Studies Support Robust Real-World Efficacy, Adherence, Persistence, and Quality Measure Attainment with Canagliflozin

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Poster presentations at the American Diabetes Association Scientific Sessions compared canagliflozin, an SGLT2 inhibitor, to sitagliptin, a popular DPP-4 inhibitor, using claims data.

At the 2016 American Diabetes Association Conference in New Orleans, Louisiana, researchers presented data from 6 posters supporting the safety and efficacy of Invokana (canagliflozin) in the treatment of type 2 diabetes (T2D). These posters were among 18 presentations related to canagliflozin planned for the meeting.

These studies assessed both the efficacy of canagliflozin and the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin both in combination and individually, and reported favorable results on adherence and persistence outcome measures, rates of target metabolic parameter attainment, and delayed insulin initiation. Importantly, these results included not only clinical trial data, but also real-world efficacy assessments.

Efficacy of Canagliflozin (CANA) vs. Dipeptidyl Peptidase-4 Inhibitors (DPP-4i) in Patients with Type 2 Diabetes Mellitus (T2DM): Results from Randomized, Controlled Trials (RCTs) and a Real-World (RW) Study

In this study, researchers presented glycosylated hemoglobin (A1C) lowering efficacy of canagliflozin 100 mg and 300 mg versus sitagliptin 100 mg across 2 randomized controlled trials in patients with T2D, and confirmed these results in a real-world setting through a retrospective analysis of claims data.

In the original pivotal clinical trials for canagliflozin, patients with a baseline A1C of approximately 8% receiving canagliflozin 100 mg experienced reductions comparable to those of sitagliptin 100 mg. However, A1C-lowering efficacy with canagliflozin 300 milligrams was greater than that observed with sitagliptin 100 mg.

In the real-world retrospective case-control cohort study, using propensity score matching, investigators compared patients receiving canagliflozin with similar patients receiving DDP-4 inhibitors. Approximately two-thirds of patients (65%) received canagliflozin 100 mg, with the remaining patients receiving canagliflozin 300 mg.

Patients experienced significantly greater reductions in A1c, with canagliflozin therapy resulting in an A1C reduction of 1.07 percentage points versus 0.79 percentage points with a DPP-4 inhibitor (P = .004). Although these results were obtained in patients with higher baseline A1C (approximately 9% versus 8% in the pivotal trials), these results confirm the superiority of canagliflozin versus DPP-4 inhibitors in the real-world setting.


A1C Outcomes in Patients Treated with Canagliflozin vs. Sitagliptin in a US Health Plan

An additional real-world evidence study performed using data from a large insurance claims database also confirmed the superiority of canagliflozin over sitagliptin. In this study, researchers evaluated changes in A1C among patients aged 18 years or older who had enrolled in the health plan prior to the index date of April 1, 2013, and continued enrollment in their health plan through 9 months of follow up.

Using propensity score matching, researchers paired 1472 patients receiving canagliflozin with an equal number of patients receiving sitagliptin. This statistical method enabled researchers to compensate for differences in the population of patients using sitagliptin, who tended to be older, more often female, and more likely to have comorbidities than patients receiving canagliflozin. After matching patients by clinical characteristics, the populations assessed had comparable characteristics.

Over the study period, patients receiving canagliflozin experienced significantly (P = .004) greater reductions in A1C (0.93 percentage points) versus patients receiving sitagliptin (0.57 percentage points). These results were more pronounced in patients with a baseline A1C of 7% or greater, with the A1C reduction with canagliflozin averaging 1.08 percentage points versus 0.71 percentage points with sitagliptin (P = .01). Through this real-world study, researchers further reinforced the real-world superiority of canagliflozin to sitagliptin therapy in terms of A1C reduction.

Time Until Insulin Initiation for Canagliflozin (CANA) vs. Sitagliptin (SITA) in Dual Therapy and Triple Therapy for Type 2 Diabetes Mellitus (T2DM) in the UK

As demonstrated in a study conducted in simulated patients in the United Kingdom, the superior A1C reduction efficacy with canagliflozin may postpone the need for insulin therapy versus patients receiving sitagliptin in addition to 1 or 2 other medications. Researchers used economic modeling techniques to estimate the time to insulin initiation over 40 years of follow-up.

In this simulation, and consistent with the package insert for canagliflozin, researchers modeled the effect of initiating therapy at the 100 mg daily dose and escalating to the 300 mg daily dose in patients requiring additional glycemic control. An A1C exceeding 7.5% or a decline in kidney function parameters to values inconsistent with use of canagliflozin defined the threshold for initiation of insulin therapy.

