Two-Year Outcome of a Combination of Weight Loss Therapies for Type 2 Diabetes

Objective: To evaluate the effects over 2 years of a weight loss program combining several weight loss strategies on weight loss and diabetes control in overweight subjects with type 2 diabetes.Research Design and Methods: A total of 59 overweight or obese individuals with type 2 diabetes were randomly assigned to either a combination therapy weight loss program for 2 years (C therapy) or a standard therapy weight loss program for 1 year followed by a combination therapy weight loss program in the 2nd year (S/C therapy). C therapy combined the use of meal replacement products, repetitive intermittent low-calorie-diet weeks, and pharmacologic therapy with sibutramine. Outcome measures included changes in weight, glycemic control, plasma lipids, blood pressure, and body composition over 2 years.Results: A total of 48 participants (23 in the C therapy group and 25 in the S/C therapy group) completed 2 years of study. After 2 years, the C therapy group had weight loss of 4.6 ± 1.2 kg ( P < 0.001) and a decrease in HbA1c of 0.5 ± 0.3% ( P = 0.08) from baseline. At 2 years, the C therapy group had significant reductions in BMI, fat mass, lean body mass, and systolic blood pressure. The S/C therapy group showed changes in weight and HbA1c in year 2 of the study that were similar to those demonstrated by the C therapy group in year 1.Conclusions: This combination weight loss program resulted in significant weight loss and improved diabetes control over a 2-year period in overweight subjects with type 2 diabetes.
Introduction
Weight loss is an important therapeutic objective for individuals with type 2 diabetes.[1] Short-term studies have demonstrated that weight loss in overweight or obese type 2 diabetic subjects is associated with decreased insulin resistance, improved measures of glycemic control, reduced lipemia, and reduced blood pressure.[2-4] However, the most recent American Diabetes Association nutrition recommendations concluded that "optimal strategies for preventing and treating obesity long term have yet to be defined".[5]
Long-term options to promote weight loss in people with type 2 diabetes include standard weight-reduction diets and very-low-calorie diets. However, standard weight-reduction diets are usually not effective.[5] Very-low-calorie diets produce substantial initial weight loss but do not maintain weight loss long term.[6]
Other approaches to weight loss that might be effective in type 2 diabetic subjects include use of meal replacements, repetitive use of low-calorie diets, and weight loss medications. Hensrud[7] reported significant weight loss at 3 months using meal replacements in type 2 diabetic subjects, but weight and measures of glycemic control trended toward baseline values at 1 year. Williams et al.[8] compared a standard diet to very-low-calorie diets used either 1 day per week or 5 consecutive days every 5 weeks in type 2 diabetic subjects. After 15 weeks, the very-low-calorie diet groups lost 9.6 and 10.4 kg, respectively, compared with weight loss of 5.4 kg in the standard diet group, but longer-term follow-up was not provided. Sibutramine treatment of type 2 diabetic subjects for 6 months produced weight loss of ~4.5% but had only modest effects on HbA1c in two studies[9,10] and, at a dose of 15 mg daily, produced weight loss of 5.5 kg and a decrement in HbA1c of 0.6% at 1 year in another study.[11] Three 1-year trials compared orlistat to placebo in type 2 diabetic subjects.[12-14] Weight loss at 1 year ranged from 4 to 6%, and decrements in HbA1c ranged from 0.5 to 0.9%.
With these studies in mind, we hypothesized that efficacy might be increased if several weight loss approaches were combined. Accordingly, we initiated a clinical trial combining intermittent low-calorie diets, energy-controlled meal replacements, and sibutramine to treat overweight and obese type 2 diabetic subjects. The 1-year results have previously been reported.[15] Herein, we report the 2-year results with primary focus on those subjects who received the combination therapy weight loss program throughout the entire 2 years of study.