Dapagliflozin and Cholesterol Metabolism in Type 2 Diabetes (DM2)

Sponsor
Amsterdam UMC, location VUmc
Study ID
NCT03074630
Phase
PHASE4
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Dapagliflozin — DRUG
    5 weeks 10mg dapagliflozin once daily
  • Rosuvastatin — DRUG
    9 weeks 10mg dapagliflozin once daily

Study Details

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.

Key Dates

Start date
May 31, 2016
Status verified
Jul 2020
Primary completion
Apr 30, 2018
Completion
Apr 30, 2018

Study Design

Enrollment
12 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE

Arms

  • Experimental: Dapagliflozin 10mg and Rosuvastatin 10mg
    Rosuvastatin 10mg once daily for 9 weeks, with 5 weeks of once daily Dapagliflozin 10mg added

Primary Outcome Measure

Change in Plasma LDL Cholesterol [ Time Frame: 5 weeks ]

Related Studies