Jardiance® (empagliflozin) analysis reinforces established safety profile

- Analysis of 12,500 adults with type 2 diabetes from 19 studies showed amputations and fractures were not increased with Jardiance compared with placebo

13 Jun, 2017, 14:00 ET from Eli Lilly and Company from ,Boehringer Ingelheim

RIDGEFIELD, Conn., and INDIANAPOLIS, June 13, 2017 /PRNewswire/ -- An analysis of pooled safety data from 19 studies, including the EMPA-REG OUTCOME® trial, involving more than 12,500 adults with type 2 diabetes demonstrated treatment with Jardiance® (empagliflozin) tablets (10 mg or 25 mg) was well tolerated, with no imbalance in lower limb amputations or bone fractures compared with placebo, Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) announced today. The analysis was published this month in Advances in Therapy.

"This is an exciting time in the advancement of treatment options for people living with type 2 diabetes and cardiovascular disease," said Thomas Seck, M.D., vice president, Clinical Development and Medical Affairs, Primary Care, Boehringer Ingelheim Pharmaceuticals, Inc. "Boehringer Ingelheim and Lilly are committed to providing available data about the efficacy and safety of our treatment options. In this light, we are proud to share the most comprehensive analysis of the safety data for Jardiance."

Jardiance is the first and only type 2 diabetes medicine approved to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease. The landmark EMPA-REG OUTCOME trial demonstrated that Jardiance reduced the risk of cardiovascular death by 38 percent versus placebo in people with type 2 diabetes and established cardiovascular disease when added to standard of care (including glucose-lowering agents and cardiovascular drugs). The overall safety profile of Jardiance in EMPA-REG OUTCOME was consistent with that of previous studies of Jardiance and current label information.

Pooled data for this analysis, which included 15 randomized Phase I-III trials and four extension studies, were analyzed from adults with type 2 diabetes treated with placebo (N=4203), Jardiance 10 mg (N=4221) or Jardiance 25 mg (N=4196). Adverse events were assessed in people who took at least one dose of Jardiance or placebo.

The analysis demonstrated that the incidences of any adverse events, severe adverse events, serious adverse events and adverse events leading to discontinuation were no higher in adults treated with Jardiance compared with those treated with placebo. The rate of lower limb amputations was similar across treatment groups (1.1 percent in all treatment groups). In EMPA-REG OUTCOME, the proportion of people with lower limb amputations was similar in those treated with placebo (1.8 percent) and Jardiance (1.9 percent). The incidences of other events potentially related to amputations (i.e., peripheral artery obstructive disease events, diabetes foot-related events, relevant infections and wounds) were similar in the placebo and Jardiance groups.

The incidence of bone fractures was also similar across treatment groups (2.9, 2.8 and 2.5 percent in the placebo, Jardiance 10 mg and Jardiance 25 mg groups, respectively). Events consistent with genital infection occurred more frequently in participants treated with Jardiance 10 mg and 25 mg (6.1 and 6.0 percent, respectively) than placebo (1.6 percent). The incidence of events consistent with urinary tract infection was similar across treatment groups (14.5-15.1 percent).

Jardiance was not associated with an increased risk of hypoglycemia compared with placebo, except in those who were on background sulfonylurea therapy (21.9, 24.5 and 23.4 percent in the placebo, Jardiance 10 mg and Jardiance 25 mg groups, respectively).

About the EMPA-REG OUTCOME Trial (NCT01131676) EMPA-REG OUTCOME was a long-term, multicenter, randomized, double-blind, placebo-controlled trial of more than 7,000 patients from 42 countries with type 2 diabetes and established cardiovascular disease.

The study assessed the effect of Jardiance (10 mg or 25 mg once daily) added to standard of care compared with placebo added to standard of care. Standard of care was comprised of glucose-lowering agents and cardiovascular drugs (including for blood pressure and cholesterol). The primary endpoint was defined as time to first occurrence of cardiovascular death, non-fatal heart attack or non-fatal stroke.

The overall safety profile of Jardiance was consistent with that of previous trials.

What is JARDIANCE? (www.jardiance.com) JARDIANCE is a prescription medicine used along with diet and exercise to lower blood sugar in adults with type 2 diabetes.

JARDIANCE is also used to reduce the risk of cardiovascular death in adults with type 2 diabetes who have known cardiovascular disease.

JARDIANCE is not for people with type 1 diabetes or for people with diabetic ketoacidosis (increased ketones in the blood or urine).

IMPORTANT SAFETY INFORMATION

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

JARDIANCE can cause serious side effects, including:

  • Dehydration. JARDIANCE 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 a 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
    • are 65 years of age or older
  • Ketoacidosis (increased ketones in your blood or urine). Ketoacidosis is a serious condition and may need to be treated in the hospital. Ketoacidosis may lead to death. Ketoacidosis occurs in people with type 1 diabetes and can also occur in people with type 2 diabetes taking JARDIANCE, even if blood sugar is less than 250 mg/dL. Stop taking JARDIANCE and call your doctor right away if you get any of the following symptoms, and if possible, check for ketones in your urine:
    • nausea
    • vomiting
    • stomach-area (abdominal) pain
    • tiredness
    • trouble breathing
  • Serious urinary tract infections. Serious urinary tract infections can occur in people taking JARDIANCE and may lead to hospitalization. Tell your doctor if you have symptoms of a urinary tract infection such as a burning feeling when passing urine, a need to urinate often or right away, pain in the lower part of your stomach or pelvis, or blood in the urine. Sometimes people also may have a fever, back pain, nausea or vomiting.
  • Vaginal yeast infection. Women who take JARDIANCE may get vaginal yeast infections. Talk to your doctor if you experience vaginal odor, white or yellowish vaginal discharge (discharge may be lumpy or look like cottage cheese), and/or vaginal itching.
  • Yeast infection of the penis. Men who take JARDIANCE may get a yeast infection of the skin around the penis, especially uncircumcised males and those with chronic infections. Talk to your doctor if you experience redness, itching or swelling of the penis, rash of the penis, foul smelling discharge from the penis, and /or pain in the skin around penis.

