In the Journals

Ipragliflozin enhances glycemic management, but fails to curb appetite

The SGLT2 inhibitor ipragliflozin can help adults with type 2 diabetes to meet glycemic and weight targets, although it may not alter feelings of hunger, according to findings presented in the Journal of Diabetes Investigation.

Kazuhiko Sakaguchi, PhD, an associate professor in the department of internal medicine, division of diabetes and endocrinology at Kobe University Graduate School of Medicine in Japan, and colleagues conducted a multicenter, open-label clinical trial by recruiting 96 adults with type 2 diabetes with HbA1c levels between 6.5% and 9.5% and a BMI of at least 22 kg/m2 (mean age, 57.2 years; 51% women) from Kobe University Hospital in Japan from April 2015 to October 2017. For 16 weeks, participants received 50 mg ipragliflozin (Astellas Pharma and Kotobuki Pharmaceutical) each day after a morning meal.

Before trial commencement, participants fasted overnight and then had HbA1c, glycated albumin and plasma glucose levels measured from blood and urine samples. These measures were taken again every 4 weeks during the trial. Additional data such as body weight and BMI were taken at baseline as well. Serum leptin and ghrelin levels were assessed at baseline and twice more in the first 4 weeks of the study before shifting to 4-week intervals. Additional testing for hunger intensity was carried out via visual analogue scale, with higher scores indicating greater appetite. These measures were taken at baseline, after the first 2 weeks of the trial and then at 8 and 16 weeks.

Mean HbA1c levels were lower after 16 weeks of ipragliflozin therapy compared with baseline measures (7.1% vs. 7.9%; P < .01). Participants also lost weight during the 16 weeks of treatment, with an average weight of 72.6 kg after the trial compared with a baseline mark of 75.2 kg (P < .01). After 16 weeks, participants had lower plasma glucose (129.1 mg/dL vs. 158.1 mg/dL; P < .01) and glycated albumin (16.4% vs. 19.2%) levels and BMI (27.7 kg/m2 vs. 28.7 kg/m2; P < .01 for all) compared with baseline.

In terms of appetite hormones, the largest decline was in serum leptin at 2 weeks compared with baseline (18.1 ng/mL vs. 19.3 ng/mL; P < .01), but the researchers noted that a decrease remained after 16 weeks (17.5 ng/mL; P = .02). However, ghrelin measures showed no statistically significant changes between baseline and 16 weeks. Furthermore, the researchers found that reported hunger was higher in the first 8 weeks of the trial based on visual analogue scores compared with baseline (45.8 mm vs. 39.9 mm; P = .04).

“The apparent return of appetite to the baseline level by 16 weeks despite a continuing reduction in the serum leptin level might have been attributable to resolution of leptin resistance as a consequence of body weight reduction,” the researchers wrote. “The study period of this trial was relatively short. A longer-term interventional trial would provide more useful information about the effect of SGLT2 inhibitor on body weight, glycemic profile, appetite and its related hormones.” – by Phil Neuffer

Disclosures: Sakaguchi reports he received lectures fees from Astellas Pharma Inc and Merck Sharp & Dohme. Please see the study for all other authors’ relevant financial disclosures.

The SGLT2 inhibitor ipragliflozin can help adults with type 2 diabetes to meet glycemic and weight targets, although it may not alter feelings of hunger, according to findings presented in the Journal of Diabetes Investigation.

Kazuhiko Sakaguchi, PhD, an associate professor in the department of internal medicine, division of diabetes and endocrinology at Kobe University Graduate School of Medicine in Japan, and colleagues conducted a multicenter, open-label clinical trial by recruiting 96 adults with type 2 diabetes with HbA1c levels between 6.5% and 9.5% and a BMI of at least 22 kg/m2 (mean age, 57.2 years; 51% women) from Kobe University Hospital in Japan from April 2015 to October 2017. For 16 weeks, participants received 50 mg ipragliflozin (Astellas Pharma and Kotobuki Pharmaceutical) each day after a morning meal.

Before trial commencement, participants fasted overnight and then had HbA1c, glycated albumin and plasma glucose levels measured from blood and urine samples. These measures were taken again every 4 weeks during the trial. Additional data such as body weight and BMI were taken at baseline as well. Serum leptin and ghrelin levels were assessed at baseline and twice more in the first 4 weeks of the study before shifting to 4-week intervals. Additional testing for hunger intensity was carried out via visual analogue scale, with higher scores indicating greater appetite. These measures were taken at baseline, after the first 2 weeks of the trial and then at 8 and 16 weeks.

Mean HbA1c levels were lower after 16 weeks of ipragliflozin therapy compared with baseline measures (7.1% vs. 7.9%; P < .01). Participants also lost weight during the 16 weeks of treatment, with an average weight of 72.6 kg after the trial compared with a baseline mark of 75.2 kg (P < .01). After 16 weeks, participants had lower plasma glucose (129.1 mg/dL vs. 158.1 mg/dL; P < .01) and glycated albumin (16.4% vs. 19.2%) levels and BMI (27.7 kg/m2 vs. 28.7 kg/m2; P < .01 for all) compared with baseline.

In terms of appetite hormones, the largest decline was in serum leptin at 2 weeks compared with baseline (18.1 ng/mL vs. 19.3 ng/mL; P < .01), but the researchers noted that a decrease remained after 16 weeks (17.5 ng/mL; P = .02). However, ghrelin measures showed no statistically significant changes between baseline and 16 weeks. Furthermore, the researchers found that reported hunger was higher in the first 8 weeks of the trial based on visual analogue scores compared with baseline (45.8 mm vs. 39.9 mm; P = .04).

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“The apparent return of appetite to the baseline level by 16 weeks despite a continuing reduction in the serum leptin level might have been attributable to resolution of leptin resistance as a consequence of body weight reduction,” the researchers wrote. “The study period of this trial was relatively short. A longer-term interventional trial would provide more useful information about the effect of SGLT2 inhibitor on body weight, glycemic profile, appetite and its related hormones.” – by Phil Neuffer

Disclosures: Sakaguchi reports he received lectures fees from Astellas Pharma Inc and Merck Sharp & Dohme. Please see the study for all other authors’ relevant financial disclosures.