Study finds investigational compound empagliflozin reduced blood glucose in adults with Type 2 Diabetes and impaired kidney function

Ingelheim, Germany and Indianapolis, US, 22 June 2013 - Boehringer Ingelheim and Eli Lilly and Company today announced results of a 52-week Phase III clinical trial of the investigational compound empagliflozin*, which showed statistically significant reductions in HbA1c (average blood glucose) at week 24, with the addition of empagliflozin to existing oral glucose-lowering therapy in people with Type 2 Diabetes (T2D) and mild to moderate renal impairment as measured by the estimated glomerular filtration rate (eGFR ≥60 to <90mL/min/1.73m2 and eGFR ≥30 to <60mL/min/1.73 m2).¹

Empagliflozin is a member of the sodium glucose cotransporter 2 (SGLT2) inhibitor class of drugs and is being investigated for the reduction of blood glucose levels in adults with T2D. The emerging SGLT2 inhibitor class removes excess glucose through the urine by reducing glucose reabsorption in the kidney.

Results from the study, presented at the American Diabetes Association^® (ADA) 73rd Scientific Sessions, also demonstrated a significant reduction in body weight and significant improvements in blood pressure with empagliflozin versus placebo in patients with mild to moderate renal impairment.¹

"Today, nearly half of all new cases of kidney failure are due to diabetes. The Boehringer Ingelheim and Lilly Diabetes alliance is using its collective knowledge to find new treatment options that meet the different needs of people with diabetes," said Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. "This data demonstrated the potential for empagliflozin in people with Type 2 Diabetes, including people with renal impairment".

At week 24, results of the study with empagliflozin in patients with renal impairment included:

Placebo-adjusted reductions in HbA1c of 0.52% (p<0.001) and 0.68% (p<0.001) for empagliflozin 10mg and 25mg, respectively, in patients with mild renal impairment; for empagliflozin 25mg, placebo-adjusted reductions in HbA1c of 0.42% (p<0.001) in patients with moderate renal impairment¹ 

Decrease in fasting plasma glucose (FPG) levels in patients with mild renal impairment of 13.88 mg/dL (p<0.001) and 18.08mg/dL (p<0.001) for empagliflozin 10mg and 25mg, respectively, and an increase of 5.67mg/dL for placebo; in patients with moderate renal impairment, a decrease in FPG levels of 9.26mg/dL (p<0.001) for empagliflozin 25mg and an increase of 10.16mg/dL for placebo¹ 

Loss of 1.76kg (p<0.001) and 2.33kg (p<0.001) of body weight in patients with mild renal impairment for empagliflozin 10mg and 25mg, respectively, compared with a loss of 0.33kg for placebo; loss of 0.98kg (p<0.001)in body weight in patients with moderate renal impairment for empagliflozin 25mg, compared with a loss of 0.08kg for placebo¹

Improvements in both systolic (SBP) and diastolic blood pressure (DBP) with empagliflozin versus placebo: 

• Placebo-adjusted reductions in HbA1c of 0.52% (p<0.001) and 0.68% (p<0.001) for empagliflozin 10mg and 25mg, respectively, in patients with mild renal impairment; for empagliflozin 25mg, placebo-adjusted reductions in HbA1c of 0.42% (p<0.001) in patients with moderate renal impairment¹ 
• Decrease in fasting plasma glucose (FPG) levels in patients with mild renal impairment of 13.88 mg/dL (p<0.001) and 18.08mg/dL (p<0.001) for empagliflozin 10mg and 25mg, respectively, and an increase of 5.67mg/dL for placebo; in patients with moderate renal impairment, a decrease in FPG levels of 9.26mg/dL (p<0.001) for empagliflozin 25mg and an increase of 10.16mg/dL for placebo¹ 
• Loss of 1.76kg (p<0.001) and 2.33kg (p<0.001) of body weight in patients with mild renal impairment for empagliflozin 10mg and 25mg, respectively, compared with a loss of 0.33kg for placebo; loss of 0.98kg (p<0.001)in body weight in patients with moderate renal impairment for empagliflozin 25mg, compared with a loss of 0.08kg for placebo¹
• Improvements in both systolic (SBP) and diastolic blood pressure (DBP) with empagliflozin versus placebo: 
  • SBP decreased in patients with mild renal impairment by 2.9mmHg (p=0.033) and 4.5mmHg (p=0.002) for empagliflozin 10mg and 25mg, respectively, while it increased by 0.7mmHg for placebo; SBP decreased in patients with moderate renal impairment by 3.9mmHg (p=0.001) for empagliflozin 25mg, and increased by 0.4mmHg for placebo¹ 
  • DBP decreased in patients with mild renal impairment by 1.4mmHg (p=0.006) and 2.2mmHg (p<0.001) for empagliflozin 10mg and 25mg, respectively, while it increased by 1.1 mmHg for placebo; DBP decreased in patients with moderate renal impairment by 1.7mmHg (p=0.020) for empagliflozin 25mg, and increased by 0.2mmHg for placebo.¹

