Invokana superior to glimepiride for glycemic control, weight loss, BP

Over 52 weeks, glycemic control was improved and body weight and blood pressure were reduced with Invokana as add-on therapy to metformin in patients with type 2 diabetes, according to a presentation here.

In the randomized, double blind study, Katherine Merton, PhD, of Janssen Scientific Affairs, and colleagues 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 (canagliflozin, Janssen) 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 cangliflozin 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.

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 Merton said. “These findings support the use of canagliflozin versus glimepiride in patients who had type 2 diabetes and metabolic syndrome compnents.” – by Amber Cox

Canagliflozin: Drug Safety Communication – New Information on Bone Fracture Risk and Decreased Bone Mineral Density

ISSUE: FDA has strengthened the warning for the type 2 diabetes medicine canagliflozin (Invokana, Invokamet) related to the increased risk of bone fractures, and added new information about decreased bone mineral density. To address these safety concerns, FDA added a new WARNING AND PRECAUTION and revised the ADVERSE REACTIONS section of the Invokana and Invokamet drug labels.

FDA is continuing to evaluate the risk of bone fractures with other drugs in the SGLT2 inhibitor class, including dapagliflozin (Farxiga, Xigduo XR) and empaglifozin (Jardiance, Glyxambi, Synjardy), to determine if additional label changes or studies are needed. Health care professionals and patients are urged to report side effects involving canagliflozin or other SGLT2 inhibitors to the FDA MedWatch program.

RECOMMENDATIONS: Health care professionals should consider factors that contribute to fracture risk prior to starting patients on canagliflozin. Patients should talk to their health care professionals about factors that may increase their risk for bone fracture. Patients should not stop or change their diabetes medicines without first talking to their health care professional. Additional information for Health Care Professionals:

  • Bone fractures have been seen in patients taking the type 2 diabetes medicine canagliflozin.
    • Fractures can occur as early as 12 weeks after starting canagliflozin.
    • Canagliflozin has also been linked to decreases in bone mineral density at the hip and lower spine.
    • Consider factors that contribute to fracture risk prior to initiating canagliflozin.
    • Counsel patients about factors that may contribute to bone fracture risk.





Phase 3 study: Canagliflozin improved beta cell function.

An SGLT2 inhibitor recently approved by the FDA may improve measures of beta cell function in addition to glycemic control in patients already taking metformin plus sulfonylurea, according to phase 3 study results presented here at the AACE Annual Scientific and Clinical Congress.

“Despite the fact it doesn’t act directly on the beta cells, there is a lot of evidence from previous studies that SGLT2 inhibitors can improve beta-cell function,” David Polidori, PhD, of Janssen Research & Development, LLC, said here during a presentation.

Polidori and colleagues conducted a 26-week, randomized, double blind, placebo controlled study to evaluate canagliflozin (Invokana, Janssen) 100-mg and 300-mg compared with placebo as an add on to metformin plus sulfonylurea in patients with type 2 diabetes (n=469; mean age, 57 years). The mean baseline HbA1c level was 8.1%, BMI was 33 kg/m2, and duration of diabetes was 9.6 years, according to data.

Of the 469 patients, 168 were administered a meal tolerance test at baseline and week 26. Their plasma glucose and serum C-peptide levels were measured seven times over a 3-hour period.

Polidori reported that at week 26, canagliflozin 100 mg significantly reduced HbA1c by –0.71% and 300 mg  by –0.92% compared with placebo (P<.001).

Further data indicate that the insulin secretion rates (ISR) vs. glucose relationship did not change with placebo. However, the relationship shifted upwards in both canagliflozin doses, Polidori said. This indicated an increase in ISR at each plasma glucose concentration, according to data.

Measures of beta cell function, including the ratio of C-peptide to glucose, were approximately 20% higher than baseline levels in both canagliflozin groups (P=.051 for 100 mg and P=.056 for 300 mg) but remained relatively unchanged in the placebo group. Mean beta cell glucose sensitivity was also increased by about 20% in both canagliflozin groups (P=.14 for 100 mg andP=.22 for 300 mg).

Additionally, mean ISR at 9 mM of glucose increased by about 50% to 60% in both canagliflozin groups (P=.02 for 100 mg and P=.007 for 300 mg), but remained relatively unchanged in the placebo group.

“Consistent with what we’ve seen in patients at earlier stages of diabetes and in some of the animal studies, both doses of canagliflozin improved the measures of beta cell function that we looked at in the meal tolerance test in these more advanced patients who were already inadequately controlled on dual therapy. This is promising,” Polidori said. “This is 26-week data and we’re certainly interested to see longer term data to see if this type of treatment can better prolong beta cell function and hopefully slow the rate of progression of type 2 diabetes.” – by Samantha Costa

Source: Endocrine Today



FDA Approves Novel Diabetes Drug.

The FDA has approved the first oral inhibitor of sodium glucose cotransporter 2 (SGLT2) to treat adults with type 2 diabetes. Canagliflozin (Invokana) lowers blood sugar by blocking the kidneys’ urinary reabsorption of glucose, resulting in increased urinary excretion.

In nine studies comprising over 10,000 patients, the SGLT2 inhibitor improved hemoglobin A1c levels and blood sugar levels. Canagliflozin has been studied as a stand-alone treatment and in combination with metformin, sulfonylurea, pioglitazone, and insulin.

Common side effects include urinary tract infection and vaginal yeast infection. Dizziness or fainting could occur during the first 3 months of treatment due to the tablet’s diuretic effect, which can lead to orthostatic or postural hypotension. The drug should not be used in patients with type 1 diabetes, diabetic ketoacidosis, severe renal impairment, or end stage renal disease.

Source: FDA news