Effects of ipragliflozin on glycemic control, appetite and its related hormones: A prospective, multicenter, open‐label study (SOAR‐KOBE Study)

Abstract

Aims/Introduction Sodium–glucose cotransporter 2 (SGLT‐2) inhibitors improve blood glucose control, as well as reducing bodyweight by promoting urinary glucose excretion. The weight loss is less than expected from urinary glucose loss, however, likely because of an increase in food intake. To investigate whether SGLT‐2 inhibitors might increase appetite by affecting related hormones, we examined the effects of the SGLT‐2 inhibitor, ipragliflozin, including those on appetite‐regulating hormones, in individuals with suboptimally controlled type 2 diabetes. Materials and Methods The present prospective, multicenter, open‐label study was carried out with 96 patients with a body mass index of ≥22 kg/m2 who were treated with ipragliflozin (50 mg/day) for 16 weeks. Parameters including glycated hemoglobin level, bodyweight, circulating leptin and active ghrelin concentrations, and appetite as assessed with a visual analog scale were measured before and during treatment. Results Both glycated hemoglobin level (from 7.9 ± 0.8 to 7.1 ± 0.7%) and bodyweight (from 75.2 ± 12.6 to 72.6 ± 12.4 kg) were significantly decreased after treatment for 16 weeks. The fasting serum leptin level was significantly decreased after 2 weeks (from 19.5 ± 13.1 to 18.1 ± 12.4 ng/mL) and remained decreased up to 16 weeks, even after adjustment for bodyweight, whereas the plasma active ghrelin level showed no significant change. The visual analog scale score for hunger was significantly increased at 2 and 8 weeks. Conclusions The present results suggest that ipragliflozin improved glycemic control and reduced bodyweight, but also reduced serum leptin levels and might thereby have increased appetite.

Mechanisms of Glucose Absorption in the Small Intestine in Health and Metabolic Diseases and Their Role in Appetite Regulation

“…For instance, inhibition of fat absorption in the gut by orlistat produced an anti-obesity effect but increased food intake [ 131 ]. Use of gliflozin in humans was also accompanied by an increased feeling of hunger and sugar intake [ 132 , 133 ]. One of the arguments for the potential utility of SGLT1 inhibition as a treatment of hyperphagia, assumes that prolonged elevated luminal levels of glucose may directly or indirectly (for example, via microbiota) activate secretion of intestinal satiety hormones, for example, PYY [ 134 ].…”

The Mechanism of Metabolic Influences on the Endogenous GLP-1 by Oral Antidiabetic Medications in Type 2 Diabetes Mellitus

“…Given that both SGLT-2 and GLP-1 are associated with weight control and food intake, Hiroshi et al investigated the effect of SGLT-2 inhibitors by evaluating the effect of 16 6 Journal of Diabetes Research weeks of ipragliflozin treatment on body weight and hormones related to appetite regulation in patients with BMI ≥ 22 kg/m 2 . The treatment led to a significant reduction in fasting serum leptin levels after two weeks, which remained the same for up to 16 weeks, whereas the plasma active ghrelin level showed no significant change [61]. The reduction of the leptin level could indicate the resolution of leptin resistance accompanied with bodyweight reduction because overweight or obesity is associated with leptin resistance.…”

SGLT2 inhibitors for genetic and acquired insulin resistance: Considerations for clinical use

“…In obese individuals, circulating leptin levels are increased as a result of impairment of leptin action (recognized as leptin resistance), which is thought to be related to the development of insulin resistance. The decrease in serum leptin levels observed in response to SGLT2 inhibitor treatment was accompanied by an increase in appetite 14 , suggesting that the decrease in the circulating leptin concentration was not attributable to amelioration of leptin resistance, rather the decrease results in a reduction in anorexigenic signaling in the hypothalamus, which is well known to be stimulated by leptin, and a consequent increase in appetite. However, a change in appetite is not always observed during treatment with SGLT2 inhibitors 15 .…”

“…Treatment with SGLT2 inhibitors results in a loss of body and fat mass 8–12,14,15 , as well as in amelioration of fatty liver 7,9 , all of which potentially contribute to an improvement in insulin resistance. Treatment with SGLT2 inhibitor has been shown to reduce serum leptin levels, even after standardization by body mass 14 .…”

“…Treatment with SGLT2 inhibitors results in a loss of body and fat mass [8][9][10][11][12]14,15 , as well as in amelioration of fatty liver 7,9 , all of which potentially contribute to an improvement in insulin resistance. Treatment with SGLT2 inhibitor has been shown to reduce serum leptin levels, even after standardization by body mass 14 . In obese individuals, circulating leptin levels are increased as a result of impairment of leptin action (recognized as leptin resistance), which is thought to be related to the development of insulin resistance.…”