Empagliflozin effective as monotherapy for type 2 diabetes

By MD Will Boggs

NEW YORK (Reuters Health) - Empagliflozin is effective as monotherapy in patients with previously untreated type 2 diabetes, according to results from a placebo-controlled phase 3 trial.

"Empagliflozin is as effective as sitagliptin, which represents the DPP4 inhibitor class, for improving glucose control with overall tolerability as first-line oral diabetes treatment in type 2 diabetes," Dr. Michael Roden from Heinrich-Heine University in Dusseldorf, Germany, told Reuters Health by email. "Of note, empagliflozin was shown to be efficient also in patients with very bad metabolic control."

Empagliflozin is an oral, potent, selective inhibitor of sodium-glucose co-transporter 2 (SGLT2). In earlier phase 2 trials, empagliflozin was effective as monotherapy or as add-on to metformin in improving glycemic control in type 2 diabetes, Dr. Roden and colleagues note in The Lancet Diabetes & Endocrinology, online September 9.

The researchers compared the efficacy and tolerability of empagliflozin (10 mg or 25 mg) with that of sitagliptin (100 mg) and placebo, each given once daily for 24 weeks, in 889 previously untreated patients with type 2 diabetes. An additional 87 patients participated in an open-label study of empagliflozin 25 mg daily.

Among patients whose baseline hemoglobin (Hb)A1c was at least 8.5%, reductions in HbA1c were significantly greater for patients on empagliflozin 10 mg (1.44 percentage points), empagliflozin 25 mg (1.43), and sitagliptin (1.04) than for those on placebo, in whom HbA1c increased by 0.01.

Results were similar, albeit smaller, among patients whose baseline HbA1c was lower than 8.5%: decreases of 0.49 percentage points for empagliflozin 10 mg, 0.68 for empagliflozin 25 mg, 0.61 for sitagliptin, all compared with placebo.

Fasting plasma glucose changes from baseline were significantly greater at 24 weeks with empagliflozin 10 mg and 25 mg than with sitagliptin.

Patients assigned to empagliflozin had significantly greater weight loss during the study than did patients assigned to sitagliptin, and decreases in waist circumference were greater with empagliflozin than with sitagliptin or placebo.

Systolic blood pressure declined with empagliflozin, compared with sitagliptin and placebo, but diastolic blood pressure did not differ among the treatments.

Adverse events were comparable among the treatment groups, but women treated with empagliflozin reported more events consistent with urinary tract infection (12.7%-14.6%) than did women treated with sitagliptin (8.5%) or placebo (8.6%). With so many drug classes now available, how does one choose an antidiabetic?

"Metformin (if not contraindicated) always comes first -- as stated in the joint statement by ADA and EASD and by numerous guidelines," Dr. Roden said. "For further combinations, or if metformin is not tolerated or contraindicated, then there is no general recommendation for other drug classes; thus, individualized (or personalized) treatment concepts become increasingly important."

"Sulfonylurea drugs have been used for long and are effective in lowering blood glucose, but are associated with higher risk of hypoglycemia and weight gain," he added. "DPP4 inhibitors provide for lower risk of hypoglycemia and no weight gain, but there is less experience with regard to long-term safety (although most recent studies suggest no evidence for higher rates of macrovascular complications). If weight loss is important, then GLP1 analogs are the drugs of choice, but they require subcutaneous injection and are not tolerated by all patients. Glitazones (TZD) markedly improve insulin sensitivity, but several side effects including weight gain limit their general use.

"Compared to the previously mentioned drugs, the drug class SGLT2 inhibitors offer some novel advantages," Dr. Roden concluded. "In addition to very low risk of hypoglycemia and substantial weight loss, empagliflozin also decreases fasting blood glucose and systolic blood pressure. Thus, such drugs might be useful for a broad range of patients with type 2 diabetes. Nevertheless, the higher rate of urogenital infections should be considered, and we will need more long-term studies with this novel drug class."

In a related editorial, Dr. Andre J. Scheen says the choice "between a SGLT2 inhibitor and a DPP4 inhibitor to manage hyperglycemia in type 2 diabetes is difficult; each pharmacological class has advantages and disadvantages."

"The clinical results of large, long-term, prospective placebo-controlled trials assessing cardiovascular outcomes, presently ion progress with DPP4 inhibitors and SGLT2 inhibitors will help guide clinicians further," writes Dr. Scheen of CHU Sart Tilman in Liege, Belgium.

Boehringer Ingelheim and Eli Lilly, which funded the new study, announced in March 2013 that they had submitted a new drug application for empagliflozin to the U.S. Food and Drug Administration (FDA).

Also in March, the FDA announced the approval of Janssen Pharmaceuticals' canagliflozin (Invokana), the first SGLT approved to treat type 2 diabetes.

Two of the seven authors of the report received speaker's fees or research support from Eli Lilly, and Boehringer Ingelheim employed the other five.

SOURCE: http://bit.ly/1hkS1Dm and http://bit.ly/GzDMj8

Lancet Diab Endocrinol 2013.