EASD: Positive Results for Two SGLT2 Inhibitors

And in another study of a renal sodium-glucose co-transporter-2 (SGLT2) inhibitor, researchers found similar positive results.

Atsunori Kashiwagi, MD, director of medical affairs at Shiga University of Medical Science, in his oral presentation stated that, in the BRIGHTEN study, patients treated with ipragliflozin achieved a mean decrease of 1.23% in glycosylated hemoglobin A1c (HbA1c) compared with placebo (P<0.001).

In addition, "fasting plasma glucose was reduced by 45.8 mg/dL compared with placebo and body weight was decreased by 1.47 kg compared with placebo -- both significant findings at P<0.001."

For the BRIGHTEN double-blind randomized study, researchers assigned 62 patients to ipragliflozin and 67 to placebo. Overall, about 60% of participants were men, mean age was 59, and the mean body mass index was 25 kg/m² -- considerably leaner than participants in type 2 diabetes trials in Western cultures, Kashiwagi said. Those with type 2 diabetes had been diagnosed for about seven years.

Patients were recruited during a 14-week period, which included a four-week screening period, followed by a two-week placebo run-in, and washout period in which they discontinued anti-diabetic treatments. Patients were given 50 mg daily of the medication or placebo and followed for 16 weeks. After the treatment period, the patients were followed for another four weeks.

Patients in the ipragliflozin cohort experienced a reduction of 0.76% in HbA1c, the primary endpoint, compared with 0.47% in the placebo patients -- a net difference of 1.23%, Kashiwagi reported.

• Fasting glucose declined by 40.2 mg/dL in the intervention arm compared with an increase of 6.3 mg/dL in the placebo group -- a net difference of 46.5 mg/dL (P<0.001).
• Body weight declined 2.36 kg among those on ipragliflozin compared with 0.89 kg among those on placebo -- a net decline of 1.47 kg (P<0.001).
• Systolic and diastolic blood pressure declined 3.2 mm Hg and 25 mm Hg, respectively, in the medication arm, but these changes were not significant when compared to placebo.

The treatment was well tolerated, with similar emergent adverse events occurring in about half the patients in both cohorts. The ipragliflozin group had one case of hypoglycemia and two genital tract infections, while the placebo group had one urinary tract infection.

In the other presentation investigating TS-071, another SGLT2 inhibitor, Yutaka Seino, MD, from Kyoto University, and colleagues found a linear relationship between dose and HbA1c reduction:

• 0.5 mg -- 0.43% decline
• 2.5 mg -- 0.70% decline
• 5 mg – 0.82% decline

Compared with placebo, which had no improvement in HbA1c, all differences were significant at P<005, Seino said. Mean age of patients was 58, with more than two-thirds being men. Mean HbA1c at baseline was about 8%, and body mass index about 25 kg/m2. The researchers randomized 54 patients to placebo and the rest to the investigational drug: 60, 61, and 61 to 0.5 mg, 2.5 mg, and 5 mg.

In general, treatment with TS-071 was well tolerated, but one urinary tract infection occurred at the low dose; one case of vulvitis was observed at the 2.5 mg dose; and one case of vulvovaginal candidiasis was seen in a woman taking the 5 mg dose. Pollakiuria was reported by one placebo patient and by three patients in both the 2.5 mg and 5 mg doses of TC-071.

The results show that TS-071 significantly improved HbA1c and other glycemic parameters in Japanese patients with type 2 diabetes mellitus.

Practice Pearls:

• Note that these studies were published as abstracts and were presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

• Explain that two Japanese studies of different renal sodium-glucose co-transporter-2 (SGLT2) inhibitors found the drugs decreased glycosylated hemoglobin and body weight in type 2 diabetics.

• Note that both studies also found a decrease in blood pressure among recipients of the SGLT2 inhibitors compared to placebo, but that the results were only significant for ipragliflozin and not the other drug, TS-071.

Seino Y, et al "A novel potent and highly selective renal sodium-glucose co-transporter 2 (SGLT2) inhibitor, TS-071, improves glycaemic control and lowers body weight in Japanese patients with type 2 diabetes mellitus" EASD 2011; Abstract 148 -149