Aim: To investigate acute effects of add-on therapy with the sodium glucose co‐transporter 2 inhibitor tofogliflozin to dipeptidyl peptidase (DPP)-4 inhibitors on 24-hour glucose profile and glycemic variability evaluated by continuous glucose monitoring (CGM) in patients with type 2 diabetes. Patients and methods: We studied 17 patients with type 2 diabetes who were hospitalized for glycemic control. CGM was performed for 7 consecutive days in the last week of hospitalization. Tofogliflozin 20 mg/day was started on day 4 after initiating CGM and was administered to 10 patients receiving DPP-4 inhibitors and 7 patients not receiving DPP-4 inhibitors. We compared several CGM parameters between day 2 to 3 (ie, before treatment with tofogliflozin) and day 5 to 6 (ie, after starting treatment with tofogliflozin). Results: After starting treatment with tofogliflozin, mean 24-hour glucose and postprandial glucose after each meal were significantly decreased in both groups of patients. Time in range (ie, at a glucose level of 70-180 mg/dL) was significantly increased in both groups. The standard deviation of 24-hour glucose and mean amplitude of glycemic excursions, 2 indexes of glycemic variability, were significantly decreased in patients receiving DPP-4 inhibitors but were unchanged in those not receiving these drugs. Conclusions: Add-on therapy with tofogliflozin to DPP-4 inhibitors acutely reduces 24-hour glucose levels and improves glycemic variability in patients with type 2 diabetes.

Aim: We compared the efficacy and safety of insulin degludec/insulin aspart co-formulation (IDegAsp) twice-daily to a free combination of basal insulin degludec and GLP-1 receptor agonist liraglutide (IDeg+Lira) once-daily for patients with inadequately controlled type 2 diabetes on insulin therapy and oral antidiabetic drugs. Subjects and Methods: Eligible patients were randomly allocated at a 1:1 ratio to receive either the once-daily dual-injection of IDeg+Lira (n=24) or twice-daily single-injection of IDegAsp (n=28). The primary endpoints were: HbA1c changes over 52 weeks of treatment and the percentage of participants achieving HbA1c<7.0% at week 52. Results: After 52 weeks, HbA1c decreased by 0.3% in the IDegAsp group and by 0.7% in the IDeg+Lira group. The HbA1c reduction was greater in the IDeg+Lira group than in the IDegAsp group. 19% of patients on IDegAsp versus 40% on IDeg+Lira achieved HbA1c<7.0%. Pre-breakfast and pre-dinner blood glucose at 52 weeks were significantly lower in the IDeg+Lira group than in the IDegAsp group. The reduction in body mass index (BMI) was greater in the IDeg+Lira group than in the IDegAsp group throughout the study period. The confirmed hypoglycemia rates were 1.32 and 0.69 per patient/year of exposure to IDegAsp and IDeg+Lira, respectively. Conclusions: In patients with inadequately controlled type 2 diabetes on insulin therapy and oral antidiabetic drugs, treatment with the once-daily dual-injection of IDeg+Lira compared to the twice-daily single-injection of IDegAsp showed no significant difference in glycemic control, but with a slightly larger reduction in HbA1c at 52 weeks, and statistically superior weight loss.

An association has been reported between BP and DPP-4 inhibitors. We report three cases of DPP-4 inhibitor-associated BP, with an unfavorable course in 2 patients despite discontinuation of these drugs. Therefore, clinicians should pay close attention to the clinical course of DPP-4 inhibitor-associated BP, even after withdrawal of these drugs.