Long-term weight control study III (weeks 104 to 156): An open-label study of dose adjustment of fenfluramine and phentermine

Between weeks 104 and 156 we attempted to optimize response by adjusting the doses of fenfluramine and phentermine. Dosing changes were based on an algorithm that aimed to achieve 120% of ideal body weight (IBW) while minimizing adverse effects. The dose groups were as follows: stage I, 30 mg fenfluramine plus 15 mg phentermine in the morning; stage II - continuous or targeted intermittent, 60 mg fenfluramine plus 15 mg phentermine in the morning; stage III, 60 mg fenfluramine plus 30 mg phentermine in the morning; stage IV, 60 mg fenfluramine plus 30 mg phentermine in the morning and 30 mg fenfluramine in the evening; and stage V, 60 mg fenfluramine plus 30 mg phentermine in the morning and 60 mg fenfluramine in the evening. Seventy-seven participants began this segment of the study and 59 completed to week 156. Completers of this segment of the study gained an average of 2.7 ± 0.5 kg between weeks 104 and 156 but remained 9.4 ± 0.8 kg (10.5%) below baseline. On average, weight loss from baseline by group was as follows: for stage I (n = 2), 14.1 ± 6.8 kg; for stage II continuous (n = 14), 10.9 ± 0.7 kg; for stage II targeted intermittent (n = 7), 8.8 ± 2.4 kg; for stage III (n = 9), 7.7 ± 2.6 kg; for stage IV (n = 8), 10.5 ± 2.6 kg; and for stage V (n = 19), 8.4 ± 2.4 kg. Upward dose adjustment (n = 36) resulted in further weight loss in 11 and no gain in six participants. Twelve participants were ≤120% of their IBWs and 24 additional participants were ≤130% of their IBWs at week 156. Visual analog scales indicated maintained medication effect and, even with increased doses, less medication bother. Of the 18 participants who dropped out of the study during this phase, three left because of adverse effects. At week 156, 14 participants had 21 complaints (dry mouth [7], central nervous system [6], gastrointestinal [6], and cardiovascular [2]). Overall, fenfluramine plus phentermine in conjunction with behavior modification, caloric restrictions, and exercise continued to help participants maintain weight loss for up to 3 years. Medication dose adjustment provided a modest additional benefit in some participants.