Here, we show in a large cohort of patients with grade I–III obesity that a non-surgical obesity therapy program performed in specialized centers under ambulatory conditions over 52 weeks is highly effective in reducing body weight and obesity-associated diseases after 12 month. According to the WHO definition of successful weight loss (>10% loss of initial body weight), the grand majority of participants (81% according to PP and 64% according to ITT analysis) were successful after 1 year of treatment. Of the successful people, 2/3 achieved a weight loss of >15%, independent of the type of statistical analysis, a result not documented before by other non-surgical intervention programs. Moreover, WC was substantially reduced (by 21
cm in males and 16
cm in females), which could be of major clinical relevance, because already a 3
cm reduction of WC results in significant improvement of cardiometabolic risk factors.19
Interestingly, the effects were more pronounced in male than in female participants. This gender difference is most likely due to the fact that (1) males entered the program with higher body weights and higher BMI and (2) an energy intake of 800
kcal per day means a more pronounced restriction for males than for females.10
The beneficial effects of the program on body weight were not restricted to particular ranges of initial body weight. Weight reduction was most pronounced in participants with an initial BMI of >40–50
, but the effects were almost as good in patients with moderate obesity (BMI 30–40
) and in patients with severe obesity (BMI >50
) who are often referred for bariatric surgery. Not only anthropometric, but also other risk parameters defining the MS were strongly reduced. Of particular importance is the pronounced effect of the intervention on blood pressure, which confirms previous reports.20, 21
Among patients with hypertension at program entry, blood pressure was reduced to an extent similar to that achieved by pharmacological treatment.21
These data strongly suggest that a non-surgical obesity therapy program performed under medical supervision not only reduces risk of metabolic diseases, but also has substantial drug cost-saving effects.
An important strength of the study is the fact that we included all participants who started the program without selection during a 8.5-year-period of evaluation, which moderates the drawback because of lack of a randomized controlled study design for obvious technical and ethical reasons. Results might be biased if only patients from centers with above average therapeutic care are included in evaluations. This has also to be taken into account when comparing the results with bariatric surgery, as only a fraction of all operated patients are evaluated in studies. The relevance of our data is further strengthened by three additional findings: (1) a clear association between improvement of markers of physical health and HRQOL, (2) signs of a sustained benefit beyond the intervention period of 1 year and (3) no relevant adverse effects after a careful analysis of safety over 10 years of experience.
Most importantly, our data also show that the weight loss achieved after 6 months of treatment were stabilized in most cases until the end of the program. Minor weight gain within week 27–52 of treatment was approximately 3
kg. Rapid weight gain within weeks (‘yo-yo-effect') was not observed. The question often asked is whether a non-invasive treatment can maintain its effect beyond the 1-year-treatment period. In the past, the expectations were high in this respect, although no defined intervention followed the 1-year-program. Interestingly, we found in a subgroup of 301 participants from whom long-term data were available for analysis, that weight loss based on the initial body weight is still statistically highly significant and clinically substantial after 3 years of observation.
Concerning safety, a non-surgical intervention is generally preferable to an invasive therapy, because it does not alter the integrity of the digestive tract and has no irreversible consequences. Indeed, the few adverse events we saw were thoroughly harmless and infrequent, except the risk of biliary disease among people who lose weight through LCD, because of the missing stimulus for gallbladder contraction. However, not only restriction diets, but also obesity per se
may account for the enhanced risk of cholelithiasis and sludge,22, 23
promoted by an increased hepatic secretion of cholesterol.24
The risk rises linearly with increasing obesity25
and is particularly high in women with extreme obesity.26
Two cases of death (0.02%) and five cases of malignant diseases (0.05%) occured within the year of intervention among 8296 participants. Taken into consideration that obesity was found to be associated with enhanced cancer incidence27
the two reported cases of death do not at all suggest an increased mortality related to the intervention program.
Our data revealed that OF52 is for now almost similarly effective as several invasive treatment options for obesity such as banding or vertical gastroplasty, as reported in the Swedish Obese Subjects study in which individuals with similar initial BMI were included.29, 30
In completers, the average excess weight loss after our non-surgical intervention was 53%, which is close to the overall weight loss of 61% reported in a meta-analysis about bariatric surgery.31
Only the more invasive gastric bypass seems to be clearly more effective than the non-surgical obesity therapy program tested here.
Most recently, the randomized controlled Louisiana Obese Subjects Study32
showed that a 24-month-non-surgical primary care practice program with LCD (890
kcal per day) for up to 12 weeks, meal replacements and choice of pharmacotherapy is highly effective in a primary care setting. However, although participants in our study were less obese than in LOSS, RWL at 1 year was higher after OF52 (17.9%), compared with LOSS (13.1%). The higher effectiveness we achieved could be because our program is more precisely structured and contains more intensive external therapeutic support, combined with regular exercise program and a complete full meal replacement for 12 weeks for all participants. Another primary care approach with similar results as reported in the LOSS study has been published from the UK some years earlier.33
Such data indicate that structured interdisciplinary programs performed in specialized centers might be more effective than primary care approaches.
Our data indicate that the OF52 program is more effective than primary care practice program within an observation time of 12 month. Compared with other medically supervised proprietary programs, the OF52 outcome data are comparable to what has been reported for other programs when looking at the 3–6 month data (RWL 20% here versus 15–25% in Tsai and Wadden8
). However, OF52 is definitively more effective after 12 month (18% here versus 8–9% in Tsai and Wadden8
). Interestingly, the advantage of OF52 seen after 12 month seem to disappear after 3 years (4.2% here versus 7% in Tsai and Wadden8
), suggesting that without continuation of treatment, the effects will fade away with time. At present, it is unclear if this long-term weakness of non-surgical programs, and to some extent also of surgical interventions, is unavoidable or just a result of the lack of appropriate follow-up programs after the initially successful intervention.
The advantages of conservative programs (higher acceptance rate, low rates of adverse events and lower costs) are contrasted by reports suggesting higher relapse rates, compared with those after bariatric surgery. However, our data confirm previous reports showing that non-surgical interventions, even though they differed to the program we accomplished here, are still effective up to 5 years after start.9
Most importantly, the rate of weight loss achieved by using the LCD within the first weeks of the program seems to be not only highly motivating, but also the most effective non-surgical method of sustained weight loss.11
According to our preliminary long-term data, about 30% of the patients were successful regarding weight reduction over a time period of 3 years. Of them, 7% successfully maintain or even further reduce their weight after intervention without further support and 22% of the participants slowly regain weight, but still remain clearly below their initial weight. Self-reported physical activity, treatment adherence and consumption of meal replacements were identified as most relevant factors associated with success.34
Interestingly, even after surgical intervention, a certain weight gain is observed.29, 30
The relative weight gain 3 years after lowest recorded weight is about 5% in surgery studies and 15% in our study, indicating the necessity of effective weight maintenance programs that must follow all primary interventions, even those with 12 months initial duration. On the other hand, bariatric surgery, depending on the extent of malabsorption induced, is definitely less prone to the risk of weight regain compared with all non-surgical intervention programs. To which extent this major problem of even initially successful non-surgical programs like OF52 can be attenuated by appropriate follow-up interventions needs to be studied in future trials.
In conclusion, we demonstrated that defined non-surgical intervention programs such as the OF52 program could be highly effective in reducing body weight and risks of obesity-associated diseases. Therefore, we propose such an approach as promising choice for the primary treatment of obesity in adults and confirm it to be the first option before considering bariatric surgery.