Rationale: Eight RCT articles considered the effects of pharmacotherapy on weight loss and subsequent changes in blood glucose (386, 387, 390-393, 408, 414).
Six trials in nondiabetic individuals reported weight loss with anorexiant drugs (386, 387, 390-393). One study of 75 subjects with refractory obesity showed that those taking dexfenfluramine had a significantly better improvement in their blood glucose levels as compared to placebo controls (390). Another trial showed that after 6 months on dexfenfluramine, fasting serum insulin levels fell from 105 at baseline to 89 at 6 months, but glucose levels did not decrease (392). This study was difficult to interpret. Four other RCTs of dexfenfluramine failed to show any significant differences between the active drug and placebo groups for glucose or insulin, despite significant differences in weight reduction (386, 387, 391, 393).
Among diabetic patients, there were two trials of anorexiant drugs. One trial of dexfenfluramine compared with standard clinic practice showed significantly greater weight loss at 3 months but not at 6 or 12 months (414). Weight loss at 3 months was 3.4 kg (7.5 lb) in the dexfenfluramine group and 1.59 kg (3.5 lb) in the clinic group. At 6 months, the weight loss was 3.13 kg (6.9 lb) in the dexfenfluramine group and 1.70 kg (3.7 lb) in the clinic group. By 1 year, both groups had regained some weight. Despite more than a 1 kg (2.2 lb) difference of weight between the dexfenfluramine group and the control group, there were no significant differences between groups in changes from baseline for HbA1c at any of the follow-up times (3, 6, or 12 months). In the trial of fluoxetine, those patients on 60 mg of fluoxetine daily compared with the placebo group had significant weight loss at 6 months, a finding that was associated with improvements in glucose and HbA1c . At 12 months, these differences were no longer significant (408). The RCTs of orlistat showed a drop in both fasting glucose and HbAlc in diabetic patients on a combination therapy of lifestyle change and orlistat for weight loss (388).