Clinical trial NCT03710460: Effect of Dapagliflozin/Metformin XR vs Monotherapies on Anthropometric Indicators in Obesity
Official title: Effect of the Administration of the Combination of Dapagliflozin Plus Metformin XR Versus Monotherapies on Anthropometric Indicators in Patients With Grade 1 Obesity.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Obesity
Keywords: Obesity
Dapagliflozin
Metformin XR
Visceral adiposity
Lead sponsor: University of Guadalajara
Sponsor class: OTHER
First posted: 2018-10-18
Enrollment: 33
Sex: ALL
Minimum age (years): 31
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Obesity has increased to alarming levels in the world. Currently it is estimated that it occurs in a third of the world's population and it is expected that by 2030, 20% of the world's adult population will suffer from obesity and 38% will be overweight, and it is important to highlight that Mexico is among the first in obesity in adults and children.

Obesity leads to the development of diseases such as diabetes mellitus type 2, dyslipidemias, metabolic syndrome, heart problems, among others.

The treatment for obesity in the first instance are changes in lifestyle, changes in diet and exercise that have shown, in most patients, have little long-term adherence. There are also drugs that promote weight loss by modifying the appetite or absorption of macronutrients.

Dapagliflozin plus metformin XR is a medicine composed with an oral antidiabetic of the group of inhibitors of SGLT2 that has shown to have significant side effects in the weight reduction and visceral adiposity in people with obesity and in patients with diabetes mellitus type 2, it is also composed with metformin which also has effects on weight loss in people with and without type 2 diabetes mellitus.

For these reasons, evaluating this compound drug in people with obesity could provide high impact information as a complement for the treatment of this condition when compared to the effects produced by monotherapies.

Detailed description: A double-blind, randomized clinical trial of three pharmacological groups in 33 patients with a diagnosis of grade 1 obesity in accordance with the World Health Organization (WHO) without treatment.

They will be assigned randomly three groups of 11 patients, each one will receive 10 mg of dapaglizflozin (Forxiga, Astra Zeneca), 1000 mg of metformin XR or 10/1000 mg of dapagliflozin plus metformin XR, one time per day before having break-fast during 12 weeks.

The body weight, body mass index (BMI), adiposity %, visceral adiposity, fat mass, lean mass, waist circunference,waist-hip index, arterial pressure, and laboratory parameters as a glucose, triglicerides, cholesterol, High density lipoprotein (c-HDL), low density lipoprotein (c-LDL), uric acid, creatinin, C reactive protein, adiponectin and interleukin 10, leptin and TNF-∝will be measures.

This protocol is already approved by the local ethics committee and written informed consent it's going to be obtained from all volunteers.

Statistical analysis will be presented through measures of central tendency and dispersion, average and deviation standard for quantitative variables; frequencies and percentages for variable qualitative. Qualitative variables will be analyzed by X2, will be used for differences inter-group Kruskal-Wallis Test and Wilcoxon Test for the within-groups differences. It will be considered statistical significance p ≤0.05.

Eligibility criteria: Inclusion Criteria:

* Diagnosed grade 1 obesity according to the WHO criteria:
* -Body Mass Index (BMI) between 30 to 34.9 kg/m²
* No pharmacological treatment for obesity
* Stable weight during the last 3 months

Exclusion Criteria:

* Pregnancy or breast-feeding
* History of kidney or liver disease
* Drugs or supplements consumption with proven properties that modify the behavior of obesity
* Total cholesterol \>240 mg/dL
* Triglycerides \>500mg/dL
* Glucose ≥126 mg/dL or HbA1C ≥6.5%.
* Patients who smoke daily for the last 6 months
* Hypersensitivity to dapagliflozin or metformin XR

Primary outcomes:
measure: Body Weight
timeFrame: Baseline to week 12
measure: Body Mass Index
timeFrame: Baseline to week 12
measure: Adiposity percentage
timeFrame: Baseline, week 4, week 8 and week 12
measure: Visceral adiposity
timeFrame: Baseline to week 12
measure: Lean mass
timeFrame: Baseline to week 12
measure: Fat mass
timeFrame: Baseline to week 12
measure: Waist circumference
timeFrame: Baseline to week 12
measure: Waist-hip ratio
timeFrame: Baseline to week 12
Secondary outcomes:
measure: Interleukin 10 levels IL-10
timeFrame: Baseline and week 12
measure: Adiponectin levels.
timeFrame: Baseline and week 12
measure: C-reactive protein levels
timeFrame: Baseline and week 12
measure: Leptin levels
timeFrame: Baseline and week 12
measure: TNF-α levels
timeFrame: Baseline and week 12
measure: Total cholesterol
timeFrame: Baseline to Week 12
measure: HDL cholesterol
timeFrame: Total high density lipoprotein cholesterol levels will be evaluated at baseline and week 12 by enzymatic/colorimetric techniques and the entered values reflect the high density lipoprotein cholesterol level at week 12
measure: LDL cholesterol
timeFrame: Total low density lipoprotein cholesterol levels will be evaluated at baseline and week 12 by enzymatic/colorimetric techniques and the entered values reflect the low density lipoprotein cholesterol level at week 12
measure: Triglycerides levels
timeFrame: Baseline to Week 12
measure: Fasting glucose levels
timeFrame: Baseline to Week 12
measure: Creatinine levels
timeFrame: Baseline to Week 12
measure: Uric acid levels
timeFrame: Baseline to Week 12
measure: Systolic blood pressure
timeFrame: Baseline, week 4, week 8 and week 12
measure: Diastolic blood pressure
timeFrame: Baseline, week 4, week 8 and week 12
Other outcomes:
Locations:
city: Guadalajara
country: Mexico
facility: Instituto de Terapeútica Experimental y Clínica. Centro Universitario de Ciencias de la Salud. Universidad de Guadalajara
state: Jalisco
Study officials:
affiliation: University of Guadalajara
name: Manuel Gonzalez Ortiz, MD MSc Phd
role: PRINCIPAL_INVESTIGATOR
References: