New Clinical Study Shows Patients With Type 2 Diabetes May Be Able to Tolerate Higher Doses of Metformin Using GLUMETZA

MENLO PARK and SAN DIEGO, Calif., June 28 /PRNewswire-FirstCall/ -- Depomed, Inc. (NASDAQ:DEPO) and Santarus, Inc. (NASDAQ:SNTS) today announced new data suggesting that patients previously intolerant of metformin may be able to tolerate higher doses of metformin when treated with GLUMETZA® (metformin HCl extended release tablets).  The findings [abstract #0729-P] will be presented at the 70th Scientific Sessions of the American Diabetes Association (ADA) in Orlando. GLUMETZA is a once-daily, extended release formulation of metformin, and is approved for use in adults with type 2 diabetes mellitus. It is promoted in the U.S. by Santarus.

"Clinical guidelines recommend using metformin as the first-line therapy for type 2 diabetes.  Although most patients should receive the maximum recommended daily dose of 2000 mg per day to achieve optimal glycemic control, they often cannot tolerate such dosages because of gastrointestinal (GI) side effects," said Ralph A. DeFronzo, M.D., Professor of Medicine, Chief of the Diabetes Division, University of Texas Health Sciences Center, San Antonio, who co-authored the study.  "These promising new results indicate that by using GLUMETZA, an extended-release formulation of metformin, physicians might be able to use higher doses of metformin while lowering patients' risk of dose-limiting gastrointestinal events."

In the four-week observational study, 87 patients with type 2 diabetes with a history of inability to tolerate a dose of 1000 mg or more of metformin daily were treated with GLUMETZA.  The primary endpoint of the study was comparison of the maximum tolerated dose of GLUMETZA compared to the maximum dose of the patient's previous metformin formulation.  Secondary endpoints included the proportion of patients able to tolerate a GLUMETZA dose greater than 1000 mg, and the number of patients experiencing at least one GI adverse event.  The study results indicated that patients were able to use a higher mean maximum tolerated dose compared to the maximum dose of their previous metformin formulations (1477 mg vs. 1204 mg, respectively, p<0.001).  Overall, 95.4% of patients treated with GLUMETZA tolerated at least 1000 mg daily; 43% of patients tolerated up to 2000 mg daily of GLUMETZA.  

The number of patients with at least one GI adverse event (abdominal pain, diarrhea, GI upset, and nausea) was lower with GLUMETZA than with previous metformin formulations (38% vs. 88%, respectively).  One patient discontinued GLUMETZA due to an adverse GI event.

"We believe these findings underscore the potential value of the controlled release of metformin using our patented gastric retentive technology, which may result in patients tolerating higher doses of metformin due to a lower potential for GI adverse events," said Michael Sweeney, M.D., Vice President, Research and Development of Depomed.  "We believe that by allowing patients to tolerate higher doses of metformin, GLUMETZA may play an important role in helping more patients remain on metformin therapy."

About GLUMETZA

GLUMETZA (metformin hydrochloride extended release tablets) is indicated as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes. GLUMETZA may be used concomitantly with a sulfonylurea or insulin to improve glycemic control in adults. GLUMETZA is available in 500 mg and 1000 mg tablets.

• As with all metformin products, lactic acidosis due to metformin accumulation during treatment with GLUMETZA is a rare but potentially fatal occurrence.
  • May also occur in association with a number of pathophysiologic conditions.

• The risk of lactic acidosis increases with the degree of renal dysfunction and the patient's age, especially patients greater than or equal to 80 years of age, and in those patients with congestive heart failure requiring pharmacologic management.

• The risk of lactic acidosis while on GLUMETZA therapy may be significantly decreased by initial and regular monitoring of renal and liver function; using the minimum effective dose; withholding in the presence of any condition associated with hypoxemia, dehydration, or sepsis; avoidance in patients with hepatic disease; cautioning patients against excessive alcohol intake; temporarily discontinuing prior to any intravascular radiocontrast study or surgical procedure.

• Lactic acidosis is a medical emergency requiring immediate discontinuation of GLUMETZA.
  • General supportive measures and prompt hemodialysis are recommended to correct the acidosis and remove the accumulated metformin.

