Elsevier

Endocrine Practice

Volume 21, Issue 12, December 2015, Pages 1315-1322
Endocrine Practice

Original Articles
SGLT-2 Inhibitor Therapy Added to GLP-1 Agonist Therapy in the Management of T2DM

https://doi.org/10.4158/EP15877.ORGet rights and content

ABSTRACT

Objective: To assess the real-world efficacy and safety of canagliflozin therapy added to type 2 diabetes mellitus (T2DM) patients who have received a minimum 1 year of glucagon-like peptide-1 (GLP-1) agonist therapy.

Methods: This pre-post observational study assessed the efficacy and safety of canagliflozin in a group of T2DM patients from a community endocrinology practice who received GLP-1 agonist therapy for a minimum of 12 months. The primary study outcome was change in mean glycated hemoglobin (HbA1c) level from baseline. Secondary endpoints included changes in average weight, and comparison of the percentage of patients obtaining an HbA1c <7%.

Results: A total of 75 patients met all the study criteria. Baseline patient characteristics were as follows: average age, 58 ± 9 years; mean duration of T2DM, 14 ± 6 years; 56% male; 92% Caucasian; baseline body mass index (BMI), 39.4 ± 9.4 kg/m2; and mean baseline HbA1c, 7.94 ± 0.69%. HbA1c and weight were significantly reduced by 0.39% and 4.6 kg, respectively. Adverse effects were reported by 13 (17.3%) patients, including 4 (5.3%) who discontinued canagliflozin because of adverse reactions.

Conclusion: Canagliflozin was generally well tolerated and significantly further reduced mean HbA1c levels and body weight in patients with T2DM when added to GLP-1 regimen.

Abbreviations:

BP = blood pressure

BUN = blood urea nitrogen

CANTATA = Canagliflozin Treatment and Trial Analysis

DBP = diastolic blood pressure

DKA = diabetic ketoacidosis

DPP-4 = dipeptidyl peptidase-4

EMR = electronic medical record

FDA = Food and Drug Administration

GFR = glomerular filtration rate

GLP-1 = glucagon-like peptide-1

HbA1c = glycated hemoglobin

HDL-C = high-density lipoprotein cholesterol

LDL-C = low-density lipoprotein cholesterol

SCr = serum creatinine

SGLT-2 = sodium glucose cotransporter 2

T2DM = type 2 diabetes mellitus

TZD = thiazolidinedione

UTI = urinary tract infection

Section snippets

INTRODUCTION

It is estimated that nearly 30 million people in the Unites States, or about 10% of the population, have diabetes (1). Type 2 diabetes mellitus (T2DM) is a heterogeneous and progressive disease that accounts for more than 90% of all diabetes cases. Good glycemic control is associated with a decreased incidence of diabetes-related microvascular and potentially macrovascular complications (2). However, just over half (52.5%) of people with diabetes achieve the American Diabetes

METHODS

This pre-post observational study assessed the efficacy and safety of canagliflozin in a group of T2DM patients from a community endocrinology practice who had received GLP-1 agonist therapy for a minimum of 12 months. The protocol was reviewed and approved by the Albany College of Pharmacy and Health Sciences Institutional Review Board. Potential subjects were identified via a computerized text search of the medication and problem fields of patient electronic medical records (EMRs). Search

RESULTS

The computerized text search of the EMR identified 260 possible study candidates. Of these, 122 patients were excluded because they were not on GLP-1 therapy for at least 12 months or had switched medications in the previous 12 months, 29 patients had an HbA1c <7% or >10%, 19 patients did not have follow-up data, 9 patients were not receiving study drug or were in a clinical trial with the study drug, and 6 patients were excluded for T1DM.

A total of 75 patients met all study criteria.

DISCUSSION

This is the first reported observational study regarding the real-world safety and efficacy of the SGLT-2 inhibitor canagliflozin added to GLP-1 agonist therapy in patients with T2DM. Patients in this study demonstrated significantly reduced HbA1c, weight, and SBP and DBP and a significant increase in mean HDL-C levels with the addition of canagliflozin to baseline GLP-1 therapy.

This study reports a significant yet modest decrease in mean HbA1c of 0.39% with the addition of canagliflozin to

CONCLUSION

In this pre-post observational study, canagliflozin added to GLP-1 therapy was associated with significant reductions in HbA1c and weight, and a significant increase in mean HDL-C levels. Canagliflozin was generally well tolerated with an adverse effect profile consistent with that reported in controlled clinical trials. Overall, canagliflozin appears to be a useful therapeutic add-on to GLP-1 therapy in T2DM patients who are inadequately controlled, allowing for further HbA1c reduction and

DISCLOSURE

Dr. Robert S. Busch, is a member of the Janssen Speakers Bureau, manufacturers of canagliflozin. The other authors have no multiplicity of interest to disclose.

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