Rx PRODUCT NEWS PROFILE: Byetta (exenatide)

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 A_1c (HbA_1c) 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 HbA_1c >7%, the 10-mcgand 5-mcg Byetta arms reached anHbA_1c &#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) andHbA_1c (P <.006), compared with thosein the placebo arm. Furthermore, end-of-study HbA_1c 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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