2-Year Clinical Treatment For Obesity

July 02, 2021

Clinical Treatment of Obesity 


We understood that it is not the fact that patients with obesity are weaker to resist to food than lean people. Instead, Patients with obesity need to be much stronger to resist, since they are mostly genetically programmed not to resist to foods high in calories.

We also understand that the use of safe medications for weight loss will more likely bring benefits than harms, in particular the multiple harms caused by obesity.

In this approach, we combined different on- and off-label drugs with a comprehensive approach of psychotherapy, personalized diet, and/or personal trainer, with a strict surveillance. Unlike what is typically seen, drugs were not interrupted suddenly when final weight loss was achieved. Instead, we kept medications for longer and reduced them slowly, just like it is done with any chronic treatment. Instead of calling as maintenance the period after weight loss goal is achieved, we termed as consolidation, since we consider this immediately post-weight loss period quite unstable.

These bases allowed us to have a 93% of successful rate to avoid bariatric surgery in more than 40 patients, with less than 20% that regained more than 10% of the weight loss in the two following years.

Clinical weight loss is feasible if we understand the complex pathophysiology of obesity, the multiple pitfalls patients face during their weight loss processes, removing the guilt from the patients since this is majorly a result from strong genetic predisposition, and that like any other chronic disease, relapses are expected and pharmacotherapy should not be considered if used only in the short run. The stigma of the pharmacotherapy for obesity caused by the historical misuse of anti-obesity drugs should be fought. 




Cadegiani FA et al. Aggressive clinical approach to obesity improves metabolic and clinical outcomes and can prevent bariatric surgery: a single center experience. BMC Obes. 2017 Feb 21;4:9. DOI: 

Study Abstract 

Background: The number of bariatric procedures has exponentially increased in the past decade, as a result of the lack of successful clinical weight-loss interventions. The main reasons for the failure of clinical obesity management are: (1) anti-obesity medications are administered as monotherapies (or pre-combined drugs); (2) lack of combination between pharmacotherapy and non-pharmacological modalities; (3) short duration of pharmacotherapy for obesity; (4) lack of weight-loss maintenance strategies; (5) misunderstanding of the complex pathophysiology of obesity; and (6) underprescription of anti-obesity medications. We developed a protocol that can potentially overcome the drawbacks that may lead to the failure of clinical therapy for obesity. The aim of this study is therefore to report the clinical and metabolic effects of our proposed obesity-management protocol over a 2-year period, and to determine whether this more intensive approach to obesity management is feasible and a possible alternative to bariatric surgery in patients with moderate-to-severe obesity.

Methods: This retrospective study involved 43 patients in whom bariatric surgery was indicated. Patients underwent an intensive anti-obesity protocol that included pharmacotherapy with multiple drugs; intense surveillance with monthly body analysis by air-displacement plethysmography, electrical bioimpedance, and 3D body scans; weekly psychotherapy; diet planning with a dietician every 2 months; and exercises at least 3 times a week with exercises prescribed by a personal trainer at least once a month. Body weight (BW), total weight excess (TWE), obesity class, body mass index, fat weight, muscle weight, waist circumference, and visceral fat were analyzed. Markers of lipid and glucose metabolism, liver function, and inflammation were also evaluated. Therapeutic success was defined as >20% BW loss or >50% decrease in TWE after 1 year.

Results: Significant improvements were observed in all clinical and metabolic parameters. Thirty-eight (88.4%) patients achieved 10% BW loss, and 32 (74.4%) achieved 20% BW loss. TWE decreased by >50% in 35 (81.4%) patients. Forty (93.0%) patients were able to avoid bariatric surgery.

Conclusion: An intensive clinical approach to obesity management can be an effective alternative to bariatric surgery, although further randomized controlled studies are necessary to validate our findings.








A Solution For Dumping Syndrome?

July 02, 2021

Post-bariatric care: A solution for Dumping Syndrome? 


