U.S. FDA approves supplemental New Drug Applications to include landmark data in product labels for

The U.S. Food and Drug Administration (FDA) approved supplemental New Drug Applications for three type 2 diabetes medicines within the empagliflozin family to include data from the landmark EMPA-REG OUTCOME^® trial. The data show that empagliflozin reduced the risk for cardiovascular death compared with placebo when added to standard of care type 2 diabetes and cardiovascular medicines in adults with type 2 diabetes and established cardiovascular disease. The data have been added to the "Clinical Studies" sections of the Prescribing Information for Synjardy^® (empagliflozin/metformin hydrochloride), Synjardy^® XR (empagliflozin/metformin hydrochloride extended-release) and Glyxambi^® (empagliflozin/linagliptin) tablets, all of which are marketed by Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY). SYNJARDY, SYNJARDY XR and GLYXAMBI are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. Empagliflozin, a component of these medicines, is indicated to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease. However, the effectiveness of SYNJARDY, SYNJARDY XR and GLYXAMBI on reducing the risk of cardiovascular death in adults with type 2 diabetes and cardiovascular disease has not been established.

"The addition of these data to the SYNJARDY, SYNJARDY XR and GLYXAMBI labels will help physicians better understand the available clinical trial evidence to help their patients who have type 2 diabetes and cardiovascular disease," said Thomas Seck, M.D., vice president, Clinical Development and Medical Affairs, Primary Care, Boehringer Ingelheim Pharmaceuticals, Inc. "As part of our long-standing and continuing efforts to help adults with type 2 diabetes, we are pleased that our discussions with the FDA have resulted in these important label updates."

In EMPA-REG OUTCOME, empagliflozin significantly reduced the relative risk of the combined primary endpoint of cardiovascular death, non-fatal heart attack or non-fatal stroke by 14 percent versus placebo (HR 0.86, 95% CI: 0.74-0.99) in adults with type 2 diabetes and established cardiovascular disease; absolute risk reduction was 1.6 percent for empagliflozin versus placebo. This primary finding was driven by a significant 38 percent reduction in the relative risk of cardiovascular death (HR 0.62, 95% CI: 0.49-0.77); absolute risk reduction was 2.2 percent for patients taking empagliflozin versus placebo. There was no change in the risk of non-fatal heart attack (HR 0.87, 95% CI: 0.70-1.09) or non-fatal stroke (HR 1.24, 95% CI: 0.92-1.67). The cardiovascular benefits of empagliflozin were consistent among patient subgroups.

SYNJARDY, SYNJARDY XR and GLYXAMBI are not for the treatment of type 1 diabetes or diabetic ketoacidosis. GLYXAMBI has not been studied in patients with a history of pancreatitis, and it is unknown if using GLYXAMBI increases the risk of developing pancreatitis in these patients.

SYNJARDY and SYNJARDY XR can cause serious side effects, including lactic acidosis (a buildup of lactic acid in the blood). Metformin, one of the medicines in SYNJARDY and SYNJARDY XR, can cause lactic acidosis, a rare, but serious condition that can cause death. Lactic acidosis is a medical emergency and must be treated in a hospital. SYNJARDY XR can cause dehydration, low blood pressure and increased ketones in the blood (ketoacidosis).

Adults with type 2 diabetes should not take SYNJARDY, SYNJARDY XR or GLYXAMBI if they have severe kidney problems or are on dialysis, or if they are allergic to empagliflozin. GLYXAMBI should not be taken by patients with a history of hypersensitivity reaction to linagliptin, such as anaphylaxis, angioedema, exfoliative skin conditions, urticaria, or bronchial hyperreactivity. There have been reports of acute pancreatitis, including fatal pancreatitis, in patients taking linagliptin, a component of GLYXAMBI. Other serious side effects associated with empagliflozin use are dehydration, low blood pressure, increased ketones in the blood (ketoacidosis), serious urinary tract infection, acute kidney injury and impairment in renal function, low blood glucose when used with insulin or insulin secretagogues (e.g., sulfonylurea, a medication used to treat type 2 diabetes), vaginal yeast infections and yeast infections of the penis, and increased cholesterol.