Sodium–glucose cotransporter 2 inhibitor, tofogliflozin, shows better improvements of blood glucose and insulin secretion in patients with high insulin levels at baseline

Abstract

Aims/IntroductionSodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of drugs for the treatment of type 2 diabetes mellitus that improve control of plasma glucose and bodyweight, giving great hope for the clinical utility of these agents. However, it is unclear for which patients SGLT2 inhibitors will be useful.Materials and MethodsWe analyzed data from long‐term tofogliflozin monotherapy in an open‐label, randomized controlled trial in Japanese patients with type 2 diabetes mellitus. Patients were divided into tertiles by baseline insulin level: group low (L): insulin ≤5.6 μU/mL, group medium (M): 5.6< insulin ≤10 μU/mL and group high (H): insulin >10 μU/mL.ResultsGlycated hemoglobin and fasting plasma glucose levels, along with bodyweight, were significantly reduced from the baseline in all groups. The changes in levels of plasma glucose area under the curve for 2 h, C‐peptide index area under the curve for 2 h during the meal tolerance tests and the insulin secretion index were the largest in the H group. The incidence of drug‐related adverse events was not different among the three groups.DiscussionAlthough tofogliflozin was effective regardless of baseline insulin level, it showed the highest efficacy in the H group.

Efficacy of sodium-glucose cotransporter 2 inhibitor with glucagon-like peptide-1 receptor agonist for the glycemic control of a patient with Prader-Willi syndrome: a case report

“…Although insulin secretion is known to be induced by GLP-1 receptor agonists, it may be enhanced by SGLT2 inhibitors, possibly through different mechanisms, including the attenuation of glucotoxicity and improvement of insulin resistance. It has been reported that a SGLT2 inhibitor, tofogliflozin, increases insulin secretion especially in patients with high insulin levels at the baseline, suggesting that SGLT2 inhibitors may facilitate the recovery of β-cell dysfunction when the insulin secretion capacity is preserved to a certain extent (16). Consistently, both insulin resistance and secretion were improved in our patient.…”

Impact of body mass index on the efficacy and safety of ipragliflozin in Japanese patients with type 2 diabetes mellitus: A subgroup analysis of 3‐month interim results from the Specified Drug Use Results Survey of Ipragliflozin Treatment in Type 2 Diabetic Patients: Long‐term Use study

“…The results of the present subgroup analysis are consistent with what is observed in clinical practice, in that a significant reduction in HbA1c was shown with ipragliflozin treatment in patients with BMI ≥30 kg/m 2 . Although we did not identify a strong correlation between bodyweight reduction and improvement in HbA1c in the present study, such a correlation has been reported previously for another SGLT2 inhibitor, tofogliflozin. In that study, patients were divided into tertiles according to baseline insulin levels, and a correlation between improvement in glucose control and reduction in bodyweight was observed, but only in the tertile with the highest fasting insulin level.…”

Should sulfonylurea be discontinued or maintained at the lowest dose when starting ipragliflozin? A multicenter observational study in Japanese patients with type 2 diabetes

“…In fact, HDL-C is one of the components for classification of metabolic syndrome. Similarly, beneficial effects on glycemic control have been observed with higher BMI compared with lower BMI in Japanese phase III trials of SGLT2is 23,24 . Similarly, beneficial effects on glycemic control have been observed with higher BMI compared with lower BMI in Japanese phase III trials of SGLT2is 23,24 .…”

“…In the present study, HDL-C and BMI in the Discontinuation group were significantly negatively correlated (r = -0.27, P < 0.05; Figure 3b). Similarly, beneficial effects on glycemic control have been observed with higher BMI compared with lower BMI in Japanese phase III trials of SGLT2is 23,24 . An additional glucoselowering effect due to the improvement in insulin resistance or sensitivity is expected to be larger when SGLT2 inhibitors are administered in patients with higher BMI.…”