Diabetes Research and Clinical Practice - Volume 120 - Supplement 1

PD-83

Efficacy of canagliflozin (CANA) in combination with

metformin (MET) in patients with T2DM: Results from

3 studies

Rong QIU

, John XIE

, Gill HAMILTON

William CANOVATCHEL

, Mayuresh FEGADE

Janssen

Research & Development, LLC, Raritan, NJ, United States of America;

Janssen-Cilag Ltd, High Wycombe, United Kingdom;

Janssen

Medical Affairs, Mumbai, India

Objective:

In the AACE clinical practice guidelines, SGLT2

inhibitors, such as CANA, are the first oral medication

recommended for patients inadequately controlled on MET.

This analysis assessed the efficacy of CANA in patients with

T2DM in combination with MET in 3 studies.

Methods:

Changes in A1C, body weight (BW), and systolic

blood pressure (SBP) were assessed in 3 randomized, double-

blind, Phase 3 studies of CANA in combination with MET.

CANA 100 and 300 mg were assessed vs placebo (PBO) at Week

26 and sitagliptin 100 mg (SITA) at Week 52 in Study 1

(N = 1,284), and vs glimepiride (GLIM) at Weeks 52 and 104 in

Study 2 (N = 1,450). In Study 3, drug-naïve T2DM patients (N =

1,186) received initial combination therapy with MET + CANA

100 mg (CANA100/MET) or MET + CANA 300 mg (CANA300/

MET) vs MET alone for 26 weeks.

Results:

In Study 1, CANA 100 and 300 mg significantly lowered

A1C vs PBO at Week 26; CANA 100 mg demonstrated non-

inferiority and CANA 300 mg demonstrated superiority vs SITA

at Week 52 (

–

0.73%,

–

0.88%,

–

0.73%). In Study 2, CANA 100 mg

demonstrated noninferiority and CANA 300 mg demonstrated

superiority in A1C lowering vs GLIM at Week 52; reductions

were

–

0.65%,

–

0.74%, and

–

0.55% at Week 104. In Study 3,

CANA100/MET and CANA300/MET significantly lowered

A1C vs MET at Week 26 (

–

1.77%,

–

1.78%,

–

1.30%; P = 0.001).

Significant BWreductions were seen in Study 1 with CANA 100

and 300 mg vs PBO at Week 26 and vs SITA at Week 52 (

–

3.8%,

–

4.2%,

–

1.3%; P < 0.001). In Study 2, CANA 100 and 300 mg

significantly lowered BW vs GLIM at Week 52 (

−

4.2%,

−

4.7%,

1.0%; P < 0.001); BW changes were sustained at Week 104. In

Study 3, significantly greater weight loss was seen with

CANA100/MET and CANA300/MET vs MET at Week 26 (

–

3.5%,

–

4.2%,

–

2.1%; P = 0.001). CANA 100 and 300 mg were associated

with reductions in SBP vs PBO at Week 26 and SITA at Week 52

in Study 1, and vs GLIM at Week 52 and Week 104 in Study 2. In

Study 3, SBP reductions were

–

2.2,

–

1.7, and

–

0.3 mmHg with

CANA100/MET, CANA300/MET, andMET at Week 26. CANAwas

generally well tolerated in each study, with increased inci-

dence of adverse events related to SGLT2 inhibition (e.g.,

genital mycotic infections) and low rates of hypoglycemia.

Conclusion:

In 3 studies, CANA in combination with MET

improved A1C, BW, and SBP, suggesting that a fixed-dose

combination of CANA + MET may be beneficial in patients

with T2DM.

PD-84

Real-world 12-month outcomes of patients with type 2

diabetes mellitus (T2DM) treated with canagliflozin in a US

managed care setting

Wing CHOW

, Erin BUYSMAN

, Marcia RUPNOW

Amy ANDERSON

, Henry HENK

, Mayuresh FEGADE

Janssen

Scientific Affairs, LLC, Raritan, NJ,

Optum, Eden Prairie, MN, United

States of America;

Janssen Medical Affairs, Mumbai, India

Canagliflozin (CANA), the first approved agent that inhibits

sodium glucose co-transporter 2, improves glycemic control

through an insulin-independent mechanism. This study

evaluates glycemic control pre- and post-CANA over a 12

month period. This retrospective cohort study used data froma

large US health plan for adult commercial and Medicare

Advantage enrollees with T2DM filling CANA between April

2013 andAugust 2014who hadA1C results pre andpost the first

observed CANA prescription and a pre-CANA A1C

≥

7.0%. Of

identified patients (n = 2,269), 61% had CANA 100 mg on the

first observed fill, 41%were female, andmean agewas 56 years.

