NCT03437330

Empagliflozin Effect on Glucose Toxicity

Empagliflozin Effect on Glucose Toxicity in Type 2 Diabetes Patients - a Randomized, Open-label, Controlled, Parallel Group, Exploratory Study

• Status: Withdrawn
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: University Hospital Tuebingen · Academic / Other
• Sex: All
• Age: 40 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Empagliflozin effect on glucose toxicity in type 2 diabetes patients - a randomized, open-label, controlled, parallel group, exploratory study

Detailed description

The EMPA-REG outcome trial showed that empagliflozin on top of standard therapy for Type 2 diabetes mellitus (T2DM) resulted in superiority in terms of the primary composite cardiovascular endpoint (hazard ratio (1) = 0.86; 95% confidence interval \[CI\] 0.74-0.99; P value = 0.04), hospitalization for heart failure (-35%), cardiovascular mortality (-38%) and all-cause mortality (-32%, each p \< 0.001) (2). This reduction in mortality is not fully explained by the reduction in HbA1c, body weight, waist circumference and blood pressure in the empagliflozin groups versus the placebo group. Differences in mode of action of empagliflozin compared to standard therapy might, thus, help to explain why empagliflozin was so efficient in reducing cardiovascular death. The aim of the present study is to provide evidence for a reduction of skeletal muscle H2O2 levels, and consequently improvement in mitochondrial function, and restored methylation pattern of key transcription factors in skeletal muscle from patients with T2DM when treated with empagliflozin versus insulin glargine as the prototypical medication favoring glucose uptake into tissues. It is hypothesized that empagliflozin compared to insulin specifically reduces H2O2 concentrations in skeletal muscle of patients with T2DM, because it leads to excretion of glucose and lower glucose uptake in skeletal muscle (22), while insulin shifts the major part of excess glucose into skeletal muscle cells.

Conditions

• Type2 Diabetes Mellitus

Interventions

Type	Name	Description
DRUG	Empagliflozin (Jardiance®)	Empagliflozin Dose/frequency: 10 mg once daily for 12 weeks Route of administration: oral Reference group: Insulin glargine (Lantus®) Dose/frequency: see below FBG 6-7 mmol/L: +2 IU (stop when FBG is reduced by 0.5 mmol/L or documented hypoglycemia \< 3.9 mmol/L occurs) FBG 7-8 mmol/L: +4 IU (stop when FBG is reduced by 1.0 mmol/L or documented hypoglycemia \< 3.9 mmol/L occurs) FBG \> 8 mmol/L: +6 IU (stop when FBG is reduced by 1.5 mmol/L or documented hypoglycemia \< 3.9 mmol/L occurs)
DRUG	Insulin Glargine (Lantus®)	insulin glargine shall be titrated according to the following scheme: If FBG 6-7 mmol/L: reduce fasting glucose by 0.5 mmol/L If FBG 7-8 mmol/L: reduce fasting glucose by 0.75 mmol/L If FBG 8-9 mmol/L: reduce fasting glucose by 1.0 mmol/L Thus, insulin glargine doses should be adapted as follows: FBG 6-7 mmol/L: +2 IU (stop when FBG is reduced by 0.5 mmol/L or documented hypoglycemia \< 3.9 mmol/L occurs) FBG 7-8 mmol/L: +3IU (stop when FBG is reduced by 0.75 mmol/L or documented hypoglycemia \< 3.9 mmol/L occurs) FBG \> 8 mmol/L: +5 IU (stop when FBG is reduced by 1.0mmol/L or documented hypoglycemia \< 3.9 mmol/L occurs)

Timeline

• Start date: 2021-10-27
• Primary completion: 2023-05-03
• Completion: 2023-05-03
• First posted: 2018-02-19
• Last updated: 2024-05-16

Locations

2 sites across 1 country: Germany