Dapagliflozin in Physical Exercise in Type 1 Diabetes

NCT ID: NCT04049110

Last Updated: 2023-08-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-25
• Study Completion Date: 2023-05-10

Brief Summary

Inhibitors of sodium-dependent glucose-transporter 2 (SGLT-2 inhibitors, including dapagliflozin) inhibit glucose reabsorption in renal tubular cells, hereby increasing glycosuria in the hyperglycemic state. Its mechanisms of action are independent of insulin, which makes SGLT-2 inhibitors a potential adjunct to insulin in type 1 diabetes mellitus (T1DM).

However, a higher risk for diabetic ketoacidosis (DKA) was reported in patients with T1DM taking SGLT-2 inhibitors. DKA depends on an accumulation of ketone bodies in the blood stream, which equals an accumulation of acids that lead to acidosis. The underlying mechanisms of this observation are unknown. Ketone body production depends on the molar ratio of glucagon to insulin, with insulin suppressing but glucagon stimulating ketone body production. This translates into higher production during relative insulin deficiency, carbohydrate deficiency, and prolonged fasting, which occurs during sickness but also physical exercise. Physical exercise is a recommended cornerstone in the treatment of T1DM and current treatment guidelines recommend both, reductions of insulin doses and ingestion of additional carbohydrates to avoid hypoglycemic events. These adaptions might increase relative insulin deficiency, hyperglycemia and glycaemic variability, which might in turn promote ketone body production. The addition of SGLT-2 inhibitors further may promote ketogenesis even though there are reports of SGLT-2 inhibitors increase Glucagon-like-peptide-1 (GLP-1) in patients with T1DM. GLP-1 is a suppressor of glucagon secretion. In summary, knowledge about the effects of SGLT-2 inhibition on ketone body production is scarce, especially during exercise in patients with T1DM.

The study seeks to illustrate the effect of SGLT-2 inhibition on glycemic variability and ketone body production during and after recreational exercise in patients with T1DM. The results of study 2 will provide the basis for future studies investigating the underlying mechanisms of potentially modified ketone body production during and after exercise under SGLT-2 inhibition.

Conditions

Diabetes Mellitus, Type 1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Dapagliflozin first, placebo second

Dapagliflozin followed by placebo

Group Type: EXPERIMENTAL

Forxiga 10mg

Intervention Type: DRUG

Dapagliflozin 10mg per 24 hours, oral, for 7 consecutive days

Placebo

Intervention Type: DRUG

Placebo 1 tablet per 24 hours, oral, for 7 consecutive days

Placebo first, Dapagliflozin second

Placebo followed by dapagliflozin

Group Type: EXPERIMENTAL

Forxiga 10mg

Intervention Type: DRUG

Dapagliflozin 10mg per 24 hours, oral, for 7 consecutive days

Placebo

Intervention Type: DRUG

Placebo 1 tablet per 24 hours, oral, for 7 consecutive days

Interventions

Forxiga 10mg

Dapagliflozin 10mg per 24 hours, oral, for 7 consecutive days

Intervention Type: DRUG

Placebo

Placebo 1 tablet per 24 hours, oral, for 7 consecutive days

Intervention Type: DRUG

Other Intervention Names

Dapagliflozin

Eligibility Criteria

Inclusion Criteria

• Written informed consent
• Diagnosis of T1DM
• Duration of T1DM > 5 years
• Male or female sex
• Insulin therapy via multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII)
• Body mass index (BMI) between 20 and 29 kg/m2
• Adherence to sufficient contraceptive measures (double barrier method combining hormonal with mechanical barriers).
• Ability to perform a 60 minutes exercise session at 50% VO2max.

Exclusion Criteria

• Diagnosis of renal and/or hepatic dysfunction
• History of malignancy of any kind
• Intake of drugs influencing glucose homeostasis during the last three months
• Alcohol or drug abuse
• Inadequate vein status on both forearms
• Active smoker
• Known pregnancy, positive plasma beta human choriogonadotropine test prior to study inclusion or intention to become pregnant during the study period.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christoph Stettler, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

Department of Diabetes, Endocrinology, Clinical Nutrition and Metabolism, University Clinics Bern, Inselspital, Bern, Switzerland

Locations

Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

Bern, , Switzerland

Countries

Switzerland

Other Identifiers

CUI_002_02

Identifier Type: -

Identifier Source: org_study_id