Clinical data for investigational SGLT2 inhibitor, empagliflozin*, demonstrates potential for oral treatment in type 2 diabetes

Boehringer Ingelheim and Eli Lilly and Company today announced results of a pooled analysis of Phase IIb data for empagliflozin*, their investigational inhibitor of the sodium glucose co-transporter-2 (SGLT2).1

Empagliflozin* belongs to an innovative class of compounds, the SGLT2 inhibitors, and is currently being investigated for the reduction of blood glucose in patients with T2D.2 T2D is characterised by persistent hyperglycaemia (high blood glucose) along with declining beta cell function and increasing insulin resistance.3,4 Most classes of currently available oral T2D treatments depend on the actions of the hormone insulin to lower elevated blood glucose. SGLT2 inhibitors reduce glucose reabsorption in the kidney, leading to excretion of excess glucose via the urine. With a mode of action independent of insulin, SGLT2 inhibitors reduce blood glucose levels regardless of either insulin resistance or beta cell function. 2,5

The new, pooled Phase IIb data presented at the EASD Congress (PS 059 SGLT2 IV 770) examined the effect of empagliflozin* on blood pressure in addition to its primary action on HbA1c reduction and weight loss.1 Reductions in systolic blood pressure (SBP) of 4-5 mmHg from baseline were observed with empagliflozin*, with more pronounced reductions seen in patients with higher SBP (>140 mmHg at baseline).

Mean SBP at baseline of 131.3 mmHg and 132.5 mmHg were observed with empagliflozin* 10 mg and 25 mg, respectively, versus 134.3 mmHg with placebo. At week 12, reductions in mean SBP of 3.8 mmHg and 4.5 mmHg were observed with empagliflozin* 10 mg and 25 mg, respectively versus 1.2 mmHg for placebo. For both dosages the reduction from baseline in SBP was statistically significant versus placebo. In patients with higher SBP at baseline mean reductions of 17.0 mmHg and 13.4 mmHg were observed with empagliflozin* 10 mg and 25 mg, respectively, and 10.4 mmHg with placebo.

Reductions in diastolic blood pressure were greater with both empagliflozin* doses compared to placebo but did not reach statistical significance. Reductions in blood pressure were not correlated with reductions in weight or HbA1c.

Professor Michael Nauck, Head of the Diabeteszentrum Bad Lauterberg, Germany commented: “High blood pressure is an important contributor to higher cardiovascular death in people with T2D. Addressing elevated blood pressure should be an integral part of the management of T2D, together with elevated blood glucose.”

Empagliflozin* was well-tolerated with the number of patients experiencing adverse events (AEs) comparable among the different treatment groups at week 12 (34.2% on empagliflozin* 10 mg, 31.6% on empagliflozin* 25 mg and 34.6% in placebo groups).1 The most commonly observed AEs include urinary tract and genital infections, generally categorised as mild, as seen in all clinical empagliflozin* trials to date.6

Empagliflozin* is currently being investigated in the largest Phase III clinical trial programme in diabetes with over 14,500 patients planned to be enrolled. The programme includes ten multi-national Phase III clinical trials, including a large cardiovascular outcome trial. Pivotal studies could complete in late 2012, with filing planned in the U.S. and Europe by 2013.

“The Boehringer Ingelheim and Lilly Alliance is excited about the promising profile of empagliflozin. We are looking forward to additional data for empagliflozin from our ongoing Phase III programme, including effects on blood pressure and body weight in addition to lowering blood glucose in patients with T2D.” said Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim.

About Diabetes

An estimated 366 million people worldwide have diabetes.7 Type 2 diabetes is the most common type, accounting for an estimated 90% of all diabetes cases.8 Diabetes is a chronic disease that occurs when the body either does not properly produce, or use, the hormone insulin.9

References

1. Hach et al. The Sodium Glucose Cotransporter-2 (SGLT-2) Inhibitor Empagliflozin Lowers Blood Pressure Independent of Weight or HbA1c Change. Presented at the 48th European Association for the Study of Diabetes (EASD) Annual Meeting, Berlin, Germany. 2012 1-5 October 2012.
2. Grempler R, Thomas L, Eckhardt M, Himmelsbach F, Sauer A, Sharp DE, et al. Empagliflozin, a novel selective sodium glucose cotransporter-2 (SGLT-2) inhibitor: characterisation and comparison with other SGLT-2 inhibitors. Diabetes, Obesity and Metabolism. 2012;14(1):83-90.
3. Goldstein BJ. Expert column – understanding type 2 diabetes. The growing epidemic of type 2 diabetes. Medscape Diabetes & Endocrinology. 2006;14(9).
4. DeFronzo R. From the triumvirate to the ominous octet: A new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58:773-95.
5. Abdul-Ghani MA, DeFronzo R. Inhibition of renal glucose reabsorption: A novel strategy for achieving glucose control in type 2 diabetes mellitus. Endocrine Practice. 2008;14(6):782-90.
6. Woerle HJ, Ferrannini E, Berk A, Manun’Ebo M, Pinnetti S, Broedl UC. Safety and efficacy of empagliflozin as monotherapy or add-on to metformin in a 78-week open-label extension study in patients with type 2 diabetes. 72nd Scientific Sessions of the American Diabetes Association. Philadelphia, Pennsylvania, USA, June 2012.
7. International Diabetes Federation. The Global Burden. IDF Diabetes Atlas. 2011(5th Edition).
8. World Health Organization. Fact Sheet No. 312 What is Diabetes?, 2010
9. International Diabetes Federation. What is Diabetes? . IDF Diabetes Atlas. 2011(5th Edition).

*Empagliflozin is an investigational compound. Its safety and efficacy have not yet been fully established