Compared with sitagliptin, use of canagliflozin delayed insulin therapy by 0.9 years in patients receiving 1 other medication (5.7 years versus 4.8 years to initiation of insulin), and by 1.2 years in patients receiving 2 other antidiabetic agents (5.1 years versus 3.9 years to initiation of insulin). Researchers noted that delays in insulin therapy initiation may also modestly reduce the risk of patients experiencing severe hypoglycemic events. These results underline the clinical relevance of the superior efficacy of canagliflozin over sitagliptin in simulated long-term outcomes for patients with T2D.

Target Achievement and Quality Measure (QM) Attainment with Titrated Canagliflozin (CANA) in Patients with Type 2 Diabetes Mellitus (T2DM) as Add-on to Metformin (MET) + Sitagliptin (SITA)

In addition to offering improved A1C reduction efficacy versus DPP-4 inhibitors, which may delay the need for insulin therapy, canagliflozin has blood pressure-lowering effects that may help patients with T2D reach goal levels consistent with quality-of-care measures that are used to grade physician performance. Researchers performed the 26-week randomized, double-blind study in 213 patients transitioning from dual therapy to triple oral therapy.

In patients who did not achieve adequate control with metformin/sitagliptin, researchers randomized patients to receive canagliflozin or placebo. Treatment with canagliflozin started at the 100 mg daily dose, and was escalated to 300 mg daily after 6 weeks provided patients had kidney function parameters consistent with use of the higher dose, fasting blood glucose levels of 100 mg/dL or greater, and no signs of adverse events related to volume depletion in the 2 weeks after initiating the increased dose of canagliflozin. The majority of patients (85.4%) successfully transitioned to the 300 mg dose over an average titration period of 6.2 weeks.

In terms of quality measure attainment, patients receiving canagliflozin were more likely to reach an A1c <7.0%, with nearly one-third (32.3%) attaining this threshold versus 12.2% of patients receiving placebo (P = .001). Similarly, patients receiving canagliflozin attained an A1c <8.0% in more than two-thirds (70.8%) of patients versus just over one-third (39.0%) of patients receiving placebo (P <.001). Attainment of a blood pressure target <140/90 mm Hg was also significantly more likely with canagliflozin than placebo (86.5% vs 78.3%, P = .017), and a more stringent goal level of <130/80 mm Hg was also more often achieved with canagliflozin (54.2% vs 32.5%, P = .001). These results indicate improved attainment of quality measures with canagliflozin as part of a 3-drug combination.

Real-World (RW) Glycemic Control and Medication Adherence among Patients with Type 2 Diabetes Mellitus (T2DM) Initiated on Canagliflozin

In addition to efficacy results and quality measure results with canagliflozin, real-world adherence data are important to validate the acceptability of long-term use in patients with T2D.

In a study of treatment adherence, researchers evaluated medical claims of patients who initiated canagliflozin in April of 2013. Patients were required to have continuous insurance enrollment in the 12 months before and after initiating therapy. Exclusion criteria included a diagnosis of type 1 diabetes, pregnancy, gestational diabetes, or steroid-induced diabetes. Adherence measures evaluated included proportion of days covered (PDC) and medication possession ratio (MPR).

Over 12 months of follow-up 881 patients with a mean age of 55 years experienced an average A1C decline of 0.8 percentage points while using a mean of 2.3 (median 2.0) other antidiabetic therapies. For patients receiving canagliflozin, PDC averaged 71% and MPR averaged 76%. Corresponding median PDC and MPR values were higher, at 83%, and 88%, respectively. In patients receiving canagliflozin, good medication adherence (as defined by MPR and PDC measures ≥80%) was achieved in the majority of patients.

Comparative Persistence with Antihyperglycemic Agents Used to Treat Type 2 Diabetes Mellitus in the Real World

In addition to adherence, persistence with antidiabetic therapy is an important predictor of outcomes. In an analysis of persistence, researchers assessed patients receiving antidiabetic therapies from February 2014 to October 2014. Persistence was assessed in patients receiving canagliflozin, dapagliflozin, dipeptidyl peptidase-4 (DPP-4) inhibitors and the glucagon-like peptide-1 (GLP-1) receptor agonists. Of 38,083 patients receiving any of these therapies and meeting inclusion criteria, two-thirds (67%) of patients receiving canagliflozin remained persistent at 9 months compared with 46% of patients receiving dapagliflozin, 47% to 53% of patients receiving DPP-4 inhibitors, and 26% to 50% of patients receiving GLP-1 agonists. These results indicate that canagliflozin is more likely to be used consistently than other antidiabetic therapies.


Regarding these studies, Paul Burton, MD, PhD, vice president of medical affairs at Janssen stated, “These real-world findings provide valuable information for physician in identifying therapeutic options with the best potential for success, which is especially important since up to half of patients with type 2 diabetes are not at treatment goals.” Burton continued, “These findings show that use of Invokana in people with type 2 diabetes lead to reduced A1C levels and, for many, achievement of treatment goals.”