Initial weight loss as a predictor of response to obesity drugs.

BACKGROUND: Initial weight loss has been used as a predictor of long-term response to obesity drugs. Discontinuation of drugs has been recommended if weight loss is not > or =1.81 kg (4 lb) in the first month of treatment. OBJECTIVE: We compared the weight loss response at 6 months of patients losing > or =1.81 kg (responders) vs. < 1.81 kg (non-responders) in the first month of treatment with the combination of fenfluramine and phentermine. DESIGN: Outcomes at 6 months in 975 patients treated in a comprehensive program of phentermine (15-30 mg/d) d,l-fenfluramine (20-60 mg/d), were compared for responders vs. non-responders. RESULTS: In the total population, first month weight loss highly correlated with % reduction in body mass index (BMI) after 6 months of treatment (P<0.001). The reduction in baseline BMI after 6 months treatment was greater for the responders (15.9% vs. 10%, P<0.02). However, the North American Association for the Study of Obesity (NAASO) guidelines for drug treatment of obesity state that a 5% weight loss produces significant health benefits, and may be used as a criteria for success. At 6 months, 76%, 37% and 14% of the non-respondents had lost > or = 5%, > or = 10% and > or = 15% of baseline BMI, respectively. After 6 months treatment the reductions in serum cholesterol, triglycerides and LDL-cholesterol were 0.55, 0.31 and 0.42 mmol/L, respectively, (P< or =0.006), for the non-responders. Adverse effects after 6 months of treatment and the dropout rates after 1 y of treatment were not significantly different for the two groups. CONCLUSIONS: Although, the first month weight loss predicted the long-term response to phen-fen treatment, it was inadequate in identifying the non-responders and may unnecessarily preclude potential beneficiaries of the treatment.

Long-term pharmacologic treatment of morbid obesity in a community practice.

OBJECTIVE: To determine the safety, efficacy, and metabolic changes in patients with morbid obesity treated with d,l-fenfluramine and phentermine in an open-label trial. METHODS: In patients with a body mass index (BMI) =40.0 kg/m 2 (N = 298) who sought assistance at a private medical practice for treatment of obesity, 60 mg of d,l-fenfluramine and 15 to 30 mg of phentermine resin were administered daily in an open-label trial, without placebo controls, for up to 24 months. The setting was a community-based private practice. Study subjects were given instructions for a 1,200 to 1,400 kcal/day diet, exercise, and behavior modification. Follow-up included a monthly medical visit, behavior modification group attendance, quarterly laboratory evaluation, and electrocardiographic monitoring. RESULTS: BMI decreased from 45.8 kg/m2 to 37.4 kg/m2 (P<0.0001) in those who completed 12 months of treatment and to 38.2 kg/m2 (P<0.0001) in those who continued the protocol for 24 months. Statistically significant decreases in fasting blood glucose, total and high-density lipoprotein cholesterol, triglycerides, systolic and diastolic blood pressures, and fasting insulin concentrations were noted. The dropout rate was 42.3% at 12 months and 69.8% at 24 months. The most common reason given for discontinuing participation in the study was "success" with the program (mean BMI loss of 7.8 kg/m2). Five patients discontinued treatment because of side effects. No laboratory or electrocardiographic abnormalities were noted that could be attributed to the medications. No statistically significant regain of weight occurred in those who completed 12 or 24 months of treatment. CONCLUSION: In this study, treatment of morbid obesity with d,l-fenfluramine and phentermine was safe and efficacious in promoting and maintaining weight loss. Moreover, statistically significant changes were noted in metabolic variables associated with risk of heart disease. Future efforts must focus on methods to improve long-term compliance.

Long-term drug treatment of obesity in a private practice setting.

This study evaluated the long-term efficacy and safety of the combination of phentermine and fenfluramine for the treatment of obesity in a private practice setting. A total of 1388 consecutive, qualified patients presenting to a private general internal medicine practice in Charlotte, NC, were enrolled with eligibility criteria including: age 18 years to 60 years, 20% over "desirable" bodyweight or body mass index > 27, no serious medical or psychiatric disease, and no contraindications to drug therapy. Patients were instructed in diet, exercise, and behavior modification techniques and received phentermine (15 mg/day to 30 mg/day) and fenfluramine (20 mg/day to 60 mg/day) continuously for over 3 years. Average duration of treatment was 15.9 months, and average weight loss at the last visit was 11.6 kg, or 11.7% of initial bodyweight. For patients completing 1 year of drug treatment, mean weight loss was 16.5 kg, or 16% of initial weight. Weight loss persisted for 2 years, but partial regain was seen at 3 years. The dropout rates were 18% at 6 months, 39% at 1 year, 68% at 2 years, and 78% at 3 years. At 1 year, blood pressure of hypertensive patients fell from 151/95 mm Hg to 127/78 mm Hg, and serum cholesterol and triglycerides of hyperlipidemic patient fell by 0.750 mmol/L (29 mg/dL) and 0.937 mmol/L (83 mg/dL), respectively. Adverse events were modest. We conclude that, in a private practice setting, long-term treatment of obesity with the combination of phentermine, fenfluramine, and a weight maintenance program is generally safe and effective. More research is needed to determine efficacy and safety for longer than 3 years.

Combined drug treatment of obesity.

Pharmacological treatment of obesity has been neglected as a viable therapeutic option for many years. Recent long term studies with combinations of obesity drugs gives promise that drugs may play a role in weight maintenance, which classically has been the most difficult aspect of treating obesity. Currently available obesity drugs include centrally acting adrenergic agents and serotonin agonists. Drugs still in development include a lipase inhibitor that produces fat malabsorption, a combined adrenergic-serotonergic reuptake inhibitor, various gut-central nervous system peptides, and a number of beta-3 agonists. Any of these obesity drugs given alone produces modest weight loss, and for most, weight loss continues for as long as medication is given. The most successful drug regimens to date are combinations of phentermine and fenfluramine or of ephedrine, caffeine, and/or aspirin. The former combination produces reduction in body weight and complications of obesity for 2 to almost 4 years in clinical trials to date. More research is needed to document long term efficacy and particularly the long term safety of these and other combinations.