Postprandial HypoglycemiaPhase 2Hypo-PrEANCT05174507
Empagliflozin and Anakinra for the Treatment of Postprandial Hypoglycemia in Patients With Prediabetes
A Phase 2 study testing empagliflozin and anakinra in people with Postprandial Hypoglycemia, run by University Hospital, Basel, Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Postprandial Hypoglycemia
- What is being tested?
- empagliflozin and anakinra
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 24 Jun 2022to 1 May 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
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- 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.
About this study
Official title: 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.
Read the detailed 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.
- Conditions
- Postprandial Hypoglycemia
- Being tested
- empagliflozin, anakinra, saline subcutaneous (s.c.) (placebo), tablet per oral (p.o.) (placebo)
- Keywords
- SGLT2-inhibitor empagliflozin, IL-1 receptor antagonist anakinra, prediabetes, insulin clearance, proinsulin
- Medical subject headings
- Hypoglycemia, Prediabetic State, Diabetes Mellitus, Insulin-Dependent, 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
empagliflozinDrug
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).
anakinraDrug
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).
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).
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).
| Study group | Role | What they receive |
|---|---|---|
| Group 1 (anakinra; placebo; empagliflozin) | Other | Group 1:
study day 1: anakinra; study day2: placebo; study day 3: empagliflozin Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: empagliflozin; Drug: anakinra; Other: saline subcutaneous (s.c.) (placebo); Other: tablet per oral (p.o.) (placebo) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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
The Edinburgh Hypoglycemia Scale is a classification of the 11 most common symptoms of hypoglycemia. Subjective intensity-grading:
- no symptoms 0
- light symptoms 1
- moderate symptoms 2
- severe symptoms 3
Measured: up to 3 hours after ingestion of the liquid mixed-meal
Nadir plasma glucose (mmol/l)
Nadir plasma glucose (mmol/l)
Measured: up to 3 hours after ingestion of the liquid mixed-meal
Change in proinsulin to insulin ratio in serum
Change in proinsulin to insulin ratio in serum
Measured: at baseline and 60 min after ingestion of the mixed meal
Change in inflammatory state
Change in inflammatory laboratory parameters (Interleukin (IL)1ß, IL6, Tumor necrosis factor (TNF) α, IL-10, IL-1Ra) in supernatants of Lipopolysaccharide (LPS)-stimulated and unstimulated peripheral blood mononuclear cells (PBMC)
Measured: at baseline and 60 min after ingestion of the mixed meal
Change in RNA sequencing (RNAseq) in peripheral PBMC
Change in RNAseq in peripheral PBMC
Measured: at baseline and 60 min after ingestion of the mixed meal
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2021
- Study start24 Jun 2022
- Primary completion1 May 2026 (estimated)
- Study completion1 May 2026 (estimated)
Why it stopped: Sponsor- Investigator decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Postprandial HypoglycemiaStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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).
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marc Y. Donath, Prof. Dr. med., Principal investigator, Division of Endocrinology, Diabetes and Metabolism, University Hospital Basel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05174507
- Sponsor's protocol ID
- 2020-01287; me20Donath
- Acronym
- Hypo-PrEA
- Status last verified
- Feb 2026
- First submitted
- 13 Dec 2021
- Last updated
- 20 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Empagliflozin and Anakinra for the Treatment of Postprandial Hypoglycemia in Patients With Prediabetes: a Randomized, Placebo-controlled Study
- ClinicalTrials.gov ID
- NCT05174507
- Acronym / sponsor ID
- Hypo-PrEA / 2020-01287; me20Donath
- Conditions
- Postprandial Hypoglycemia
- Keywords
- SGLT2-inhibitor empagliflozin, IL-1 receptor antagonist anakinra, prediabetes, insulin clearance, proinsulin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor- Investigator decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- 24 Jun 2022 (actual)
- Primary completion
- 1 May 2026 (estimated)
- Study completion
- 1 May 2026 (estimated)
- First posted
- 30 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 6
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| Group 1 (anakinra; placebo; empagliflozin) | Other | Drug: empagliflozin, Drug: anakinra, Other: saline subcutaneous (s.c.) (placebo), Other: tablet per oral (p.o.) (placebo)Group 1: study day 1: anakinra; study day2: placebo; study day 3: empagliflozin |
| Group 2 (placebo; anakinra; empagliflozin) | Other | Drug: empagliflozin, Drug: anakinra, Other: saline subcutaneous (s.c.) (placebo), Other: tablet per oral (p.o.) (placebo)study day 1: placebo; study day2: anakinra; study day 3: empagliflozin |
| Group 3 (empagliflozin; placebo; anakinra) | Other | Drug: empagliflozin, Drug: anakinra, Other: saline subcutaneous (s.c.) (placebo), Other: tablet per oral (p.o.) (placebo)study day 1: empagliflozin; study day2: placebo; study day 3: anakinra |
| Group 4 (empagliflozin; anakinra; placebo) | Other | Drug: empagliflozin, Drug: anakinra, Other: saline subcutaneous (s.c.) (placebo), Other: tablet per oral (p.o.) (placebo)study day 1: empagliflozin; study day2: anakinra; study day 3: placebo |
| Group 5 (placebo; empagliflozin; anakinra) | Other | Drug: empagliflozin, Drug: anakinra, Other: saline subcutaneous (s.c.) (placebo), Other: tablet per oral (p.o.) (placebo)study day 1: placebo; study day2: empagliflozin; study day 3: anakinra |
| Group 6 (anakinra; empagliflozin; placebo) | Other | Drug: empagliflozin, Drug: anakinra, Other: saline subcutaneous (s.c.) (placebo), Other: tablet per oral (p.o.) (placebo)study day 1:anakinra; study day2: empagliflozin; study day 3: placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| empagliflozinEmpagliflozin (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). | Drug | 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) |
| anakinraAnakinra (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). | Drug | 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)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). | Other | 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)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). | Other | 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) |
Primary outcome
Number of symptomatic hypoglycemia
Time frame: up to 3 hours after ingestion of the liquid mixed-meal
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).
5 secondary outcomes
Severity of symptoms of hypoglycemia according to the Edinburgh Hypoglycemia Scale
Time frame: up to 3 hours after ingestion of the liquid mixed-meal
Nadir plasma glucose (mmol/l)
Time frame: up to 3 hours after ingestion of the liquid mixed-meal
Change in proinsulin to insulin ratio in serum
Time frame: at baseline and 60 min after ingestion of the mixed meal
Change in inflammatory state
Time frame: at baseline and 60 min after ingestion of the mixed meal
Change in RNA sequencing (RNAseq) in peripheral PBMC
Time frame: at baseline and 60 min after ingestion of the mixed meal
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc Y. Donath, Prof. Dr. med. principal investigator
Division of Endocrinology, Diabetes and Metabolism, University Hospital Basel
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing empagliflozin and anakinra in people with Postprandial Hypoglycemia, run by University Hospital, Basel, Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 20 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of symptomatic hypoglycemia (time frame: up to 3 hours after ingestion of the liquid mixed-meal). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2026.