Pre-CANA mean A1C was 8.93% ± 1.56%. Patients, on average,

used 2.4 ± 1.1 unique antihyperglycemic agents (AHAs) in the

pre-CANAperiod, inclusive of injectables. Basedon the last A1C

result

≥

30 days following the first observed CANA claim in the

12-month post-CANA period, patients had amean reduction of

0.96% ± 1.56%, with an average time to post-CANA A1C of 262

days. At baseline about 31% patients had mean A1C between

7%and 8%. The proportion of patients achieving A1C <7.0%and

<8.0% were approximately 25% and 59% post-CANA. The

proportion of patients with mean A1C more than 8% reduced

to 41% in post-CANA period from 69% at baseline. CANA was

prescribed to patients with T2DMwhowere often uncontrolled

(mean pre-CANA A1C of 8.93%) despite prior treatment with

multiple AHAs. Improvements in A1C consistent to those

found in clinical trials were observed in the 12 months

following the first CANA prescription.

PD-85

Efficacy of canagliflozin (CANA) versus dipeptidyl peptidase-4

inhibitors (DPP-4i) in patients with T2DM: Results from RCTs

and Real-World (RW) study

William CANOVATCHEL

, Sarah THAYER

, Wing CHOW

Rong QIU

, Michael DAVIES

, Mayuresh FEGADE

Janssen

Research & Development, LLC, Raritan, NJ,

Optum, Eden Prairie,

MN,

Janssen Scientific Affairs, LLC, Raritan, NJ, United States of

America;

Janssen Medical Affairs, Mumbai, India

In RCTs, CANAwas shown to be more effective than the DPP-4i

sitagliptin (SITA) in lowering glucose. RCT and RW results tend

to differ as RW studies may include a broader set of patients

with more advanced conditions; thus it is important to assess

the effects of agents in clinical practice. We compared the A1C-

lowering efficacy of CANA 100 and 300 mg versus SITA 100 mg

in 3 RCTs of patients with T2DM, and the effectiveness of

CANA (pooled data for all doses) in a retrospective RW

matched control-cohort study using US integrated claims

and laboratory data froma large population of insured patients

with T2DM (65% and 34% of patients received CANA 100 or

300 mg, respectively [1% other]). Three RCTs included in the

analysis were 12 week follow up study as add-on to metformin

(n = 184), 52 week follow up study as add-on to metformin

(n = 1079) and 52 week follow up study as add-on tometformin

+ suphonylurea (n = 739). Patients in the CANA cohort were

matched 1:1 to patients in the DPP-4i cohort using propensity

score matching that incorporated demographics and baseline

characteristics. In the RW study mean (median) duration of

follow up was 182.3 (191.0) days for DPP-4i and 184.2 (197.0)

days for CANA respectively. In RCTs with baseline A1C

∼

8.0%,

CANA 100 mg provided similar and CANA 300 mg provided

greater A1C reductions versus SITA 100 mg. In the RW study

with baseline A1C

∼

9.0%, greater A1C reductions were seen

with CANA (

−

1.07%) versus DPP-4i (

−

0.79%). In summary, the

relative magnitude of A1C reduction with CANA and SITAwas

similar in the RCT and RW studies; CANA consistently lowered

A1C versus DPP-4i in patients with T2DM.

PD-87

Real-world evaluation of weight loss in patients with T2DM

treated with canagliflozin (CANA)

–

An electronic health-

record (EHR)-based study

Patrick LEFEBVRE

, Wing CHOW

, Dominic PILON

Bruno EMOND

, Marie-Hélène LAFEUILLE

, Michael PFEIFER

Marcia RUPNOW

, Mei Sheng DUH

, Mayuresh FEGADE

Groupe d

’

Analyse, Ltée, Montréal, Québec, Canada;

Janssen

Scientific Affairs, LLC, Raritan, New Jersey,

Analysis Group, Inc.,

Boston, MA, United States of America;

Janssen Medical Affairs,

Mumbai, India

Objectives:

Weight management remains a challenging goal

for most patients with T2DM. However, CANA has been shown

Poster Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S65

–

S211

S118