Baxter International Inc. : Baxter's Low Glucose PD Solutions Favorably Impacted Metabolic Measures Including Glycemic Control in Trials of Diabetics Undergoing Dialysis

Treatment Regimen May Reduce Cardiovascular Risk Factors in Diabetic Renal Patients

Baxter International Inc. (NYSE: BAX) today announced results from two large, international multicenter trials demonstrating that a low glucose peritoneal dialysis (PD) regimen favorably impacted metabolic measures important for end-stage renal disease (ESRD) patients with diabetes, including blood glucose (sugar) control and selected lipids (fats and cholesterol). The combined results were presented as a late-breaking presentation at the 49^th Annual European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) congress in Paris.

Results from the combined IMPENDIA/EDEN trials showed that a low-glucose PD regimen led to clinically and statistically significant reductions in serum levels of HbA1c (the standard marker for assessing blood glucose control) in adult PD patients with diabetes. In the studies, significant reductions also were seen with certain lipid parameters including serum triglycerides (type of lipid or fat found in the blood), VLDL-cholesterol and apolipoprotein B (a protein that helps form LDL, or bad cholesterol, in blood) following a low-glucose PD regimen.

"A low-glucose prescription should be considered when managing diabetic patients on peritoneal dialysis," said Joanne Bargman, MD, University Health Network and professor of Medicine at the University of Toronto and presenting study investigator. "The data demonstrate low glucose PD regimens may be beneficial in aiding the management of glucose and lipid levels in diabetic PD patients."

Diabetes accounts for 25 to 50 percent of all new cases of ESRD in the majority of developed countries.^{1, 2, 3} As ESRD patients are at increased risk for cardiovascular disease, reducing the risk is an important focus, particularly in the treatment of patients with diabetes. As part of their standard dialysis therapy, PD patients are exposed to high levels of glucose.

About the Studies

The IMPENDIA and EDEN trials are randomized controlled studies involving 251 PD patients from 55 sites across 11 countries and four continents designed to evaluate the effects of a low glucose PD regimen on metabolic control over a six-month period. Combining both studies, the IMPENDIA/EDEN trials randomized 124 patients to a low glucose PD regimen containing either PHYSIONEAL (glucose), EXTRANEAL (icodextrin 7.5%), and NUTRINEAL (PD4 1.1% amino acids) in combination or a DIANEAL (PD4 glucose solution), EXTRANEAL and NUTRINEAL combination regimen versus a control group of 127 patients receiving DIANEAL-only. The primary endpoint was change in baseline of HbA1c levels between the intervention group and the control group. Secondary endpoints included evaluations of changes in serum lipids. The study protocol called for a combined analysis of the two studies.

Results showed a statistically significant reduction in the primary endpoint, as the mean HbA1c decreased by 0.5 percent in the intervention group but remained unchanged in the control group. For serum triglycerides, the difference between the low glucose and control groups represented a decrease of 0.7mmol/L. The difference for VLDL-cholesterol favoring the low glucose group was a decrease of 0.3mmol/L. These results also were statistically significant (p<0.05 level).

While an increased number of serious adverse events were observed in the intervention group, this difference was driven by two out of 17 study sites within the EDEN trial. Further analysis revealed that in the IMPENDIA trial, adverse event rates were similar between the control and intervention study arms. No overall differences between treatment groups were seen across the other 15 EDEN sites. Additional analyses are being conducted to further understand these differences.

Peritoneal Dialysis and Diabetes

ESRD is on the rise, in part due to the increasing rates of diabetes worldwide.⁴ HbA1c is a widely used marker of blood glucose control in diabetes management and higher levels in patients with diabetes indicate inadequate control of blood glucose levels, which can lead to cardiovascular disease,⁵ the leading cause of death in patients with ESRD.⁶

Peritoneal dialysis is a self-administered therapy that can be managed by patients at home and can offer a number of clinical benefits. In PD, dialysis solution is administered into the peritoneal (abdominal) cavity through a catheter in the patient's abdomen.

However, large amounts of glucose can be absorbed from conventional dialysis regimens further challenging glucose control and achievement of target blood glucose levels in PD patients with diabetes.

Together with other risk factors, such as adverse changes in blood lipids and increased incidence of metabolic syndrome (the clustering of metabolic risk factors), overall cardiovascular risk can increase in these patients. Low glucose therapy is designed to help patients reduce glucose load and exposure to decrease the risk of developing co-morbidities associated with elevated glucose, like cardiovascular disease and diabetic complications.

