Effects of anti-obesity drugs, diet and exercise on weight-loss maintenance after a very-low-calorie diet or low-calorie-diet: a systematic review and meta-analysis of randomized controlled trails


Kari Johansson, Martin Neovius and Erik Hemmingsson


American Journal of Obesity. 2014 Jan;99(1):14-23


The purpose was to evaluate the effect of treatment with pharmaceuticals against obesity, diet and exercise upon weight checks, following initial weight loss with VLCD/LCD.


Maintenance of weight following weight loss is a great challenge in the treatment of obesity. Treatment with VLCD/LCD is associated with a substantial initial weight loss, but also with a larger weight rebound compared with weight loss involving a moderate reduction of energy intake. Maintaining a major weight loss requires substantial efforts, especially when non-surgical methods are used.

The effects of different strategies for weight control following a VLCD have previously been examined in several randomised studies. These have inter alia examined pharmaceuticals against obesity, meal replacements, high-protein food, food with a low glycaemic index, low-fat food, green tea extract, prolonged reintroduction period, the use of a corset and physical activity. The effect of the strategies for weight control have, on the other hand, been unclear, and the latest meta-analyses that have studied the long-term effect of VLCD has only made comparisons between VLCD and LCD treatments.


Material was gathered from randomised controlled studies from 1981 to February 2013 with initial treatment with VLCD/LCD (<1000 kcal/day) followed by randomised follow-up strategies to maintain the weight, alternatively the control group.


20 studies were included with a total of 3017 participants, all of whom were over 18 years of age, between 24 and 48 years of age and having a BMI of 27.9 to 41.6. The time period for weight monitoring lasted between three months and three years, of which 1220 studies had a period of more than one year. The studies were divided into 27 groups with the following treatment categories: 3 studies with pharmaceuticals against obesity, 4 studies with meal replacements, 3 studies with high-protein food, 6 studies with nutritional supplements, 2 studies with other food and 5 studies with exercise.

During the VLCD/LCD period, weight loss was an average of -12.3 kg (treatment time 8 weeks, with a variation at 3 to 16 weeks). Compared with the control group, the difference in weight recoil in the case of pharmaceuticals to control obesity were on average 3.5 kg over the course of 18 months (12-36 months), meal replacements 3.9 kg over 12 months (10-26 months) and high-protein diet 1.5 kg over 5 months (3-12 months).

The effect of exercise and dietary supplements showed no significant difference compared with the control group.


Pharmaceutical treatment to control obesity showed positive results; however, it is also shown to be associated with risks for side effects, which meant that the most effective preparations were withdrawn.

Meal replacements are both high in nutrients and low in energy and can serve both directly and indirectly to reduce energy intake. Many patients with obesity underestimate their energy intake, and meal replacements can be effective in reducing patients’ choice of foodstuffs and can thus facilitate a balanced energy intake.

High protein food with 20-30 E% has been shown to provide an increased sense of satisfaction, maintain a larger share of fat-free mass and maintain energy consumption in diet-induced thermogenesis.

Even if it were not found that exercise demonstrated improved weight control, other studies have shown that exercise is effective for long-term weight control, even after a period of weight loss. 2 of 3 studies showed that exercise is effective for weight control in the short term, while the effect in the long term was negative, probably due to the adherence to the amount of exercise needed for weight control (60-90 min/day).


Pharmaceuticals to control obesity, meal replacements and high protein food are associated with improved weight control after weight loss during a VLCD/LCD period, while no significant difference was found for nutritional supplements and exercise. In the meta-analysis, pharmaceuticals to control obesity and meal replacements showed the greatest effect on weight control after a VLCD/LCD diet.