OBJECTIVES: The 1998 NHLBI Obesity Guidelines state "extremely obese persons often do not benefit from more conservative treatments for WL.” This post-hoc analysis explores the use of PHEN/TPM ER, a pharmacologic adjunct to lifestyle modifications, to impact WL across BMI ranges, including extreme obesity. METHODS: Data from two double-blind, placebo-controlled Phase 3 studies (CONQUER [BMI ≥27 to ≤45kg/m2], EQUIP [BMI ≥35kg/m2]) were pooled and subjects stratified by baseline BMI (kg/m2; <30, ≥30-<35, ≥35-<40, ≥40-<45, ≥45) and by randomized dose over 56 weeks (ITT-LOCF). Subjects were randomized to placebo (n=1477), PHEN 3.75mg/TPM ER 23mg (3.75/23; n=234), PHEN 7.5mg/TPM ER 46mg (7.5/46; n=488), or PHEN 15mg/TPM ER 92mg (15/92; n=1479). All subjects received the same lifestyle intervention. RESULTS: At baseline, mean weight was 107.4 kg and mean BMI was 38.4 kg/m2. At week 56, least-squares mean percent WL was -1.5%, -4.7%, -8.2%, and -10.4% for placebo, 3.75/23, 7.5/46, and 15/92, respectively (P<.0001 versus placebo). Similar dose trends were seen when subjects were stratified by baseline BMI for placebo, 3.75/23, 7.5/46, and 15/92, respectively: BMI <30, -1.1%, dose not included in CONQUER, -9.1%, and -9.1%; BMI ≥30-<35, -1.8%, -10.3%, -8.0%, and -10.4%; BMI ≥35-<40, -1.8%, -5.5%, -8.8%, and -10.2%; BMI ≥40-<45, -1.9%, -4.4%, -8.3%, and -11.5%; and BMI ≥45, -1.3%, -5.5%, -8.8%, and -11.0% (P<0.005 versus placebo, all comparisons with 7.5/46 and 15/92). Similar WL trends were observed with mean absolute WL (P<0.005 versus placebo, all comparisons with 7.5/46 and 15/92). Common adverse events were constipation, dry mouth, and paraesthesia. CONCLUSIONS: PHEN/TPM ER was associated with significant WL versus placebo across all BMI categories, with dose proportional percent WL increases across BMI categories within each treatment arm. We conclude that significant WL is possible across a wide range of BMIs, including extreme obesity, with PHEN/TPM ER use.