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

NCT05174507 | Withdrawn Phase 2

• 1 other identifier: 2020-01287; me20Donath
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Postprandial Hypoglycemia

Keywords

SGLT2-inhibitor empagliflozin; IL-1 receptor antagonist anakinra; prediabetes; insulin clearance; proinsulin

Outcome Measures

Primary Outcomes (1)

• Number of symptomatic hypoglycemia

  Incidence of symptomatic hypoglycemia following a standardized mixed-meal test defined by appearance of typical symptoms, blood glucose level below 3.0 mmol/l and relief of symptoms when the glucose level is raised (Whipple's triad).

  up to 3 hours after ingestion of the liquid mixed-meal

Secondary Outcomes (5)

• Severity of symptoms of hypoglycemia according to the Edinburgh Hypoglycemia Scale

  up to 3 hours after ingestion of the liquid mixed-meal

• Nadir plasma glucose (mmol/l)

  up to 3 hours after ingestion of the liquid mixed-meal

• Change in proinsulin to insulin ratio in serum

  at baseline and 60 min after ingestion of the mixed meal

• Change in inflammatory state

  at baseline and 60 min after ingestion of the mixed meal

• Change in RNA sequencing (RNAseq) in peripheral PBMC

  at baseline and 60 min after ingestion of the mixed meal

Study Arms (6)

Group 1 (anakinra; placebo; empagliflozin)

OTHER

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

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

Group 2 (placebo; anakinra; empagliflozin)

OTHER

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

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

Group 3 (empagliflozin; placebo; anakinra)

OTHER

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

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

Group 4 (empagliflozin; anakinra; placebo)

OTHER

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

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

Group 5 (placebo; empagliflozin; anakinra)

OTHER

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

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

Group 6 (anakinra; empagliflozin; placebo)

OTHER

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

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

Interventions

empagliflozin DRUG

Empagliflozin (Jardiance®; Boehringer Ingelheim (Schweiz) GmbH) is a highly selective, reversible inhibitor of the sodium glucose co-transporter 2 (SGLT2). Treatment consists of a single oral tablet of 25 mg of empagliflozin (Jardiance®) two hours before ingestion of the mixed-meal (Ensure plus® 375 ml, 75 g carbohydrates, 562 kcal, drinking time 5 minutes).

Group 1 (anakinra; placebo; empagliflozin); Group 2 (placebo; anakinra; empagliflozin); Group 3 (empagliflozin; placebo; anakinra); Group 4 (empagliflozin; anakinra; placebo); Group 5 (placebo; empagliflozin; anakinra); Group 6 (anakinra; empagliflozin; placebo)

saline subcutaneous (s.c.) (placebo) OTHER

Placebo for anakinra is 0.67 ml of sterile 0.9 % saline solution s. c. Treatment consists of a single subcutaneous injection of matched placebo (0.67 ml of 0.9 % saline) three hours before ingestion of the mixed-meal (Ensure plus® 375 ml, 75 g carbohydrates, 562 kcal, drinking time 5 minutes).

Group 1 (anakinra; placebo; empagliflozin); Group 2 (placebo; anakinra; empagliflozin); Group 3 (empagliflozin; placebo; anakinra); Group 4 (empagliflozin; anakinra; placebo); Group 5 (placebo; empagliflozin; anakinra); Group 6 (anakinra; empagliflozin; placebo)

tablet per oral (p.o.) (placebo) OTHER

Placebo for empagliflozin is Winthrop P® (Zentiva, Frankfurt/Main) lactose tablet. Treatment consists of a single oral tablet of matched placebo two hours before ingestion of the mixed-meal (Ensure plus® 375 ml, 75 g carbohydrates, 562 kcal, drinking time 5 minutes).

Group 1 (anakinra; placebo; empagliflozin); Group 2 (placebo; anakinra; empagliflozin); Group 3 (empagliflozin; placebo; anakinra); Group 4 (empagliflozin; anakinra; placebo); Group 5 (placebo; empagliflozin; anakinra); Group 6 (anakinra; empagliflozin; placebo)

anakinra DRUG

Anakinra (Kineret®; r-metHuIL-1ra, Swedish Orphan Biovitrum AB) is a recombinant, non-glycosylated form of the human interleukin-1 receptor antagonist (IL-1Ra) in a 100 mg/0.67ml solution for SC injection. Treatment consists of a single subcutaneous injection of 100 mg Anakinra (Kineret®) three hours before ingestion of the mixed-meal (Ensure plus® 375 ml, 75 g carbohydrates, 562 kcal, drinking time 5 minutes).

Group 1 (anakinra; placebo; empagliflozin); Group 2 (placebo; anakinra; empagliflozin); Group 3 (empagliflozin; placebo; anakinra); Group 4 (empagliflozin; anakinra; placebo); Group 5 (placebo; empagliflozin; anakinra); Group 6 (anakinra; empagliflozin; placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

MeSH Terms

Conditions

Hypoglycemia; Prediabetic State; Diabetes Mellitus, Insulin-Dependent, 2

Interventions

empagliflozin; Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Marc Y. Donath, Prof. Dr. med.

  Division of Endocrinology, Diabetes and Metabolism, University Hospital Basel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Participants, investigators and study nurses will be blinded to the study drug.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Placebo controlled, double-blind, randomized, cross-over proof-of-concept study. Subjects will be randomized to either group 1-6 (ratio 1:1, in blocks of 4 participants).

Study Record Dates

• First Submitted: December 13, 2021
• First Posted: December 30, 2021
• Study Start: June 24, 2022
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: February 20, 2026

Record last verified: 2026-02

Locations

CH (1)