Improved antilipolytic effect in adipose tissue via SGLT2i attenuates weight loss in T2D patients
Progressive lipolysis may be reduced via the improved antilipolytic effect in adipose tissue, which leads to a reduction in future weight loss caused by sodium-glucose cotransporter 2 inhibitors (SGLT2is) in patients with type 2 diabetes (T2D), suggests a recent study.
The authors analysed data from 774 patients with T2D (mean age, 58.5 years; glycosylated haemoglobin, 8.1 percent; body mass index, 25.6 kg/m2; estimated glomerular filtration rate, 83.9 mL/min/1.73m2; 66 percent men).
After decreasing significantly, weight loss plateaued between weeks 24 and 52. There was a significant decrease in fasting insulin levels from baseline to week 24, and this was maintained until week 52. Levels of fasting free fatty acids significantly increased and peaked at week 24 before decreasing at weeks 24–52.
Furthermore, levels of adipose tissue insulin resistance (Adipo-IR) decreased progressively all the way through week 52 (–3.6 and −6.2 mmol/L·pmol/L at weeks 24 and 52, respectively; p<0.001 for baseline vs weeks 24 and 52 and week 24 vs week 52). Higher baseline levels of Adipo-IR showed an independent association with greater weight loss at week 52.
This study sought to determine the mechanism of the attenuated weight loss during long-term treatment with an SGLT2i, tofogliflozin, focusing on the antilipolytic effect of insulin on adipose tissue. The authors conducted an integrated analysis using data from two phase III studies of 52 weeks of tofogliflozin administration.
Adipo-IR, calculated from the product of the levels of fasting insulin and fasting free fatty acids, was used to assess the antilipolytic effect.