the Treatment of Postprandial Hypoglycemia in Patients With Prediabetes (Hypo-PrEA)

University Hospital Basel

Status and phase: Active, not recruiting; Phase 2

Conditions: Postprandial Hypoglycemia

Treatments: Drug: anakinra; Drug: empagliflozin; Other: tablet per oral (p.o.) (placebo); Other: saline subcutaneous (s.c.) (placebo)

Study type: Interventional

Funder types: Other

Identifiers

NCT05174507

2020-01287 me20Donath;

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 26 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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26 participants in 6 patient groups

Group 1 (anakinra; placebo; empagliflozin)

Other group

Description:

Group 1: study day 1: anakinra; study day2: placebo; study day 3: empagliflozin

Treatment:

Other: tablet per oral (p.o.) (placebo)

Other: saline subcutaneous (s.c.) (placebo)

Drug: empagliflozin

Drug: anakinra

Group 2 (placebo; anakinra; empagliflozin)

Other group

Description:

study day 1: placebo; study day2: anakinra; study day 3: empagliflozin

Treatment:

Other: tablet per oral (p.o.) (placebo)

Other: saline subcutaneous (s.c.) (placebo)

Drug: empagliflozin

Drug: anakinra

Group 3 (empagliflozin; placebo; anakinra)

Other group

Description:

study day 1: empagliflozin; study day2: placebo; study day 3: anakinra

Treatment:

Other: tablet per oral (p.o.) (placebo)

Other: saline subcutaneous (s.c.) (placebo)

Drug: empagliflozin

Drug: anakinra

Group 4 (empagliflozin; anakinra; placebo)

Other group

Description:

study day 1: empagliflozin; study day2: anakinra; study day 3: placebo

Treatment:

Other: tablet per oral (p.o.) (placebo)

Other: saline subcutaneous (s.c.) (placebo)

Drug: empagliflozin

Drug: anakinra

Group 5 (placebo; empagliflozin; anakinra)

Other group

Description:

study day 1: placebo; study day2: empagliflozin; study day 3: anakinra

Treatment:

Other: tablet per oral (p.o.) (placebo)

Other: saline subcutaneous (s.c.) (placebo)

Drug: empagliflozin

Drug: anakinra

Group 6 (anakinra; empagliflozin; placebo)

Other group

Description:

study day 1:anakinra; study day2: empagliflozin; study day 3: placebo

Treatment:

Other: tablet per oral (p.o.) (placebo)

Other: saline subcutaneous (s.c.) (placebo)

Drug: empagliflozin

Drug: anakinra