Rx PRODUCT NEWS PROFILE: Byetta (exenatide)

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Pharmacy Times, Volume 0,0

Diabetes mellitus is a chronicdisease that affects 18.2 millionpeople in the UnitedStates.1 Type 2 diabetes is the most commonlydiagnosed type; it is frequentlycaused by peripheral insulin resistanceor impaired insulin secretion.2 Combinationtherapy is often necessary whena single drug fails to control plasma glucose.The FDA has approved Byetta(exenatide), manufactured by AmylinPharmaceuticals Inc, as an adjunctivetherapy for the treatment of type 2 diabetesin patients who cannot achieveblood sugar control on metforminand/or sulfonylurea.3

Pharmacology

Byetta is an incretin mimetic agentthat is composed of a 39-amino acidpeptide. Incretins improve glucose-dependentinsulin secretion andinhibit glucagon release. Byetta leadsto an increase in insulin secretion, adecrease in glucagon release, adecrease in food intake, delayed gastricemptying, and an elevated beta-cellproduction.3,4

Clinical Trials

A triple-blind, placebo-controlledstudy evaluated the effectiveness oftwice-daily subcutaneous injections ofByetta (5 mcg and 10 mcg) withmatching placebo. The trial included377 patients with type 2 diabetes whohad been treated with sulfonylureamonotherapy for 3 months prior toinitiating the study therapy. Allpatients continued sulfonylurea therapythroughout the study. After 30weeks, hemoglobin A1c (HbA1c) changesfrom baseline were -0.86 + 0.11,-0.46 + 0.12, and 0.12 + 0.09% in the10-mcg, 5-mcg, and placebo arms,respectively (P <.001). For participantswith baseline HbA1c >7%, the 10-mcgand 5-mcg Byetta arms reached anHbA1c &#8804;7%, significantly greater thanthe placebo arm (P <.0001). Furthermore,progressive dose-dependentweight loss was observed in the 10-mcg and 5-mcg Byetta arms, comparedwith baseline.5

Another 28-day, triple-blind, parallel-group, placebo-controlled studyexamined the efficacy and safety of 3different subcutaneous Byetta regimens.A total of 109 patients with type2 diabetes who had been stable on asulfonylurea and/or metformin regimenfor 6 months took part in thisstudy. Patients were enrolled to receiveByetta twice daily at breakfast and dinner,Byetta twice daily at breakfast andbedtime, Byetta 3 times daily (at breakfast,dinner, and bedtime), or placebo.At day 28, patients in the Byetta armshad a statistically significant reductionin serum fructosamine (P <.004) andHbA1c (P <.006), compared with thosein the placebo arm. Furthermore, end-of-study HbA1c of <7% was achieved by15% of all Byetta patients, comparedwith 4% of placebo-treated patients.Moreover, the beta-cell index for Byettapatients at day 14 and day 28ranged from 50% to 100% greater thanbaseline, while the beta-cell index forthe placebo group showed no change.6

Safety

The most common adverse eventreported with Byetta was dose-dependentmild-to-moderate nausea. Otheradverse events included vomiting,diarrhea, jitters, dizziness, headache,and dyspepsia.3,4 When Byetta is usedwith a sulfonylurea, mild-to-moderatehypoglycemia is observed; thus dosereduction is advisable. This effect hasnot been witnessed with metformin.4In addition, Byetta is not recommendedfor patients with severe renalimpairment, end-stage renal disease(creatinine clearance <30 mL/min), orsevere gastrointestinal disease.3

The delayed gastric emptying thatmay occur with Byetta may affect someconcentration-sensitive drugs—for example,antibiotics and/or oral contraceptives.Patients should be advised totake these medications at least 1 hourbefore a Byetta injection. Byetta is inPregnancy Risk Category C.

Outlook

The appealing side-effect and efficacyprofile of Byetta, along with theconvenience of prefilled pens, grantshealth care practitioners another therapeuticoption for the control of type2 diabetes, subsequent to unsuccessfultreatment with metformin or a sulfonylurea.

Drs. Faria and Soo are both senior researchpharmacists with the Investigational DrugService at Brigham and Women's Hospital,Boston, Mass. Dr. Faria also is a seniorhuman research specialist at PartnersHealthCare System. Diem Chi Tran is asixth-year PharmD candidate from theMassachusetts College of Pharmacycurrently on clinical clerkship in theInvestigational Drug Service at Brigham andWomen's Hospital.

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