"These data add to the growing body of clinical evidence for Baxter's PD solutions and are an example of our ongoing efforts to seek innovative therapeutic solutions that can help improve patient outcomes," said Sarah Prichard, MD, vice president and therapeutic area lead for Baxter's Renal franchise.

About Baxter's PD Solutions

Name			Indication			Contraindication
PHYSIONEAL (glucose) solution for peritoneal dialysis			PHYSIONEAL is indicated whenever peritoneal dialysis is employed, including: acute and chronic renal failure; severe water retention; severe electrolyte imbalance; drug intoxication with dialysable substances, when a more adequate therapeutic alternative is not available. PHYSIONEAL bicarbonate/lactate based peritoneal dialysis solutions, with a physiological pH, are particularly indicated in patients in whom solutions based on a lactate buffer only, with a low pH, cause abdominal inflow pain or discomfort.			PHYSIONEAL should not be used in patients with uncorrectable mechanical defects that prevent effective PD or increase the risk of infection or with documented loss of peritoneal function or extensive adhesions that compromise peritoneal function.
EXTRANEAL (icodextrin 7.5%) solution for peritoneal dialysis			EXTRANEAL is recommended as a once daily replacement for a single glucose exchange as part of a continuous ambulatory peritoneal dialysis (CAPD) or automated peritoneal dialysis (APD) regimen for the treatment of chronic renal failure, particularly for patients who have lost ultrafiltration on glucose solutions, because it can extend time on CAPD therapy in such patients.			EXTRANEAL should not be used in patients with: a known allergy to starch based polymers/or icodextrin; maltose or isomaltose intolerance; glycogen storage disease; pre-existing severe lactic acidocis; uncorrectable mechanical defects that prevent effective PD or increase the risk of infection; documented loss of peritoneal function or extensive adhesions that compromise peritoneal function
NUTRINEAL (PD4 1.1% amino acids) solution for peritoneal dialysis			NUTRINEAL is recommended as a non-glucose based peritoneal dialysis solution as part of a peritoneal dialysis regimen for the treatment of chronic renal failure patients. In particular, it is recommended for the malnourished peritoneal dialysis patients.			NUTRINEAL should not be used in patients with hypersensitivity to any amino acids in the product or to any of the excipients; in patients with serum urea level above 38 mmol/L, in cases of uraemic symptoms, metabolic acidosis, inborn errors of amino acid metabolism, liver insufficiency and severe hypokalaemia; uncorrectable mechanical defects that prevent effective PD or increase the risk of infection; documented loss of peritoneal function or extensive adhesions that compromise peritoneal function.
DIANEAL (PD4 glucose) solution for peritoneal dialysis			DIANEAL PD4 is indicated whenever peritoneal dialysis is employed, including: acute and chronic renal failure; severe water retention; electrolyte disorders; drug intoxication, when a more adequate therapeutic alternative is not available. DIANEAL PD4 is particularly useful for the control of serum calcium and phosphate levels in renal failure patients receiving calcium or magnesium-containing phosphate binders.			DIANEAL is contraindicated in patients with: pre-existing severe lactic acidosis, uncorrectable mechanical defects that prevent effective PD or increase the risk of infection, documented loss of peritoneal function or extensive adhesions that compromise peritoneal function.

These limited summaries of product characteristics are intended for international use. Refer to country-specific Summary of Product Characteristics or package insert.

PHYSIONEAL and NUTRINEAL are not commercially available in the United States.

About Baxter

Baxter International Inc., through its subsidiaries, develops, manufactures and markets products that save and sustain the lives of people with hemophilia, immune disorders, infectious diseases, kidney disease, trauma, and other chronic and acute medical conditions. As a global, diversified healthcare company, Baxter applies a unique combination of expertise in medical devices, pharmaceuticals and biotechnology to create products that advance patient care worldwide.

Baxter, Dianeal, Extraneal, Nutrineal and Physioneal are trademarks of Baxter International Inc.

¹ USRDS Annual Data Report 2011

² ANZDATA Registry: ANZDATA Annual Report 2010

³ ERA-EDTA Registry: ERA-EDTA Registry Annual Report 2009

⁴ Diabetes in America. 2nd edition. National Diabetes Data Group. Bethesda, MD, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, (NIH publ. No. 95-468; 1995:349-400)

⁵ Larsen ML, Horder M, Mogensen EF (1990). "Effect of long-term monitoring of glycosylated hemoglobin levels in insulin-dependent diabetes mellitus". N. Engl. J. Med. 323 (15): 1021-5.

⁶ McCullough PA. Coronary artery disease. Clin J Am Soc Nephrol. 2007 May 2(3):611-6. Epub 2007 Mar 21.

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