Phase 4
Completed N=12
Dapagliflozin and Cholesterol Metabolism in Type 2 Diabetes (DM2)
Source: ClinicalTrials.gov NCT03074630 ↗Enrolled (actual)
12
Serious AEs
0.0%
Results posted
Aug 2020
Primary outcomePrimary: Change in Plasma LDL Cholesterol — -0.1 mmol/L
◆ Published Evidence
No publication linked
No peer-reviewed publication reporting this trial's results has been linked yet. This can indicate results are unpublished — a known publication-bias signal. We re-check periodically.
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% - 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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Plasma LDL Cholesterol |
-0.1 | — |
| SECONDARY Change in Plasma HDL Cholesterol |
0.08 | — |
| SECONDARY Change in Total Cholesterol |
-0.01 | — |
| SECONDARY Change in Plasma Triglycerides |
0.10 | — |
| SECONDARY Change in Plasma FFA |
0.20 | — |
| SECONDARY Change in Cholesterol Fluxes |
— | — |
| SECONDARY Change in Triglyceride Fluxes |
— | — |
| SECONDARY Change in Peripheral Insulin Sensitivity |
1.6 | — |
| SECONDARY Liver Fat MRI Spectrum |
— | — |
| SECONDARY Fecal Microbiome Composition |
— | — |
| SECONDARY Bile Salt Excretion |
— | — |
| SECONDARY Urinary Glucose Excretion |
44 | — |
| SECONDARY Urinary Sodium Excretion |
— | — |
Eligibility Criteria
Inclusion Criteria
- Male or postmenopausal female patients ;
- Type 2 diabetes mellitus(HbA1C ≥6.5% - 2.5 mmol/l
- Willing to switch used statin to rosuvastatin 10mg once daily
- 18-75 years of age
- Ability to provide informed consent
Exclusion Criteria
- History of cardiovascular event
- Smoking
- exogenous insulin use
- Creatinin clearance 4 units/day)
- AST or ALT elevation (>2.5x upper limit)
- Contraindication to MR scanning (i.e. pacemaker, metallic foreign body, claustrophobia)
Data sourced from ClinicalTrials.gov (NCT03074630). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.