NCT04049110

Dapagliflozin in Physical Exercise in Type 1 Diabetes

Completed Phase 3 Last updated 31 August 2023

What this trial tests

Phase 3 trial testing Forxiga 10mg in Diabetes Mellitus, Type 1 in 39 participants. Completed in 10 May 2023.

Timeline

25 August 2020

Primary endpoint
26 April 2023

10 May 2023

Quick facts

Lead sponsor	Insel Gruppe AG, University Hospital Bern
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	none
Primary purpose	basic science
Enrollment	39
Start date	25 August 2020
Primary completion	26 April 2023
Estimated completion	10 May 2023
Sites	1 location across Switzerland

Drugs / interventions tested

• Forxiga 10mg — full drug profile →
• Placebo

Conditions studied

• Diabetes Mellitus, Type 1 — all drugs for Diabetes Mellitus, Type 1 →

Sponsor

Insel Gruppe AG, University Hospital Bern

Who can join

Adults 18 to 65, any sex, with Diabetes Mellitus, Type 1. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. SGLT2 inhibitors: from glucose-lowering to cardiovascular benefits.
   Preda A, Montecucco F, Carbone F, Carbone F, et al · · 2024 · cited 76× · PMID 38456601 · DOI 10.1093/cvr/cvae047
2. The emergence of obesity in type 1 diabetes.
   Kueh MTW, Chew NWS, Al-Ozairi E, le Roux CW. · · 2024 · cited 57× · PMID 38092958 · DOI 10.1038/s41366-023-01429-8
3. SGLT2 Inhibitors in the Management of Type 1 Diabetes (T1D): An Update on Current Evidence and Recommendations.
   Maffei P, Bettini S, Busetto L, Dassie F. · · 2023 · cited 31× · PMID 37964939 · DOI 10.2147/dmso.s240903