No evidence of compensatory changes in energy balance, despite reductions in body weight and liver fat, during dapagliflozin treatment in type 2 diabetes mellitus: A randomized, double‐blind, placebo‐controlled, cross‐over trial (ENERGIZE)

Abstract

AimThis study assessed the impact of dapagliflozin on food intake, eating behaviour, energy expenditure, magnetic resonance imaging (MRI)‐determined brain response to food cues and body composition in patients with type 2 diabetes mellitus (T2D).Materials and MethodsPatients were given dapagliflozin 10 mg once daily in a randomized, double‐blind, placebo‐controlled trial with short‐term (1 week) and long‐term (12 weeks) cross‐over periods. The primary outcome was the difference in test meal food intake between long‐term dapagliflozin and placebo treatment. Secondary outcomes included short‐term differences in test meal food intake, short‐ and long‐term differences in appetite and eating rate, energy expenditure and functional MRI brain activity in relation to food images. We determined differences in glycated haemoglobin, weight, liver fat (by 1H magnetic resonance spectroscopy) and subcutaneous/visceral adipose tissue volumes (by MRI).ResultsIn total, 52 patients (43% were women) were randomized; with the analysis of 49 patients: median age 58 years, weight 99.1 kg, body mass index 35 kg/m2, glycated haemoglobin 49 mmol/mol. Dapagliflozin reduced glycated haemoglobin by 9.7 mmol/mol [95% confidence interval (CI) 3.91‐16.27, p = .004], and body weight (−2.84 vs. −0.87 kg) versus placebo. There was no short‐ or long‐term difference in test meal food intake between dapagliflozin and placebo [mean difference 5.7 g (95% CI −127.9 to 139.3, p = .933); 15.8 g (95% CI −147.7 to 116.1, p = .813), respectively] nor in the rate of eating, energy expenditure, appetite, or brain responses to food cues. Liver fat (median reduction −4.7 vs. 1.95%), but not subcutaneous/visceral adipose tissue, decreased significantly with 12 weeks of dapagliflozin.ConclusionsThe reduction in body weight and liver fat with dapagliflozin was not associated with compensatory adaptations in food intake or energy expenditure.

Changes in daily intake of nutrients and foods including confectionery after the initiation of empagliflozin in Japanese patients with type 2 diabetes: a pilot study

“…However, a recent study reported that dapagliflozin treatment may not affect food intake or the brain’s response to appetite [ 11 ]. Other studies have also found no difference in dietary intake [ 11 – 14 ], and thus the evidence is inconclusive in this regard.…”

“…However, a recent study reported that dapagliflozin treatment may not affect food intake or the brain’s response to appetite [ 11 ]. Other studies have also found no difference in dietary intake [ 11 – 14 ], and thus the evidence is inconclusive in this regard. Specific changes in intake of different nutrients and food groups and how they relate to the effects of SGLT2i are also unclear.…”