Dapagliflozin and Cholesterol Metabolism in Type 2 Diabetes (DM2)
Status:
Completed
Trial end date:
2018-04-01
Target enrollment:
Participant gender:
Summary
Objective: To investigate the effect of 5 weeks dapagliflozin 10 mg once daily treatment on
glucose and lipid fluxes in patients with type 2 diabetes.
Study design: Single center single arm (mechanistic) intervention trial.
Study Population: Male or postmenopausal female patients with type 2 diabetes BMI > 25
kg/m2and more than 12 weeks a stable dose of metformin treatment > 1500mg, HbA1C ≥6.5% -
<8.5%, Fasting Plasma Glucose (FPG) <13.2 mmol/l, LDL cholesterol >2.5 mmol/l, willing to
switch to rosuvastatin 10mg once daily for 4 weeks, and then receive 10 mg dapagliflozin once
daily orally, for 5 weeks.
Treatment: After a statin washout fase of 4 weeks, baseline cholesterol synthesis will be
measured (2H3 Leucine, 2H2O deuterated water). Then, treatment with rosuvastatin 10mg for 4
weeks will be initiated after which, patients will undergo glucose (2H2enriched glucose) and
lipid flux (2H3 Leucine, 2H2O deuterated water and oral 1,2,3,4-13C16 - palmitate enrichment
measurements) followed by 5 weeks treatment with dapagliflozin 10mg once daily. In the final
week glucose/lipid flux measurements will be repeated.
Sample Size: 12 DM2 subjects.
Outcome measures: The primary endpoint is effect of 5 weeks Sodium-Glucose Linked
co-transporter (SGLT) 2 inhibition on LDL cholesterol synthesis in patients with DM2.
Secondary endpoints are effect of SGLT2 inhibition on triglyceride and cholesterol fluxes as
well as (hepatic and peripheral) insulin sensitivity and energy expenditure. Finally, effect
of SGLT2 inhibition on dietary intake, liver fat content (MRI liver) and fecal microbiome
will be studied at these timepoints.
Phase:
Phase 4
Details
Lead Sponsor:
VU University Medical Center
Collaborator:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)