1. Regardless of the initial rate of weight-loss (gradual or rapid), participants regained a similar proportion of weight after long-term follow-up.
2. Attrition rate was higher among participants assigned to the gradual weight-loss program when compared to those in the rapid weight-loss program.
3. Leptin levels decreased in both groups but fell more sharply in the rapid weight-loss group. Ghrelin levels increased in both groups after weight loss and remained high during weight maintenance.
Evidence Rating Level: 1 (Excellent)
Study Rundown: When counseling obese patients on weight-loss, a popular opinion is that patients who lose weight more rapidly tend to regain that weight more rapidly as well. The reasoning for this belief may be rooted in the perception that obesity is a behavioral problem and that gradual weight loss allows more time for habits to change. The investigators set out to examine whether the rate of weight loss affects weight regain and also aimed to analyze the ways in which rate of weight loss interacts with appetite-mediating hormonal levels. This trial was a randomized, two-phase dietary intervention. In phase 1, participants were assigned to either a rapid (12 week) or a gradual (36 week) weight loss program. Participants who were successful in phase 1 progressed to phase 2, a 144-week maintenance diet. The primary outcome was mean weight loss maintained at the end of phase 2. Other measures that were followed closely included fasting ghrelin and leptin concentrations.
During phase1, investigators found a significantly higher attrition rate in the rapid weight-loss program. 81% in the rapid weight-loss program lost 12.5% or more weight, compared to 62% in the gradual weight-loss group during phase 1. In those who progressed to phase 2, the average weight regained was not significantly different. With regard to hormonal levels, leptin trended downward during phase 1 in both groups and upward during phase 2, and ghrelin levels increased in both groups during phase 1 and remained high during phase 2. The findings suggest that the rate of initial weight loss does not have a significant impact on long-term weight maintenance in obese patients.
In-Depth [randomized controlled trial]: Patients aged 18-70 years were eligible if they were obese (BMI 30-45) and otherwise healthy. In phase 1 of the study, 200 participants were randomly assigned 1:1 to either a rapid (n=97) or gradual (n=103) weight loss program, which both aimed for 15% weight loss. The rapid weight loss program consisted of a very low energy diet (450-800 kcal per day) for 12 weeks. The gradual weight loss program consisted of an energy reduced diet (400-500 kcal per day deficit) for 36 weeks. Participants who lost 12.5% or more weight during phase 1 continued on to phase 2 to follow an individualized diet for weight maintenance, with follow-up at weeks 4 and 12, then every 12 weeks until 144 weeks. The primary endpoint was mean weight loss maintained after 144 weeks of phase 2.
179 participants (89.5%) completed phase 1. The attrition rate during phase 1 was significantly higher in the rapid vs. gradual weight-loss group (18% vs. 3%, p = 0.002). 76 of 94 (81%) in the rapid weight loss group who completed phase 1 had at least 12.5% weight-loss, compared to 53 of 85 (62%) in the gradual weight-loss group (p=0.009). During phase 2, both groups regained similar amounts of weight. The gradual weight-loss group regained 10.4kg on average (95% Confidence Interval [CI] 8.4-12.4; 71.2% regained weight, 95% CI 58.1-84.3), vs. 10.3kg (8.5-12.1; 70.5%, 57.8-83.2) in the rapid weight-loss group. Leptin dropped in both groups during phase 1, with a more pronounced decrease in the rapid weight-loss group (p= 0.03). Leptin increased in both groups during phase 2, with no significant difference between groups at 48 or 144 weeks. Ghrelin levels were not significantly different between the two groups but levels were increased after weight loss and remained high during phase 2. Additionally, one participant in the rapid weight-loss group developed cholecystitis during phase 1 and two participants in the rapid weight-loss group developed cancer during phase 2, which the authors attributed as unrelated to the dietary intervention.
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