Bayer Glyset (miglitol) antidiabetic is outlicensing candidate following Dec. 18 approval.

BAYER GLYSET ORAL ANTIDIABETIC WILL BE OUTLICENSED OR CO-MARKETED, Bayer said following FDA approval of the Type II diabetes treatment Dec. 18. Bayer is discussing possible international marketing agreements, the firm said. Glyset (miglitol) has been approved in the European Union under the brand name Diastabol.

Glyset, like Bayer's first alpha-glucosidase inhibitor Precose (acarbose), is indicated "as an adjunct to diet to improve glycemic control in patients with non-insulin dependent diabetes mellitus whose hyperglycemia cannot be managed with diet alone," labeling says. Bayer submitted the Glyset NDA (20-682) on Dec. 28, 1995. Precose was approved in September 1995 and launched in January ("The Pink Sheet" Sept. 11, 1995, p. 3).

Glyset and Precose have identical indications and recommended dosing regimens and similar safety profiles. The main difference between the two drugs, Bayer said, is that Glyset is systemically absorbed while Precose is not. The difference in absorption has not been proven to be clinically relevant, the company added.

Glyset is an "important option for Hispanics and African-Americans," Bayer declared. Although not mentioned in labeling, Bayer says "two large studies undertaken by Bayer have shown that Glyset is particularly effective among Hispanic and African-American Type II patients."

A pharmacodynamic response study of a single 50-mg dose in African-American and Caucasian healthy volunteers "indicated similar glucose and insulin responses in both populations," labeling states.

Bayer outlicensed the extended-release calcium channel blocker Sular (nisoldipine) to Zeneca following its approval in early 1995. In that case, Bayer already received revenues from formulations of nifedipine marketed by Pfizer as Procardia XL and Bayer as Adalat CC.

Glyset labeling includes summaries of five studies that evaluated Glyset as fixed-dose monotherapy in 735 Type II patients. The studies showed Glyset to produce a greater glycosylated hemoglobin (HbA1c) level reduction and greater reduction of postprandial plasma glucose and postprandial serum insulin levels compared to placebo. Three additional trials studied Glyset as adjunctive therapy to a background of maximal or near-maximal sulfonylurea treatment in 471 patients. Results showed Glyset to have an additive treatment effect on HbA1c levels.

Glyset may "be used in combination with a sulfonylurea when diet plus either Glyset or a sulfonylurea alone does not result in adequate glycemic control," labeling says. "The effect of Glyset to enhance glycemic control is additive to that of sulfonylureas when used in combination, presumably because its mechanism of action is different."

Glyset is recommended at a starting dosage of 25 mg three times daily taken "at the start (with the first bite) of each main meal," labeling says. Some patients may benefit by starting with 25 mg once daily and gradually increasing to three times daily "to minimize gastrointestinal adverse events." The recommended maintenance dose is 50 mg three times daily, "although some patients may benefit from increasing the dose to 100 mg three times daily," labeling adds.

"Gastrointestinal symptoms are the most common reactions to Glyset," including abdominal pain, diarrhea and flatulence, although "the incidence of diarrhea and abdominal pain tended to diminish considerably with continued treatment," labeling states. Rash was reported in 4.3% of patients on miglitol, compared to 2.4% of those taking placebo, although labeling adds that "rashes were generally transient and most were assessed as unrelated to Glyset by physician investigators."