Depomed and King Pharmaceuticals' Glumetza

Diabetes presents a growing healthconcern in the United States. An estimated18 million Americans have diabetestoday, which is a startling increase from5.8 million in 1980. Combined total anddirect costs of the disease reached $132billion in 2002. Managing diabetes appropriatelycan help to both decrease complicationsand increase quality of life.¹

The FDA has approved Glumetza, aonce-daily, extended-release formulationof metformin HCl, for the treatment oftype 2 diabetes in adults. Depomed andKing Pharmaceuticals have partnered forthe production of Glumetza, and thecompanies have released Glumetza as500-mg tablets. Glumetza will also bemarketed in Canada. Glumetza may beused alone or in combination with otheroral hypoglycemic agents.²

Pharmacology

Metformin is currently available fromvarious manufacturers in multiple formulations,including both immediate-and extended-release. A unique delivery systemmakes Glumetza different from other metformin products on the market.AcuForm technology allows Glumetza tobe slowly released over 9 hours into theupper gastrointestinal (GI) tract, allowingfor once-daily administration.

Glumetza is expected to increase patient compliance through once-dailydosing and decreased incidence of GIside effects. Up to 50% of patients using immediate-release metformin experienceGI side effects, such as diarrhea,flatulence, nausea, vomiting, and abdominaldiscomfort.^2,4,5 Although bothersome, side effectsusually dissipate after severalweeks of treatment. Side effects from immediate-releasemetformin can be minimized by beginning withan initial daily dose of 500mg and gradually titrating upward.⁵ The improved side-effectpanel of Glumetza is expected, however, to allowclinicians to treat diabetes more aggressively by prescribinghigher doses earlier in the patient's treatment.²

Clinical Trials

Depomed assessed its500-mg formulation in 2double-blind clinical trials of>1000 patients. The studies lasted 24 to48 weeks. Participants demonstratedexcellent glycemic control, as determinedby reductions in both hemoglobinA1C and fasting blood glucose.⁶

Mechanism of Action

Metformin reduces glucose levels bysuppressing gluconeogenesis in thehepatic mitochondria and increasingskeletal muscle insulin sensitivity. It hasbeen used alone and in combination withother hypoglycemic agents. Metformin'sbenefits extend past its hypoglycemiceffects; metformin therapy has also beenassociated with decreased visceral fat,improved lipid panels, and decreasedcoronary atherosclerotic disease events.⁶

Safety

Although rare, lactic acidosis is apotential side effect of metformin therapy,and its outcomes can be fatal.Absolute contraindications for metformininclude:

• Creatinine >1.5 mg/mL in men
• Creatinine >1.4 mg/mL in women
• Congestive heart failure
• Metabolic acidosis
• Intravenous contrast
• Hypoxia

Nearly all instances of metformin-associatedlactic acidosis have been inpatients with contraindications. Althoughage is not an absolute contraindication,some clinicians recommend cautioususe and careful monitoring of metforminuse in patients over 80 years of age.Additionally, alcohol consumption andexcessive acetaminophen use should beavoided during metformin therapy, asboth agents may reduce the hepaticmetabolism of lactic acid.^3,6

Dr. Holmberg is a pharmacist withPhoenix Children's Hospital, Phoenix,Ariz.

For a list of references, send a stamped,self-addressed envelope to: ReferencesDepartment, Attn. A. Rybovic, PharmacyTimes, Ascend Media Healthcare, 103 CollegeRoad East, Princeton, NJ 08540; or send an emailrequest to: arybovic@ascendmedia.com.