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Effects of Dapagliflozin on Hormonal Glucose Homeostasis in Type 1 Diabetes

NCT04035031 · Status: COMPLETED · Phase: PHASE3 · Type: INTERVENTIONAL · Enrollment: 13

Last updated 2023-03-14

No results posted yet for this study

Summary

Inhibitors of sodium-dependent glucose-transporter 2 (including dapagliflozin) represent intensively investigated drugs in the field of diabetes. SGLT-2 inhibition limits glucose reabsorption in renal tubular cells, hereby increasing the amount of glucose excreted via urine in the hyperglycemic state. Its mechanisms of action are independent of insulin, the indispensable standard of care in Type 1 Diabetes (T1D). Several international diabetes experts highlighted the need for adjunct therapies in T1D.

Subcutaneous application of insulin is non-physiological. Most significant, subcutaneous insulin substitution does not address the bi-hormonal character of T1D. The loss of pancreatic beta cells and subsequent endogenous insulin production uncouples alpha cell derived glucagon secretion from its paracrine suppressor. Consequently, excess glucagon concentrations occur in the fasting and the postprandial state, which promotes hyperglycemia, requires higher doses of subcutaneous insulin, and promotes glycaemic variability.

Recent studies on SGLT-2 inhibition in T1D showed better glycemic control compared to placebo, whereas a higher risk for the development of diabetic ketoacidosis was observed. Knowledge about the underlying mechanisms is scarce. Studies showed that SGLT-inhibition increased Glucagon-like-peptide 1 (GLP-1) in T1D, an incretin hormone capable of suppressing glucagon. On the other side, total concentrations of ketone bodies were higher following SGLT-2 inhibition, irrespective of ongoing subcutaneous or intravenous insulin substitution. The present study aims to investigate the effect of SGLT-2 inhibitor dapagliflozin on hormonal regulators of glucose homeostasis and ketogenesis in T1D. The primary endpoint is the difference of GLP-1 during oral glucose tolerance test clamps (OGGTc). Secondary endpoints comprise total ketone body concentrations, free fatty acids, glucagon, and somatostatin during OGTTc and hyperinsulinemic, euglycemic clamps (HEC) following dapagliflozin and placebo. The study recruits male and female patients with T1DM in a randomized, open label, cross-over intervention study.

Conditions

  • Diabetes Mellitus, Type 1

Interventions

DRUG

Forxiga 10mg

Forxiga™ 10mg, dapagliflozin 10mg, oral, once daily for 7 days (70 mg total)

DRUG

Placebo

Placebo tablets, starch, oral, once daily for 7 days (7 tablets total)

Sponsors & Collaborators

  • Insel Gruppe AG, University Hospital Bern

    lead OTHER

Principal Investigators

  • Markus Laimer, Prof. MD · Department of Diabetes, Endocrinology, Clinical Nutrition and Metabolism, University Clinics Bern, Inselspital, Bern, Switzerland

Study Design

Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Model
CROSSOVER

Eligibility

Min Age
18 Years
Max Age
65 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2020-01-09
Primary Completion
2020-11-12
Completion
2020-11-12

Countries

  • Switzerland

Study Locations

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Entities

Drugs

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04035031 on ClinicalTrials.gov