Abstract

The aims of this multicentric retrospective study were to assess in a real-world setting the effectiveness and safety of canagliflozin 100 mg/d (CANA100) as an add-on to the background antihyperglycemic therapy, and to evaluate the intensification of prior sodium–glucose co-transporter type 2 inhibitor (SGLT-2i) therapy by switching to canagliflozin 300 mg/d (CANA300) in patients with T2DM. One cohort of SGLT2i-naïve patients with T2DM who were initiated on CANA100 and a second cohort of patients with prior background SGLT-2i therapy who switched to CANA300 were included in the study. The primary outcome of the study was the mean change in HbA1c over the follow-up time. In total, 583 patients were included—279 in the cohort of CANA100 (HbA1c 8.05%, weight 94.9 kg) and 304 in the cohort of CANA300 (HbA1c 7.51%, weight 92.0 kg). Median follow-up periods in both cohorts were 9.1 and 15.4 months respectively. CANA100 was associated to significant reductions in HbA1c (−0.90%) and weight (−4.1 kg) at the end of the follow-up. In those patients with baseline HbA1c > 8% (mean 9.25%), CANA100 lowered HbA1c levels by 1.51%. In the second cohort, patients switching to CANA300 experienced a significant decrease in HbA1c (−0.35%) and weight (−2.1 kg). In those patients with baseline HbA1c > 8% (mean 8.94%), CANA300 lowered HbA1c levels by 1.12%. There were significant improvements in blood pressure in both cohorts. No unexpected adverse events were reported. In summary, CANA100 (as an add-on therapy) and CANA300 (switching from prior SGLT-2i therapy) significantly improved several cardiometabolic parameters in patients with T2DM.

Highlights

  • Sodium–glucose co-transporter type 2 inhibitors (SGLT-2is) are a class of antihyperglycemic drugs that reduce tubular reabsorption of filtered glucose, inducing urinary glucose excretion (UGE) [1]

  • Greater reductions in HbA1c and blood pressure (BP) were seen among those patients receiving canagliflozin who had higher baseline HbA1c and SBP levels, respectively

  • In the subset of patients with albuminuria >30 mg/g at V1, there was a significant decrease in albuminuria with both doses, and switching to canagliflozin 300 mg (CANA300) lowered albuminuria even in patients with normal UAE

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Summary

Introduction

Sodium–glucose co-transporter type 2 inhibitors (SGLT-2is) are a class of antihyperglycemic drugs that reduce tubular reabsorption of filtered glucose, inducing urinary glucose excretion (UGE) [1]. Blocking tubular glucose reabsorption facilitates its exchange by uric acid through human glucose transporter 9 (GLUT-9), inducing uricosuria and reduction of uricemia. Unlike other SGLT2-is, which show a high specificity for SGLT-2, canagliflozin 300 mg (CANA300) induces a transient inhibition of the sodium–glucose co-transporter type 1 (SGLT-1) in the intestine, which reduces postprandial blood glucose and stimulates distal secretion of glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY), probably as a result of intraluminal glucose metabolism by the gut microbiome to short-chain fatty acids, which subsequently stimulates L cell secretion [4,5,6]

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