Sodium Glucose Co-Transporter 2 Inhibition Does Not Favorably Modify the Physiological Responses to Dietary Counselling in Diabetes-Free, Sedentary Overweight and Obese Adult Humans

Abstract

Sedentary obesity is associated with increased risk of many cardio-metabolic diseases, including type 2 diabetes. Weight loss is therefore a desirable goal for sedentary adults with obesity. Weight loss is also a well-documented side effect of sodium glucose co-transporter 2 (SGLT2) inhibition, a pharmaceutical strategy for diabetes treatment. We hypothesized that, compared with placebo, SGLT2 inhibition as an adjunct to out-patient dietary counselling for weight loss would lead to more favorable modification of body mass and composition, and greater improvement in glucose regulation and lipid profile. Using a randomized, double-blind, repeated measures parallel design, 50 sedentary men and women (body mass index: 33.4 ± 4.7 kg/m2; mean ± SD) were assigned to 12 weeks of dietary counselling, supplemented with daily ingestion of either a placebo or SGLT2 inhibitor (dapagliflozin: up to 10 mg/day). Dietary counselling favorably modified body mass, body fat, glucose regulation, and fasting concentrations of triglyceride and very low-density lipoprotein cholesterol (main effects of counselling: p < 0.05); SGLT2 inhibition did not influence any of these adaptations (counselling × medication interactions: p > 0.05). However, SGLT2 inhibition when combined with dietary counselling led to greater loss of fat-free mass (counselling × medication interaction: p = 0.047) and attenuated the rise in high-density lipoprotein cholesterol (counselling × medication interaction: p = 0.028). In light of these data and the health implications of decreased fat-free mass, we recommend careful consideration before implementing SGLT2 inhibition as an adjunct to dietary counselling for weight loss in sedentary adults with obesity.

Comparison of Five Oral Cannabidiol Preparations in Adult Humans: Pharmacokinetics, Body Composition, and Heart Rate Variability

“…Participant screening comprised completion of a detailed medical history questionnaire and assessment of body size and composition using a physician's digital scale and dual energy X-ray absorptiometry (Hologic, Discovery W, QDR Series, Bedford, MA, USA) as previously described [42].…”

Sodium‐glucose co‐transporter 2 inhibitors on weight change and cardiometabolic profiles in individuals with overweight or obesity and without diabetes: A meta‐analysis

“…Pooled analysis of all eligible studies with a total of 705 participants showed that treatments with SGLT‐2 inhibitors resulted in a statistically significant reduction in body weight relative with placebos (MD = −1.31 kg, 95% CI = −1.89 to −0.72, p < 0.0001, I 2 = 0%; Figure 3A). 22–29 A statistically significant reduction in body mass index (BMI; MD = −0.47 kg/m 2 , 95% CI = −0.67 to −0.26, p < 0.0001; I 2 = 0%) was also observed when SGLT‐2 inhibitors was compared with placebo (Figure 3B). Only two studies reported the number of subjects with at least 5% weight reduction at the end of study 22,25 .…”

“…However, subjects that received SGLT‐2 inhibitors did not have statistically significant high odds in achieving a weight reduction of 5% or more (OR = 1.55, 95% CI = 0.74–3.23, p = 0.24, I 2 = 25%; Figure 3C). Data on waist circumference were reported in six studies including 474 participants 22–24,27–29 . SGLT‐2 inhibitor did not lead to a statistically significant reduction in waist circumference, compared with placebo (MD = −1.76 cm, 95% CI = −3.62 to 0.09, p = 0.06, I 2 = 0%; Figure 3D).…”

“…A total of 926 articles were retrieved from initial search. After title and abstract screening, 33 manuscripts were screened in full text, and eight randomized controlled trials with 750 participants with overweight or obesity and without diabetes (excluding subjects in intervention groups irrelevant to the review) were included in the meta‐analysis 22–29 …”

“…The study characteristics of the eight placebo‐controlled randomized controlled trials are summarized in Table 1. Five trials evaluated dapagliflozin, 23,24,27–29 two evaluated canagliflozin, 22,25 and one evaluated empagliflozin 26 . All included studies were placebo‐controlled.…”