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Empagliflozin effect on glucose toxicity in type 2 diabetes patients - a randomized, open-label, controlled, parallel group, exploratory study
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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.
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Inclusion criteria
Subjects must fulfill all of the following criteria before inclusion in the study:
The informed consent form must be signed before any study specific tests or procedures are done
Male or female patients aged between 40 and 70 years (including) at the first screening visit
Patients diagnosed with T2DM
HbA1c between 7-9% (including)
Stable treatment with antidiabetic drugs over the last 4 weeks
Accepted background medication:
Linagliptin up to 5 mg per day Sitagliptin up to 100 mg per day Vildagliptin up to 100 mg per day Saxagliptin up to 5 mg per day
Exclusion criteria
Subjects are to be excluded from the study if they display any of the following criteria:
Unstable Angina pectoris, myocardial infarction or stroke within 1 year before inclusion in the study
History of atrial fibrillation
Uncontrolled arterial hypertension (> 160/100 mmHg in three subsequent measurements - mean value)
eGFR < 60 ml/min/1.73 m2
Macroalbuminuria defined as ≥ 300 mg albumin / 24h urine
Triglyceride > 250 mg/dl
Genetic muscle disease
Known coagulation disorder
Treatment with anti-platelet therapy and anticoagulation which cannot be paused for medical reasons
Treatment with anticoagulants within 7 days prior to the muscle biopsy
Contraindications according to the local SmPC of Lantus® or Jardiance® (see Appendix 1)
History of hypersensitivity to any of the study drugs or their ingredients or to drugs with similar structure or to the local anesthetic scandicaine or lidocaine
Addiction or other diseases that preclude the patient from appropriately assessing the nature and scope as well as possible consequences of the clinical study
Pregnant or breast-feeding women
Women of childbearing potential unless women who meet the following criteria:
Males must agree not to father a child and to refrain from donating semen or sperm while participating in the study and for 90 days following discontinuation from this study
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0 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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