Dapagliflozin and Cholesterol Metabolism in Type 2 Diabetes (DM2)

NCT03074630 | Completed Phase 4 Results

• 1 other identifier: METC AMC 2016_016
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diabetes Mellitus, Type 2; Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• Change in Plasma LDL Cholesterol

  Before and after 5 weeks of dapagliflozin on rosuvastatin background.

  5 weeks

Secondary Outcomes (12)

• Change in Plasma HDL Cholesterol

  12 weeks

• Change in Total Cholesterol

  5 weeks

• Change in Plasma Triglycerides

  5 weeks

• Change in Plasma FFA

  5 weeks

• Change in Cholesterol Fluxes

  5 weeks

Study Arms (1)

Dapagliflozin 10mg and Rosuvastatin 10mg

EXPERIMENTAL

Rosuvastatin 10mg once daily for 9 weeks, with 5 weeks of once daily Dapagliflozin 10mg added

Drug: Dapagliflozin; Drug: Rosuvastatin

Interventions

Dapagliflozin DRUG

5 weeks 10mg dapagliflozin once daily

Also known as: Forxiga

Dapagliflozin 10mg and Rosuvastatin 10mg

Rosuvastatin DRUG

9 weeks 10mg dapagliflozin once daily

Also known as: Crestor

Dapagliflozin 10mg and Rosuvastatin 10mg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or postmenopausal female patients ;
• 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
• years of age
• Ability to provide informed consent

You may not qualify if:

• 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)

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator

Study Sites (1)

Academic Medical Center

Amsterdam, North Holland, 1105AZ, Netherlands

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hypercholesterolemia

Interventions

dapagliflozin; Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

The comparatively small number of participants, the absence of a control group and short follow-up time limit the study and we only included subjects with uncomplicated type 2 diabetes on metformin monotherapy.

Results Point of Contact

• Title: Erik van Bommel
• Organization: AmsterdamUMC

e.vanbommel@amsterdamumc.nl

+31 20 4444444

Study Officials

• Max Nieuwdorp, MD/PhD

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Masking Details: Open Label
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI

Study Record Dates

• First Submitted: June 22, 2016
• First Posted: March 9, 2017
• Study Start: May 1, 2016
• Primary Completion: April 1, 2018
• Study Completion: April 1, 2018
• Last Updated: August 4, 2020
• Results First Posted: August 4, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)