Empagliflozin and Anakinra for the Treatment of Postprandial Hypoglycemia in Patients With Prediabetes
- Conditions
- Postprandial Hypoglycemia
- Interventions
- Other: saline subcutaneous (s.c.) (placebo)Other: tablet per oral (p.o.) (placebo)
- Registration Number
- NCT05174507
- Lead Sponsor
- University Hospital, Basel, Switzerland
- 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.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 26
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Group 1 (anakinra; placebo; empagliflozin) tablet per oral (p.o.) (placebo) Group 1: study day 1: anakinra; study day2: placebo; study day 3: empagliflozin Group 2 (placebo; anakinra; empagliflozin) saline subcutaneous (s.c.) (placebo) study day 1: placebo; study day2: anakinra; study day 3: empagliflozin Group 2 (placebo; anakinra; empagliflozin) tablet per oral (p.o.) (placebo) study day 1: placebo; study day2: anakinra; study day 3: empagliflozin Group 4 (empagliflozin; anakinra; placebo) saline subcutaneous (s.c.) (placebo) study day 1: empagliflozin; study day2: anakinra; study day 3: placebo Group 3 (empagliflozin; placebo; anakinra) tablet per oral (p.o.) (placebo) study day 1: empagliflozin; study day2: placebo; study day 3: anakinra Group 1 (anakinra; placebo; empagliflozin) saline subcutaneous (s.c.) (placebo) Group 1: study day 1: anakinra; study day2: placebo; study day 3: empagliflozin Group 3 (empagliflozin; placebo; anakinra) saline subcutaneous (s.c.) (placebo) study day 1: empagliflozin; study day2: placebo; study day 3: anakinra Group 5 (placebo; empagliflozin; anakinra) tablet per oral (p.o.) (placebo) study day 1: placebo; study day2: empagliflozin; study day 3: anakinra Group 4 (empagliflozin; anakinra; placebo) tablet per oral (p.o.) (placebo) study day 1: empagliflozin; study day2: anakinra; study day 3: placebo Group 6 (anakinra; empagliflozin; placebo) saline subcutaneous (s.c.) (placebo) study day 1:anakinra; study day2: empagliflozin; study day 3: placebo Group 5 (placebo; empagliflozin; anakinra) saline subcutaneous (s.c.) (placebo) study day 1: placebo; study day2: empagliflozin; study day 3: anakinra Group 6 (anakinra; empagliflozin; placebo) tablet per oral (p.o.) (placebo) study day 1:anakinra; study day2: empagliflozin; study day 3: placebo Group 1 (anakinra; placebo; empagliflozin) empagliflozin Group 1: study day 1: anakinra; study day2: placebo; study day 3: empagliflozin Group 1 (anakinra; placebo; empagliflozin) anakinra Group 1: study day 1: anakinra; study day2: placebo; study day 3: empagliflozin Group 2 (placebo; anakinra; empagliflozin) empagliflozin study day 1: placebo; study day2: anakinra; study day 3: empagliflozin Group 3 (empagliflozin; placebo; anakinra) anakinra study day 1: empagliflozin; study day2: placebo; study day 3: anakinra Group 2 (placebo; anakinra; empagliflozin) anakinra study day 1: placebo; study day2: anakinra; study day 3: empagliflozin Group 3 (empagliflozin; placebo; anakinra) empagliflozin study day 1: empagliflozin; study day2: placebo; study day 3: anakinra Group 4 (empagliflozin; anakinra; placebo) empagliflozin study day 1: empagliflozin; study day2: anakinra; study day 3: placebo Group 4 (empagliflozin; anakinra; placebo) anakinra study day 1: empagliflozin; study day2: anakinra; study day 3: placebo Group 5 (placebo; empagliflozin; anakinra) anakinra study day 1: placebo; study day2: empagliflozin; study day 3: anakinra Group 5 (placebo; empagliflozin; anakinra) empagliflozin study day 1: placebo; study day2: empagliflozin; study day 3: anakinra Group 6 (anakinra; empagliflozin; placebo) empagliflozin study day 1:anakinra; study day2: empagliflozin; study day 3: placebo Group 6 (anakinra; empagliflozin; placebo) anakinra study day 1:anakinra; study day2: empagliflozin; study day 3: placebo
- Primary Outcome Measures
Name Time Method Number of symptomatic hypoglycemia 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).
- Secondary Outcome Measures
Name Time Method Nadir plasma glucose (mmol/l) up to 3 hours after ingestion of the liquid mixed-meal Nadir plasma glucose (mmol/l)
Change in inflammatory state at baseline and 60 min after ingestion of the mixed meal 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)
Change in RNA sequencing (RNAseq) in peripheral PBMC at baseline and 60 min after ingestion of the mixed meal Change in RNAseq in peripheral PBMC
Change in proinsulin to insulin ratio in serum at baseline and 60 min after ingestion of the mixed meal Change in proinsulin to insulin ratio in serum
Severity of symptoms of hypoglycemia according to the Edinburgh Hypoglycemia Scale up to 3 hours after ingestion of the liquid mixed-meal 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
Trial Locations
- Locations (1)
Department of Endocrinology, Diabetes and Metabolism, University Hospital Basel
🇨🇭Basel, Switzerland