to investigate the effect of 5 weeks dapagliflozin 1dd 10mg treatment on glucose and cholesterol fluxes in patients with type 2 diabetes on stable rosuvastatin treatment.
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
effect of 5 weeks dapagliflozin 10mg on top of rosuvastatin treatment on LDL de
novo lipogenesis compared to rosuvastatin 10mg therapy only or no medication
Secondary outcome
Effect of 5 weeks dapagliflozin 10mg on:
-Change in VLDL secretion and clearance (as determined by 2H3 Leucine
enrichment) and relation to plasma CETP, PLTP and HDL subfractions
- (dietary) Triglyceride fluxes (as determined by 1,2,3,4-13C16 * palmitate
to measure FFA remnant uptake).
- hepatic and peripheral insulin sensitivity (2 step Hyperinsulinemic
normoglycemic clamp with 2H2enriched glucose:) and energy expenditure
including carbohydrate oxidation and fatty acid oxidation rates in breathing air
- liver fat content (MRI liver)
-change in fecal microbiome composition
-cholesterol and bile salt excretion
Background summary
Type 2 diabetes is associated with increased cardiovascular risk which is
driven by hyperglycemia en dyslipidemia. A few years ago, a new glucose
lowering medication of the SGLT2 inhibitors class (Dapagliflozin).was
registered in the Netherlands. Dapagliflozin has been tested in relatively
large studies and was effective in reducing HbA1c levels; however, a sideeffect
of all SGLT2 inhibitors is the increase in plasma cholesterol (LDL, HDL and
triglyceriden) with 5-8%. We would like to investigate what is mechanism is
driving the increased plasma cholesterol (hepatic cholesterol synthesis,
increased (dietary) intestinal cholesterol uptake in de darm or decreased
excretion of cholesterol) and moreover whether this dyslipidemia might reduce
the beneficial cardiovascular effects of glucose lowering by dapagliflozin.
Study objective
to investigate the effect of 5 weeks dapagliflozin 1dd 10mg treatment on
glucose and cholesterol fluxes in patients with type 2 diabetes on stable
rosuvastatin treatment.
Study design
open label single arm intervention study
Intervention
dapagliflozin 10mg once daily for 5 weeks and rosuvastatin 10mg 1dd during 9
weeks
Study burden and risks
Patients will bring 5 visits to the AMC (total 46 hours) during 13 weken; in
total 470 ml blood is drawn. Infusion of stable isotopes, liver MRI and
hyperinsulinemic clamp procedures are a safe and standard procedure at our
department (METC 2013_071) and are not associated with increased risk.
Rosuvastatin and dapagliflozin have been registered in the Nederlands and are
frequently used in patients with type 2 diabetes and their use is not
associated with increased risks. In conclusion, this is a low-moderate risk
study and we feel that the burden of the study and its potential risks do not
outweigh the benefits of increased pathophysiological insight into the drivers
of dyslipidemia upon SGLT2 use in patients with type 2 diabetes mellitus.
Meibergdreef 9 kamer F4-159.2
Amsterdam 1105 AZ
NL
Meibergdreef 9 kamer F4-159.2
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
-Male or postmenopauzal female patients with type 2 diabetes mellitus(HbA1C *6.5% - <8.5%)
-At least 12 weeks of stable dose metformin treatment, FPG<13.2 mmol/l
-LDL cholesterol >2.5 mmol/l
-Willing to switch used statin to rosuvastatin 10mg once daily for 9 weeks
-18-75 years of age
-Ability to provide informed consent
Exclusion criteria
-History of cardiovascular event
-Smoking
-exogenous insulin use
-Creatinin clearance < 60ml/min
-Alcohol abuse (>4 units/day)
-AST or ALT elevation (>2.5x upper limit)
-Contraindication to MR scanning (i.e. pacemaker, metallic foreign body, claustrophobia)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL56045.018.15 |