Home / Therapies / SGLT-2 Therapy Center / Invokana Superior As Second Add-on to Metformin

Invokana Superior As Second Add-on to Metformin

Jul 2, 2016

New study indicates canagliflozin superior to glimepiride in lowering A1C.

Over a one-year study, glycemic control was improved and body weight and blood pressure were reduced with Invokana® (canagliflozin, Janssen) as add-on therapy to metformin in patients with type 2 diabetes, according to a presentation at AACE.

Assessment of noninferiority of Invokana to glimepiride was based on a pre-specified noninferiority margin of 0.3%. If noninferiority was shown, the protocol specified a step-down assessment of superiority on the basis of an upper bound of the 95% CI for the difference of each Invokana dose vs glimepiride of less than 0.0%. Mean daily dose=5.6 mg. Glimepiride titration up to 6 mg or 8 mg was allowed throughout the study.

  • Invokana 100 mg difference from glimepiride: –0.01% (95% CI: –0.11, 0.09)
  • Invokana 300 mg difference from glimepiride: –0.12% (95% CI: –0.22, –0.02)

Secondary endpoint at 52 weeks: Percent of patients who achieved the A1C goal of <7.0% vs glimepiride:.

  • 54% with Invokana 100 mg + metformin
  • 60% with Invokana 300 mg + metformin
  • 56% with glimepiride + metformin

In the randomized, double blind study, researchers from Janssen Scientific Affairs evaluated data from 1,450 adults (mean age, 56.2 years) with type 2 diabetes (mean HbA1c, 7.8%; mean BMI, 31 kg/m2) on background metformin randomly assigned to Invokana (100 mg or 300 mg) or glimepiride for 52 weeks to determine the effects of the treatments on metabolic syndrome components.

Participants were further diagnosed with metabolic syndrome if they met two or more of the following criteria: triglyceride levels of at least 150 mg/dL; HDL cholesterol less than 40 mg/dL for men and less than 50 mg/dL for women; waist circumference at least 102 cm for non-Asian men, at least 88 cm for non-Asian women, greater than 90 cm for Asian men and greater than 80 cm for Asian women; or a diagnosis of hypertension or BP-related criteria (systolic BP 130 mm Hg or diastolic BP 85 mm Hg). At week 52, changes from baseline in HbA1c, fasting plasma glucose, BP, waist circumference, body weight, BMI and lipid levels were evaluated.

Eighty-one percent of participants met the criteria for metabolic syndrome at baseline with the proportions similar across the treatment groups. Overall, 1,160 participants had data available to assess all metabolic syndrome criteria with 39.7% meeting three, 33.7% meeting four and 17.2% meeting five criteria.

At week 52, 1,132 participants with metabolic syndrome at baseline had data available to assess metabolic syndrome criteria; there were fewer participants with metabolic syndrome in the canagliflozin 100 mg (86.7%) and canagliflozin 300 mg (85.8%) groups compared with the glimepiride group (92.7%).

HbA1c reduction was greater with canagliflozin 300 mg (-0.9%) compared with canagliflozin 100 mg and glimepiride, which both reduced HbA1c by 0.8%.

Both canagliflozin doses resulted in reductions in fasting plasma glucose, systolic BP, diastolic BP, waist circumference, body weight and BMI compared with glimepiride.

With every positive there is usually a negative and in this case LDL cholesterol and HDL cholesterol were increased with both doses of canagliflozin compared with glimepiride. Triglyceride reduction was greater with canagliflozin 100 mg compared with glimepiride whereas levels were similar between glimepiride and canagliflozin 300 mg.

“Canagliflozin improved all components of [metabolic syndrome], including glycemic control, BP, and weight loss compared with glimepiride over 52 weeks in patients with type 2 diabetes,” said Katherine Merton, PhD, of Janssen Scientific Affairs. “These findings support the use of canagliflozin versus glimepiride in patients who had type 2 diabetes and metabolic syndrome components.”

In an editorial assessing other SGLT-2 studies, (Lancet Diabetes Endocrinol. 2014;2:678–/679), Dr. Abd A. Tahrani, from the University of Birmingham, United Kingdom, noted: “Although the difference in HbA1c in favor of the SGLT-2 inhibitors is small in Ridderstråle and colleagues’ study, it occurred in the context of less hypoglycemia…than in the glimepiride group” as well as weight loss. Other studies have shown similar reductions in HbA1c with empagliflozin and canagliflozin vs. the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin (Januvia, Merck) as an add-on to metformin monotherapy. Thus, as a class, “SGLT-2 inhibitors seem to be a useful alternative to sulfonylureas because of greater and sustainable HbA1c reductions, a low risk of hypoglycemia, increased weight loss, and a favorable effect on cardiovascular risk factors,” Dr. Tahrani wrote.

Practice Pearls:

  • Two-year results show that an SGLT-2 added to metformin outperforms the addition of a sulfonylurea.
  • Canagliflozin improved all components of metabolic syndrome, including glycemic control, BP, and weight loss compared with glimepiride over 52 weeks in patients with type 2 diabetes.
  • Using an SGLT-2 treatment for type 2 diabetes as a 2nd add-on treatment to metformin was positive.

Merton K, et al. Abstract #306. Presented at: AACE Annual Scientific and Clinical Congress; May 25-29, 2016; Orlando, Fla.:  European Association for the Study of Diabetes 2014; September 16, 2014; Vienna, Austria. Abstract 02