ORIGINAL ARTICLE Weight loss with sibutramine improves glycaemic control and other metabolic parameters in obese patients with type 2 diabetes mellitus K. Fujioka, 1 T.B. Seaton, 2 E. Rowe, 2 C.A. Jelinek, 2 P. Raskin, 3 H.E. Lebovitz, 4 S.P. Weinstein 2 and the Sibutramine/Diabetes Clinical Study Group* 1 Nutrition and Metabolic Research Center, Scripps Clinic, San Diego, CA, USA 2 Knoll Pharmaceutical Company, Mount Olive, NJ, USA 3 Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA 4 DepartmentofMedicine,DivisionofEndocrinologyandMetabolism,SUNYHealthScienceCenteratBrooklyn,Brooklyn,NY,USA Aim: Todeterminetheef®cacyandtolerabilityofsibutraminehydrochlorideinobesepatients whosetype2diabeteswaspoorlycontrolledondietaloneorwithanoralantidiabeticagent Methods: Thisstudywasa24-week,double-blind,multicentretrialfollowinga5-weekplacebo run-inperiod.Onehundredandseventy-®veobese(bodymassindex(b.m.i.) >27kg/m 2 )patients withpoorlycontrolledtype2diabetesmellituswererandomizedeithertosibutramine(n=89; meanage53.5years;meanweight99.3kg)orplacebo(n=86;meanage55years;meanweight 98.2kg)at16participatingcentres.Toachievemoderatecalorierestriction(de®cit > 250±500 kcal/day),individualdietarycounsellingwasaccompaniedbyeitherplaceboorsibutramine (initialdosageof5mg/daytitratedupby5mgbiweeklythroughweek6,andmaintainedat20mg throughweek24).Themainoutcomemeasuresincludedchangesinweight,b.m.i.,waistandhip circumference,glycaemiccontrol,lipidpro®le,andqualityoflife,andevaluationofreported adverseevents. Results: Sixty-sevenpercentofsibutraminepatientsand71%ofplacebopatientscompletedthe study.Atweek24whencomparingthosewhocompletedthecourse,sibutraminecomparedwith placebopatientsshowedsigni®cantlygreater(p<0.001)absolute(±4.3vs.±0.4kg)andpercentage (±4.5%vs.±0.5%)weightloss.Weightloss >5%or10%wasachievedby33%and8%of sibutraminepatients,respectively,butnoplacebopatients(p<0.03orbetter).Improvementin glycaemiccontrolwascorrelatedwithweightloss(p<0.001).In5%and10%weight-loss responders,meantreatmentdifferenceswere±0.53%and±1.65%(p < 0.05),respectively,for HbA 1c ,and±1.4mmol/l(p <0.05)and±3.8(p <0.05)mmol/lforfastingplasmaglucose. Sibutraminepatientsalsoshowedimprovementsinfastinginsulin,triglycerides,HDL cholesterol,andquality-of-lifeassessments.Overall,sibutraminewaswelltoleratedcompared withtheplacebo.Sibutraminetreatmentwasassociatedwithsmallmeanincreasesinblood pressure(BP)andpulse,althoughanincreaseinBPwasnotseeninsibutramine-treatedpatients wholost > 5%oftheirweight. Conclusions: Sibutramineproducedstatisticallyandclinicallysigni®cantweightlosswhen usedincombinationwithrecommendationsformoderatecaloricrestriction.Thisweightlosswas associatedwithimprovementsinmetaboliccontrolandqualityoflife,andsibutraminewas generallywelltoleratedinobesepatientswithtype2diabetes. Keywords: antiobesity agents, diet, serotonin, norepinephrine, sibutramine Received 1 November 1999; returned for revision 18 November 1999; revised version accepted 13 January 2000 Correspondence: K. Fujioka, Nutrition and Metabolic Research Center, Scripps Clinic, 12395 El Camino Real, Suite 315, San Diego, CA 92130, USA. E-mail: kfujioka@scrippsclinic.com *Listed in the Acknowledgements. | OA ã 2000 Blackwell Science Ltd Diabetes, Obesity and Metabolism, 2, 2000, 175±187 | 175