Claims Study Shows Canagliflozin Produced Better A1C Results Than DPP-4 Competitor

Researchers found patients taking canagliflozin had more improvement in A1C levels than those taking DPP-4 inhibitors, and those taking canagliflozin were more likely to achieve key thresholds recognized by Medicare and other payers.

An analysis of claims data for patients taking 1 of the newer therapies for type 2 diabetes (T2D) shows that those taking the SGLT2 inhibitor canagliflozin, marketed as Invokana, had better blood glucose control than those taking drugs from the DPP-4 inhibitor class.

SGLT2, or sodium glucose transporter-2 inhibitors, work through a unique mechanism of action that works to excrete excess glucose out of the body through the urine. Canagliflozin was the first of this class to be approved in 2013, and several competitors are now available. The drug is also available in combination therapy.

The first DPP-4, or dipeptidyl peptidase 4 inhibitor approved was sitagliptin in 2006, which is marketed as Januvia. Drugs in this class work by preventing inactivation of gastrointestinal hormones released when patients eat, thus increasing insulin secretion.

The study, published Tuesday in Current Medical Research and Opinion, involved 1439 patients with T2D, including 729 taking canagliflozin (either a 100 mg or 300 mg daily dose) and 710 taking a DPP-4 inhibitor. Most of these patients were taking sitagliptin.

“These new findings are important in light of the need to identify therapeutic options with the best potential for achieving treatment goals, especially since they are estimated to remain unmet for one-half of people with type 2 diabetes,” said Richard Aguilar, MD, a co-author on the study.

Researchers used integrated claims and lab data from the Optum Research Database, which included claims from both commercial and Medicare Advantage members. Matched cohorts were selected from adults T2D patients receiving initial treatment with canagliflozin or a DPP-4 inhibitor; eligible patients needed at least 6 months’ of continuous enrollment in the health plan prior to starting therapy, 9 months of therapy, and no evidence they had taken the drug prior to the date recorded as the first prescription.

The study examined the following: (1) the average reductions in glycated hemoglobin (A1C) between the canagliflozin group and the DPP-4 inhibitor group, and (2) the percentages of each group able to reach thresholds of <8% A1C and <7% A1C during follow-up.

The mean age of both cohorts was 56 years, 43% of each cohort was female, and 67% were white. Most of the patients had commercial insurance (86%) and were prescribed the drug by their primary care physician (68%).

Of the patients taking canagliflozin, 63.3% took the 100 mg dose and 36.2% took the 300 mg dose. Of the patients taking DPP-4 inhibitors, 53.2% took sitagliptin, 24.8% took saxagliptin, 17.8% took linagliptin, and 4.2% took alogliptin.

Other Therapies in the Baseline Period. More than 90% of the patients were already taking at least 1 anti-diabetic medication in the period before their first use of canagliflozin or a DPP-4 inhibitor; in both groups, the most frequently used therapies were metformin and sulfonylureas. Insulin was used by 30.7% of the group that took canagliflozin and 13.0% of those taking DPP-4 inhibitors. GLP-1 receptor agonists were used by 26.8% of those in the canagliflozin group and 3.1% of those in the DPP-4 inhibitor group.

Average A1C Reduction. Patients taking canagliflozin had an average A1C of 8.62% at baseline and 7.70% at the 9-month follow-up, for a 0.92% reduction. Patients taking a DPP-4 inhibitor had an average A1C of 8.57% at baseline and 7.94% at follow-up, for a reduction of 0.64% ( p < 0.001).

Achieving Targets. At follow-up, a higher share of patients taking canagliflozin achieved an A1C target of <8% (66% compared with 58.6%, p = 0.004). A higher share taking canagliflozin achieved an A1C target of <7% (35.4% compared with 29.9%, p = 0.022.) However, the authors note that the share of patients achieving A1C <7% was similar for patients taking the 100 mg dose of canagliflozin and those taking the DPP-4 inhibitors.

A comparison of canagliflozin and sitagliptin, the most common DPP-4 inhibitor in the study and canagliflozin’s major competitor in the market, found that canagliflozin patients had greater A1C reductions at follow-up (0.93% vs 0.57%, p = 0.004.)


Thayer S, Chow W, Korrer S, Aguilar R. Real-world evaluation of glycemic control among patients with type 2 diabetes mellitus treated with canagliflozin versus dipeptidyl peptidase-4 inhibitors [published online March 15, 2016]. Curr Med Res Opin. 2016; doi: 10.1185/03007995.2016.1159954.

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