In this study group of people with T2D and mild or moderate renal impairment, the percentage of people who reported adverse events at 24 weeks were: 79.6%, 75.4% and 72.7% on empagliflozin 10mg, 25mg and placebo, respectively. Common adverse events include hypoglycaemia (plasma glucose ≤70mg/dL and/ or requiring assistance – reported in  23.5% of patients on empagliflozin 10mg, 22.1% on empagliflozin 25mg and 22.9% on placebo), as well as adverse events consistent with  urinary tract infection (reported in 10.2% of patients on empagliflozin 10mg, 9.0% on empagliflozin 25mg and 8.2% on placebo) and genital infection (reported in 6.1% of patients on empagliflozin 10mg, 2.5% on empagliflozin 25mg and 1.3% on placebo).

At 52 weeks, results of the study showed placebo-adjusted reductions in HbA1c of 0.62% (p<0.001) and 0.65% (p<0.001) for empagliflozin 10mg and 25mg, respectively, in patients with mild renal impairment. In patients with moderate renal impairment, results at 52 weeks showed placebo-adjusted reductions in HbA1c of 0.44% (p<0.001) for empagliflozin 25mg. Across all randomised groups at 52 weeks, adverse events were reported by 87.8% and 83.5% of patients on empagliflozin 10mg and 25mg respectively, and 84.6% on placebo.

About the study
The 52-week randomised, double-blind, placebo-controlled trial investigated the safety and efficacy of empagliflozin as an add-on to existing therapy in people with T2D and renal impairment.¹ The primary endpoint was change from baseline in HbA1c at week 24. Exploratory endpoints included changes from baseline in FPG, weight and blood pressure at week 24.^1​

About the empagliflozin Phase III clinical trial programme
Empagliflozin is being investigated in adults with T2D in a Phase III clinical trial programme that plans to enrol more than 14,500 people. This programme comprises more than 10 multinational clinical trials, including a large cardiovascular outcomes trial.

About diabetes
An estimated 371 million people worldwide have Type 1 or Type 2 Diabetes.² Type 2 Diabetes is the most common type, accounting for an estimated 90-95% of all diabetes cases.³ Diabetes is a chronic condition that occurs when the body either does not properly produce, or use, the hormone insulin.⁴

Boehringer Ingelheim and Eli Lilly and Company​
In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an alliance in the field of diabetes that centres on three compounds representing several of the largest diabetes treatment classes. This alliance leverages the companies’ strengths as two of the world’s leading pharmaceutical companies, combining Boehringer Ingelheim’s solid track record of research-driven innovation and Lilly’s innovative research, experience, and pioneering history in diabetes. By joining forces, the companies demonstrate commitment in the care of people 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
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 140 affiliates and more than 46,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.

Social responsibility is a central element of Boehringer Ingelheim's culture. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavours.

In 2012, Boehringer Ingelheim achieved net sales of about €14.7 billion. R&D expenditure in the business area Prescription Medicines corresponds to 22.5% of its net sales.

For more information please visit www.boehringer-ingelheim.com

About Eli Lilly and Company
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organisations. Headquartered in Indianapolis, IN, Lilly provides answers – through medicines and information – for some of the world's most urgent medical needs. Additional information about Lilly is available at www.lilly.com.

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 work to meet the diverse needs of people with diabetes through research and collaboration, a broad and growing product portfolio and a continued commitment to providing real solutions – from medicines to support programs and more – to make lives better.

For more information, visit www.lillydiabetes.com.