Effectiveness of Dapagliflozin for Weight Loss

• Status: Recruiting
• Trial end date: 2021-07-01
• Target enrollment: 0
• Participant gender: All

Summary

Mexico has one of the highest prevalence of obesity, reported on 32.4 percent of people over 20 years old, with a prevalence of obesity class III of 1.8 percent on males and 4.1 percent on females.

According to previous data in our Obesity Clinic the mean age of these patients is 41 years, 46 percent have pre-diabetes or type 2 diabetes mellitus (T2D); 66 percent has hypertension and 33 percent has dyslipidemia. The management of alterations in the glucose metabolism in this unit is made by dietary treatment and with the use of metformin at doses of 1,700 mg/day and/or basal insulin.

Dapagliflozin is a selective SGLT2 inhibitor than has shown a sustained effect on the reduction of glycated hemoglobin at 0.4 to 0.8 percent (initial 7.8 to 8.0 percent). Additionally, due to the induction of glycosuria up to 20 to 85 g/day, it has been calculated that its use induces a caloric deficit at 80 to 340 kcal/day. This has been tested in patients with T2D in which induces a weight loss of 2 to 3 kg and in combination with metformin even a weight loss up to 5.07 kg (-6.21 to 3.93 kg) without regain (at least for 2 years). Furthermore, dapagliflozin decrease systolic blood pressure, increases HDL cholesterol concentrations and decreases triglyceride concentration. The drug product action is independent of the insulin production at pancreas, consequently, it exists a possibility of using the drug product on patients with prediabetes or even on other types of diabetes. Regarding the adverse effects related to its use, it has been described an increase in the risk of genitourinary infections with a low risk for inducing hypoglycemia.

A previous study that included 182 patients with T2D inadequately controlled with metformin assessed the effect of dapagliflozin 10 mg in total weight loss after 24 weeks compared to placebo. It was found a decrease in weight of 2.08 kg (2.8 to 1.31 kg), decrease in waist circumference of 1.52 cm (2.74 to 0.31), decrease in total fat mass assessed with densitometry of 1.48 kg (2.22 to 0.74), decrease of visceral fat mass of 258.4 cm^3 (448.1 to 68.6) and subcutaneous fat of 184.9 cm^3 (359.7 to 10.1). Most of these studies on weight and metabolic control have been performed in patients with obesity class II or I. The aim of this study is to assess if dapagliflozin in combination with metformin is at least 10 percent more effective for weight reduction in comparison with metformin in patients with prediabetes or T2D and obesity grade III.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centro Medico Nacional Siglo XXI IMSS
• Treatments: 2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol; Dapagliflozin; Metformin; Sodium-Glucose Transporter 2 Inhibitors

Criteria

Inclusion Criteria:

• BMI greater than or equal to 40 kg/m^2

• Diagnosis of diabetes or prediabetes according to the criteria of the ADA

• Patients who sign informed consent letter

Exclusion Criteria:

• Use of insulin or sulfonylureas

• Chronic renal failure with glomerular filtration rate <60 ml/min/1.73 m^2

• Use of loop diuretics with no possibility to suspend

• Active genitourinary tract infections determined by symptomatology or urinalysis

• Use of drugs for weight control

• Patients with untreated or uncontrolled hypothyroidism