Empagliflozin Breaks into Type 2 Diabetes Market

Boston—“[Type 2 diabetes is an] expensive and challenging disease state to treat,” said Ron Dasher, RPh, at the AMCP meeting during a product theater covering the recent approval of empagliflozin. The event was sponsored by empagliflozin’s manufacturer, Boehringer Ingelheim Pharmaceuticals, Inc., and Lilly USA, LLC. The drug was approved for the treatment of type 2 diabetes as an adjunct to diet and exercise to improve glycemic control. Empagliflozin is not recommended for patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.  

Empagliflozin is a sodium-glucose cotransporter-2 (SGLT-2) inhibitor that improves glycemic control by increasing urinary glucose excretion. SGLT-2 is the predominant transporter responsible for reabsorption of glucose from the glomerular filtrate back into the circulation. The recommended dose of empagliflozin is 10 mg, though patients who tolerate the 10 mg dose can be titrated to 25 mg. Both doses are taken orally once daily with or without food.

Empagliflozin is contraindicated for patients with a serious history of hypersensitivity. Patients with severe renal impairment, end-state renal disease, or those on dialysis are not recommended for treatment with empagliflozin.

Before initiating empagliflozin, clinicians should assess and correct volume status in patients with renal impairment, older adults, patients with low systolic blood pressure (SBP), and patients on diuretics. Hypotension should be monitored in this patient population.

Clinical study findings showed that empagliflozin, both alone and in combination across a range of background treatments, including metformin, sulfonylurea, pioglitazone, and insulin, demonstrated statistically significant reductions in hemoglobin A1c (HbA1c) and significant reductions in body weight from baseline.

During the product theater, Mr. Dasher highlighted study findings on empagliflozin therapy as a monotherapy and in combination with other diabetes medications.

Monotherapy
A total of 986 treatment-naïve patients with type 2 diabetes mellitus participated in a double-blind, placebo-controlled, 24-week study to evaluate the efficacy and safety of empagliflozin monotherapy. Patients were randomized to receive placebo, empagliflozin 10 mg, empagliflozin 25 mg, or a reference comparator.

Empagliflozin as a monotherapy significantly reduced HbA1c versus placebo and reduced body weight and SBP from baseline. At week 24, empagliflozin reduced HbA1c from a baseline mean of 7.9%. For the 10 mg and 25 mg doses, the adjusted mean reductions from baseline were −0.7% and −0.8%, respectively. An HbA1c value <7% was achieved by 12%, 35%, and 44% of patients treated with placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively. In addition, empagliflozin reduced mean SBP from baseline. For the 10 mg and 25 mg doses, the adjusted mean reductions from baseline in SBP were −2.9 mm Hg (P=.0231) and −3.7 mm Hg (P=.0028), respectively. For the 10 mg and 25 mg doses, the placebo-corrected reductions in SBP were −2.6 mm Hg and −3.4 mm Hg, respectively.

Add-On Therapy
Three studies assessed the safety and efficacy of empagliflozin as an add-on therapy to metformin, metformin plus a sulfonylurea, and insulin with or without metformin and/or a sulfonylurea.

A total of 637 patients with type 2 diabetes participated in a 24-week, double-blind, placebo-controlled study to evaluate the efficacy and safety of empagliflozin in combination with metformin. Patients with type 2 diabetes who were inadequately controlled on at least 1500 mg of metformin per day and who had an HbA1c between 7% and 10% were randomized to receive placebo, empagliflozin 10 mg, or empagliflozin 25 mg. At week 24, empagliflozin plus metformin reduced HbA1c from a mean baseline of 7.9%. Treatment with empagliflozin combined with metformin also significantly reduced SBP with placebo by −4.1 mm Hg  for 10 mg (placebo-corrected, P<.0001) and −4.8 mm Hg for 25 mg (placebo-corrected, P<.0001).
In another study, a total of 666 patients with type 2 diabetes participated in a double-blind, placebo-controlled, 24-week study to evaluate the efficacy and safety of empagliflozin in combination with metformin plus a sulfonylurea.
Patients with inadequately controlled type 2 diabetes on at least 1500 mg per day of metformin and on a sulfonylurea and those with an HbA1c between 7% and 10% were randomized to receive placebo, empagliflozin 10 mg, or empagliflozin
25 mg.

Empagliflozin reduced HbA1c from a mean baseline of 8.1%. Empagliflozin also reduced body weight from mean baseline values of approximately 168 lbs to 172 lbs.

In the final study, a total of 494 patients with type 2 diabetes participated in a double-blind, placebo-controlled study lasting 78 weeks to evaluate the efficacy and safety of empagliflozin as an add-on therapy to insulin. Patients entered a 2-week placebo run-in period on basal insulin, with or without metformin and/or sulfonylurea background therapy. Patients with inadequate glycemic control were randomized to receive the addition of empagliflozin 10 mg, empagliflozin 25 mg, or placebo. After 18 weeks of therapy, empagliflozin reduced HbA1c from a mean baseline of 8.3%. In addition, empagliflozin reduced body weight from mean baseline values ranging from approximately 198 lbs to 209 lbs.

Mr. Dasher noted that the use of a low-dose insulin or insulin secretagogue may be required to reduce the risk of hypoglycemia when used in combination with empagliflozin.

In terms of adverse events, the most common adverse reactions (>5%) associated with placebo and empagliflozin 10 mg and 25 mg were urinary tract infections (UTI; 7.6%, 9.3%, 7.6%, respectively) and female genital mycotic infections (1.5%, 5.4%, 6.4%, respectively). Mr. Dasher said people with diabetes are “predisposed to UTIs anyway.” In addition, when empagliflozin was administered with insulin or a sulfonylurea, the incidence of hypoglycemic events was increased.—Kerri Fitzgerald