Mechanisms of Weight Loss With SGLT2 Inhibition

The purpose of this study is to investigate the effect of canagliflozin, a medication approved by the FDA for the treatment of type 2 diabetes, on body weight and metabolism in people with type 2 diabetes who are overweight or obese. Canagliflozin lowers glucose levels in the blood by making the kidneys excrete, rather than absorb, glucose. Canagliflozin is also often associated with weight loss. The study population will generally be type 2 diabetics, ages 18-75 years old, who are overweight or obese.

Canagliflozin, Obesity, Weight Loss, Body Weight, Body Weight Changes, Overweight, Sodium-glucose transporter subtype 2 inhibitor

Subjects will be randomized (1:1) to treatment with canagliflozin 300mg or placebo once daily for 18 weeks.

Subjects will be randomized (1:1) to treatment with canagliflozin 300mg or placebo once daily for 18 weeks.

Subjects will take one 300mg capsule of canagliflozin or identically dispensed placebo by mouth once daily, for 18 weeks.

Subjects will take one 300mg capsule of canagliflozin or identically dispensed placebo by mouth once daily, for 18 weeks.

Body weight will be measured at each study visit (screening visit, enrollment (study week 0), and at study weeks 2, 4, 8, 12 and 18). Change in body weight will be calculated using ANOVA such that body weight at all time points is included in the data analysis, rather than simply comparing weight at the enrollment visit to weight at the final study visit.

Resting energy expenditure will be measured at each study visit using indirect calorimetery. Data analysis will include change in REE from baseline to study conclusion, as well as change in REE throughout the study.

Inclusion Criteria: Type 2 diabetes BMI 25-45 kg/m2 Hemoglobin A1C > 6.5% but < 9% Normal renal function (GFR > 60) Age 18-75 Exclusion Criteria: Type 1 diabetes History of recurrent UTI or mycotic genital infections Treatment with insulin or a GLP1 agent Pregnant or breastfeeding