GLUMETZA is contraindicated in patients with renal dysfunction, known hypersensitivity to metformin HCl or metabolic acidosis, including diabetic ketoacidosis. Use of concomitant medications that affect renal function or hemodynamic change may interfere with the disposition of metformin and should be used with caution.

Hypoglycemia does not occur in patients receiving GLUMETZA alone but could occur with deficient caloric intake or during concomitant use with other glucose-lowering agents or ethanol. Loss of glycemic control may occur when a stabilized patient is exposed to stress.

In clinical trials, the most common side effects with GLUMETZA monotherapy were diarrhea, nausea, dyspepsia, and upper abdominal pain. In a clinical trial of GLUMETZA combined with a sulfonylurea, the most common side effects included hypoglycemia, diarrhea, and nausea.

For additional information on the product, please access the prescribing information at www.glumetzaxr.com.

About Diabetes

According to the 2007 National Diabetes Fact Sheet, diabetes affects an estimated 24 million Americans and its incidence is increasing by approximately 1.6 million new cases each year in the U.S. alone.  Approximately 90 percent to 95 percent of people with diabetes suffer from type 2 diabetes.  Diabetes is the most common metabolic disease in the world and the seventh deadliest disease in the U.S.  It is the leading cause of blindness, end-stage renal disease and non-traumatic loss of limb.  Diabetes can also lead to heart disease, stroke, high blood pressure, kidney disease, and other serious conditions.  In the U.S., the public health cost of diabetes in 2007 was estimated to be $174 billion per year.  In August 2006, the American Diabetes Association and the European Association for the Study of Diabetes issued a consensus statement recommending that treatment with metformin be initiated at diagnosis along with diet and lifestyle changes in patients with type 2 diabetes.

About Depomed

Depomed, Inc. is a specialty pharmaceutical company with one product candidate through Phase 3 clinical development, another in Phase 3 clinical development, two approved products on the market and other product candidates in its early stage pipeline.  Depomed formulates its products and product candidates with its proven, proprietary Acuform® drug delivery technology, which is designed to improve existing oral medications, allowing for extended, controlled release of medications to the upper gastrointestinal tract.  Additional information about Depomed may be found on its website, www.depomed.com.

About Santarus

Santarus, Inc. is a specialty biopharmaceutical company focused on acquiring, developing and commercializing proprietary products that address the needs of patients treated by gastroenterologists, endocrinologists and other physicians.  The company's current commercial efforts are focused on ZEGERID® (omeprazole/sodium bicarbonate), which is indicated for the treatment of certain upper GI diseases and disorders, and on GLUMETZA® (metformin hydrochloride extended release tablets), which is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes.  Santarus is also developing two late-stage lower GI product candidates, budesonide MMX® and rifamycin SV MMX®, for the U.S. market.  More information about Santarus is available on the company's website at www.santarus.com.

Statements included in this press release that are not a description of historical facts are forward-looking statements. The inclusion of forward-looking statements should not be regarded as a representation by either Depomed or Santarus that any of their respective plans will be achieved. Actual results may differ materially from those set forth in this release due to the risks and uncertainties inherent in Depomed's or Santarus' businesses, including, without limitation: risks related to the promotion arrangement between Depomed and Santarus (including Santarus' ability to increase market demand and sales of GLUMETZA products; competition from other products, unexpected adverse side effects or inadequate therapeutic efficacy of GLUMETZA products; the ability of Depomed to ensure continued supply of GLUMETZA products in the U.S. market; the scope and validity of patent protection for GLUMETZA products; and the potential for termination of the promotion arrangement); and other risks detailed in Depomed's and Santarus' prior press releases and public periodic filings with the Securities and Exchange Commission.

You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement and neither Depomed nor Santarus undertakes any obligation to revise or update this news release to reflect events or circumstances after the date hereof. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.

Acuform® is a trademark of Depomed, Inc. GLUMETZA® is a trademark of Biovail Laboratories International S.r.l. licensed exclusively in the United States to Depomed, Inc. Santarus, Inc.® and ZEGERID® are registered trademarks of Santarus, Inc.  MMX® is a registered trademark of Cosmo Technologies Ltd.

SOURCE Depomed, Inc.; Santarus, Inc.