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.