Who should not take JARDIANCE? Do not take JARDIANCE if you are allergic to empagliflozin or any of the ingredients in JARDIANCE. Symptoms of serious allergic reactions to JARDIANCE may include:

  • skin rash
  • raised red patches on your skin (hives)
  • swelling of the face, lips, tongue, and throat that may cause difficulty breathing or swallowing.

If you have any of these symptoms, stop taking JARDIANCE and contact your doctor or go to the nearest emergency room right away.

Do not take JARDIANCE if you have severe kidney problems or are on dialysis.

What should I tell my doctor before using JARDIANCE?

Tell your doctor if you:

  • have kidney problems. Your doctor may do blood tests to check your kidneys before and during your treatment with JARDIANCE
  • have liver problems
  • have a history of urinary tract infections or problems with urination
  • are going to have surgery
  • are eating less due to illness, surgery, or a change in your diet
  • have or have had problems with your pancreas, including pancreatitis or surgery on your pancreas
  • drink alcohol very often, or drink a lot of alcohol in the short term ("binge" drinking)
  • have any other medical conditions
  • are pregnant or planning to become pregnant. It is unknown if JARDIANCE will harm your unborn baby
  • are breastfeeding, or plan to breastfeed. It is unknown if JARDIANCE passes into your breast milk.

Tell your doctor about all the medicines you take including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your doctor if you take water pills (diuretics) or medicines that can lower your blood sugar such as insulin.

What are other possible side effects of JARDIANCE?

  • Low blood sugar (hypoglycemia): if you take JARDIANCE with another medicine that can cause low blood sugar, such as sulfonylurea or insulin, your risk of low blood sugar is higher. The dose of your sulfonylurea or insulin may need to be lowered. Symptoms of low blood sugar may include:
    • Headache
    • Drowsiness
    • Weakness
    • Dizziness
    • Confusion
    • Irritability
    • Hunger
    • Fast heartbeat
    • Sweating
    • Shaking or feeling jittery
  • Kidney Problems. Sudden kidney injury has happened in people taking JARDIANCE. Talk to your doctor right away if you reduce the amount you eat or drink, or if you lose liquids; for example, from vomiting, diarrhea, or being in the sun too long.
  • Increased fats in your blood (cholesterol).

The most common side effects of JARDIANCE include urinary tract infections, and yeast infections in females.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

For more information, please see full Prescribing Information and Patient Information.

JAR CONS ISI 1.11.17

Boehringer Ingelheim and Eli Lilly and Company In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an alliance in diabetes that centers on compounds representing several of the largest diabetes treatment classes. This alliance leverages the strengths of two of the world's leading pharmaceutical companies. By joining forces, the companies demonstrate commitment in the care of patients with diabetes and stand together to focus on patient needs. Find out more about the alliance at www.boehringer-ingelheim.com or www.lilly.com.

About Boehringer Ingelheim Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation.

Boehringer Ingelheim is one of the world's top 20 pharmaceutical companies. Headquartered in Ingelheim, Germany, the company operates globally with approximately 50,000 employees. Since its founding in 1885, the company has remained family-owned and today creates value through innovation for three business areas including human pharmaceuticals, animal health and biopharmaceutical contract manufacturing.

Boehringer Ingelheim is committed to improving lives and providing valuable services and support to patients and their families. Our employees create and engage in programs that strengthen our communities. Please visit our website to learn more about how we make more health for more people through our Corporate Social Responsibility initiatives.

In 2016, Boehringer Ingelheim achieved net sales of about $17.6 billion (15.9 billion euros). R&D expenditure corresponds to 19.6 percent of its net sales.

For more information please visit www.boehringer-ingelheim.us, or follow us on Twitter @BoehringerUS.

About Lilly Diabetes Lilly has been a global leader in diabetes care since 1923, when we introduced the world's first commercial insulin. Today we are building upon this heritage by working to meet the diverse needs of people with diabetes and those who care for them. Through research and collaboration, a wide range of therapies and a continued determination to provide real solutions—from medicines to support programs and more—we strive to make life better for all those affected by diabetes around the world. For more information, visit www.lillydiabetes.com.

About Eli Lilly and Company Lilly is a global healthcare leader that unites caring with discovery to make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us at www.lilly.com and www.lilly.com/newsroom/social-channels.

This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about Jardiance and reflects Lilly's current belief. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of development and commercialization. Among other things, there can be no guarantee that future study results will be consistent with the results to date or that Jardiance will receive additional regulatory approvals. For further discussion of these and other risks and uncertainties, see Lilly's most recent Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.

Jardiance® and EMPA-REG OUTCOME® are registered trademarks of Boehringer Ingelheim.

P-LLY

PC-04689

CONTACT:

Lauren Murphy, MBA Associate Director, Public Relations Boehringer Ingelheim Pharmaceuticals, Inc. Email: lauren.murphy@boehringer-ingelheim.com Phone: (203) 448-1982

Grant Smith Communications Lilly Diabetes Email: grant.smith@lilly.com Phone: (317) 954-9907

SOURCE Eli Lilly and Company; Boehringer Ingelheim