Real-World Clinical Outcomes Associated with Canagliflozin in Patients with Type 2 Diabetes Mellitus in Spain: The Real-Wecan Study.

Juan J Gorgojo-Martínez,Jaime Wong-Cruz,Miguel Brito-Sanfiel,Manuel A Gargallo-Fernández,Teresa Antón-Bravo,Alba Galdón Sanz-Pastor

doi:10.3390/jcm9072275

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

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]

Methods

Results

Conclusion