The U.S. Food and Drug Administration has approved a type 2 diabetes treatment developed through a partnership between Indianapolis-based Eli Lilly and Co. (NYSE: LLY) and Boehringer Ingelheim Pharmaceuticals Inc. The companies say Glyxambi can help lower blood sugar in adults with the condition.

February 2, 2015

News Release

Ridgefield, Conn. and Indianapolis, Ind. -- The U.S. Food and Drug Administration (FDA) has approved Glyxambi (empagliflozin/linagliptin) tablets, from Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI) and Eli Lilly and Company (NYSE: LLY), as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes (T2D) when both empagliflozin and linagliptin are appropriate treatments.

GLYXAMBI is not recommended in patients with type 1 diabetes or for the treatment of 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.

GLYXAMBI is the first and only diabetes treatment in the U.S. to combine the dual mechanisms of action of a sodium glucose co-transporter-2 (SGLT2) inhibitor and a dipeptidyl peptidase-4 (DPP-4) inhibitor in a once-daily tablet taken in the morning. GLYXAMBI combines 10 mg or 25 mg of empagliflozin with 5 mg of linagliptin. SGLT2 inhibitors remove glucose through the urine by blocking blood glucose re-absorption in the kidney. DPP-4 inhibitors work by increasing hormones that stimulate the pancreas to produce more insulin and stimulate the liver to produce less glucose.

"Today's medical community recognizes the need to treat type 2 diabetes from multiple fronts to help patients improve glycemic control," said Paul Fonteyne, president and CEO, BIPI. "With GLYXAMBI, the dual inhibition of DPP-4 and SGLT2 — two proven targets in the treatment of type 2 diabetes — now provides U.S. physicians and patients with an option to simultaneously address multiple pathways to improve glycemic control. For patients uncontrolled on metformin, phase III trial results showed GLYXAMBI provided significantly greater reductions in blood glucose levels compared with either empagliflozin or linagliptin alone."

GLYXAMBI should not be taken by patients with severe renal impairment, end-stage renal disease or dialysis; a history of hypersensitivity reaction to linagliptin, such as anaphylaxis, angioedema, exfoliative skin conditions, urticaria, or bronchial hyperreactivity; or history of serious hypersensitivity reaction to empagliflozin. There have been postmarketing reports of acute pancreatitis, including fatal pancreatitis, in patients taking linagliptin, a component of GLYXAMBI. Take careful notice of potential signs and symptoms of pancreatitis. If pancreatitis is suspected, promptly discontinue GLYXAMBI and initiate appropriate management. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using GLYXAMBI.

"Half of people with type 2 diabetes do not achieve recommended blood sugar control, making new treatment options more important than ever," said Mike Mason, vice president, U.S., Lilly Diabetes. "The approval of GLYXAMBI gives U.S. physicians and patients a first-in-class prescription medicine to help manage this condition. The approval is also a testament to our alliance's commitment to adults living with type 2 diabetes."

About the Phase III Clinical Trial

The FDA approval was based on a phase III clinical trial that evaluated the efficacy and safety of GLYXAMBI (10/5 mg and 25/5 mg) compared with the individual components of empagliflozin (10 mg or 25 mg) or linagliptin (5 mg) in adults with T2D who were also taking high-dose metformin (mean dose 1889 mg daily). The study, which randomized 686 adults with T2D and hemoglobin A1C (a measure of average blood glucose over the past two to three months) between 7.0 and 10.5 percent, examined the change from baseline in A1C at 24 weeks.

In the study, as an add-on to metformin, GLYXAMBI showed statistically significant reductions in A1C compared with empagliflozin and linagliptin alone at 24 weeks. Starting from a mean baseline of approximately 8.0 percent, adults in this trial achieved a mean A1C of 6.9 and 6.7 percent with GLYXAMBI 10/5 mg and 25/5 mg, respectively, compared with a mean A1C of 7.3 and 7.4 percent for empagliflozin 10 mg and 25 mg, respectively, and 7.3 percent for linagliptin 5 mg.

The percentage of patients achieving an A1C less than 7 percent with GLYXAMBI 10/5 mg or 25/5 mg was 58 percent and 62 percent, respectively, compared with 28 percent, 33 percent and 36 percent for empagliflozin 10 mg, empagliflozin 25 mg and linagliptin 5 mg, respectively.

Although not approved for lowering weight, GLYXAMBI provided significant weight loss at 24 weeks compared with linagliptin alone.

GLYXAMBI 10/5 mg: average body weight reduction of 3.1 percent from an average baseline of 191 lbs

GLYXAMBI 25/5 mg: average body weight reduction of 3.4 percent from an average baseline of 187 lbs

Linagliptin 5 mg: average body weight reduction of 0.7 percent from an average baseline of 187 lbs

Through 52 weeks, the overall incidence of hypoglycemia with GLYXAMBI was 2.2 percent and 3.6 percent for GLYXAMBI 10/5 mg and 25/5 mg, respectively, and there were no cases of severe hypoglycemia reported in the trial. A lower dose of an insulin secretagogue or insulin may be required to reduce the risk of hypoglycemia when used in combination with GLYXAMBI.

Through 52 weeks, the safety profile of GLYXAMBI was demonstrated in a pooled analysis, and the most common adverse reactions were:

Urinary tract infection (UTI): 12.5 percent and 11.4 percent for GLYXAMBI 10/5 mg and 25/5 mg, respectively; through 52 weeks, no patient discontinued GLYXAMBI due to UTIs

Nasopharyngitis: 5.9 percent and 6.6 percent for GLYXAMBI 10/5 mg and 25/5 mg, respectively

Upper respiratory tract infection: 7.0 percent for GLYXAMBI 10/5 mg and 25/5 mg

What is GLYXAMBI?

GLYXAMBI is a prescription medicine that contains 2 diabetes medicines, empagliflozin and linagliptin. GLYXAMBI can be used along with diet and exercise to lower blood sugar in adults with type 2 diabetes when treatment with both empagliflozin and linagliptin is appropriate.

GLYXAMBI is not for people with type 1 diabetes or for diabetic ketoacidosis (increased ketones in the blood or urine). If you have had pancreatitis (inflammation of the pancreas) it is not known if you have a higher chance of getting pancreatitis while taking GLYXAMBI.

IMPORTANT SAFETY INFORMATION

What is the most important information I should know about GLYXAMBI?

Serious side effects can happen to people taking GLYXAMBI, including:

Inflammation of the pancreas (pancreatitis), which may be severe and lead to death. Before you start taking GLYXAMBI, tell your doctor if you have ever had pancreatitis, gallstones, a history of alcoholism, or high triglyceride levels.

Stop taking GLYXAMBI and call your doctor right away if you have pain in your stomach area (abdomen) that is severe and will not go away. The pain may be felt going from your abdomen to your back. The pain may happen with or without vomiting. These may be symptoms of pancreatitis.

Dehydration. GLYXAMBI can cause some people to have dehydration (the loss of body water and salt). Dehydration may cause you to feel dizzy, faint, light-headed, or weak, especially when you stand up. You may be at higher risk of dehydration if you have low blood pressure, take medicines to lower your blood pressure, including water pills (diuretics), are on a low salt diet, have kidney problems, or are 65 years of age or older.

Vaginal yeast infection. Women who take GLYXAMBI may get vaginal yeast infections. Talk to your doctor if you experience vaginal odor, white or yellowish vaginal discharge (discharge may be lu