Effect of canagliflozin, a sodium–glucose cotransporter 2 inhibitor, on measurement of serum 1,5‐anhydroglucitol (坎格列净，一种钠‐葡萄糖共转运体2抑制剂，对血清1,5‐脱水葡萄糖醇测定的影响)

Serum levels of 1,5-anhydroglucitol (1,5-AG) can be used as a measure of glycemic control in patients with diabetes. 1,5-anhydroglucitol is a non-metabolizable glucose analog that competes with glucose for renal reabsorption. In individuals with hyperglycemia, excess plasma glucose that enters the urine prevents renal reabsorption of 1,5-AG, leading to decreased serum 1,5-AG levels. Serum levels of 1,5-AG are determined using an enzymatic assay (GlycoMark; GlycoMark Inc., New York, NY, USA). This test provides a measure of glycemic control on a shorter time scale than measurement of HbA1c levels (1,5-AG reflects changes in plasma glucose over ∼2 weeks vs 8–10 weeks for HbA1c). Measurement of 1,5-AG levels has been used to evaluate the metabolic effects of several antihyperglycemic agents (AHAs); specifically, levels of serum 1,5-AG have been shown to increase when patients with type 2 diabetes mellitus (T2DM) are treated with metformin, glimepiride, or pioglitazone. Potential interference with the results of the 1,5-AG assay (GlycoMark®) has been reported for sodium– glucose cotransporter (SGLT) 2 inhibitors, a new class of AHAs developed for the treatment of patients with T2DM. The SGLT2 inhibitors decrease plasma glucose in patients with hyperglycemia by inhibiting renal glucose reabsorption via SGLT2 (the primary renal transporter responsible for reabsorption of glucose from the urine), thereby increasing urinary glucose excretion. 1,5-anhydroglucitol is transported by SGLT4, but there are no known interactions between 1,5-AG and SGLT2. Interference with the 1,5-AG assay by SGLT2 inhibitors may lead to falsely low serum 1,5-AG measurements in patients with improved glycemic control who are treated with this class of agent. Canagliflozin is an SGLT2 inhibitor approved in the US and by the European Union for the treatment of patients with T2DM. The efficacy of canagliflozin in improving glycemic control, as measured by reductions in HbA1c and fasting and postprandial plasma glucose (FPG and PPG, respectively), and the overall safety and tolerability profile of canagliflozin in patients with T2DM have been reported previously. Herein we report findings from a post hoc analysis of 1,5-AG levels using archived samples from a subset of patients who participated in a randomized, double-blind, placebocontrolled, Phase 3 study of canagliflozin monotherapy in patients with T2DM. Detailed methods from the Phase 3 study of canagliflozin monotherapy have been reported elsewhere. Archived samples (which met manufacturer specifications for storage, namely <3 years at –70°C) from 20 patients each from the canagliflozin 300 mg and placebo treatment groups of that study were included in the present post hoc analysis; this sample size was determined based on an estimate of absolute changes in serum 1,5-AG levels. Archived samples were randomly selected from a pool of samples stored in a central laboratory (Covance, Geneva, Switzerland), from patients with matching baseline and post-baseline (Week 26) samples. In patients included in the present analysis, baseline HbA1c ranged from 6.6% to 9.1%. All patients in the present study provided written informed consent prior to participation. The study was conducted in accordance with guidelines of Good Clinical Practices and the Declaration of Helsinki, and the protocol and amendments were approved by review boards at participating institutions. The GlycoMark® 1,5-AG assay was performed according to manufacturer specifications. Change from Correspondence Dainius A. Balis, Janssen Research & Development, LLC, 920 Route 202 South, Raritan, NJ 08869, USA. Tel.: +1 908 704 5173 Fax: +1 908 927 7977 Email: dbalis@its.jnj.com