After bariatric surgery, many patients experiment a huge discomfort when eating higher loads of white or simple carbohydrates, presenting adrenergic, hypoglycemic, and gastrointestinal symptoms, and has a specific name: Dumping syndrome. Patients that present this event frequently tend to naturally avoid high-carbohydrate or sugar sources of food, as a sort of educational process, although not necessarily the most adequate manner to change eating habits.

Dumping syndrome can be divided into early and late dumping. Early dumping happens due to a sort of an active secretion from the gastrointestinal tract lumen leading to an “acute water loss”, causing autonomic symptoms. Late dumping occurs due to the excessively exposure of glucose to the small bowel, leading to massive glucose absorption and amounts of incretin hormones released, that overstimulates insulin secretion, leading to a reactive hypoglycemia.

We would consider that the use of an alpha glucosidase inhibitor, that delays the sugar and carbohydrate digestion, would only work for late dumping.

However, when we tested in patients, improvements of dumping syndrome occurred in both early and late dumping. The reasons why it helped improved early dumping are yet to be clarified. 



Cadegiani FA et al. Acarbose promotes remission of both early and late dumping syndromes in post-bariatric patients. Diabetes Metab Syndr Obes. 2016 Dec 7;9:443-446. DOI: 10.2147/DMSO.S123244. 

Study Abstract

Objective: Acarbose is a glucosidase inhibitor that slows carbohydrate digestion. It could thus be effective to promote remission of dumping syndrome (DS). Previous studies associating acarbose and late dumping, although not early dumping, have been reported. Herein, we aimed to evaluate the role of acarbose in dumping syndrome prevention and treatment and in resistive exercises resistance in bariatric subjects.

Methods: Bariatric patients with DS and complete adherence to diet plan and resistive exercises were included (n=25). Number of early and late episodes, self-referred intensity of each episode, and ability to increase intensity of resistive exercise were evaluated, on a 0-10 scale. Acarbose was administered orally (50 mg) for 6 months, 4-5 times a day before meals.

Results: Acarbose administration was associated with a decrease in the number of early (2.18-0.31) and late (2.79-0.12) episodes per week and intensity of each episode (6.10-1.65) and an increase in the ability to perform resistive exercises (3.03-7.12). Complete remission of DS was seen in 21 patients (84%), which persisted for 6 months with the use of acarbose.

Conclusion: Acarbose prevented dumping in almost all studied subjects and helped improve exercise capacity.



Paradoxical Markers Of Weight-Loss

July 02, 2021

What happens in weight loss? 


Our protocol for weight loss of patients with moderate or severe obesity includes a thorough analysis of the blood parameters on a regular basis.

We started to notice that some markers of “cardiovascular risk” paradoxically increased during weight loss, specially when fat loss was a large component.

In this study, we demonstrated that fat loss was linearly and inversely correlated with homocysteine and triglycerides, while directly correlated with folic acid, apoA, and HDLc. However, these changes were transitory, and normalized after stabilization of body weight.

Other markers were found, obviously, because we followed 65 parameters, including linear and significant reductions of GGT, ALT, usCRP, ESR, neutrophils, ferritin, fibrinogen, PTH, apoB (that reduced disproportionally more than LDLc), LDLc 



Cadegiani F, da Silva PLH. Novel Paradoxical Markers of Weight Loss: Is the Worse Actually the Better? a Retrospectiv eanalysis of 1,567 Patients with Obesity With Successful Clinical Weight-Loss Approaches. J Endocr Soc. 2020;4(Suppl 1):MON-LB100. Published 2020 May 8. doi:10.1210/jendso/bvaa046.2338. 

Study Abstract

Background: Obesity is a chronic, multi-factorial, and relapsing disorder that has been reported to be a risk factor to more than 200 diseases, among which the majority is direct- or indirectly triggered by the metabolic abnormalities induced by excessive body fat. Indeed, patients with obesity tend to disclose multiple alterations of metabolic markers, which tend to improve with weight loss. Despite the multiple dysfunctions extensively in this population, only mandatory biochemical exams are usually ordered, likely due to limitations in cost and lack of cost-effectiveness, since the majority of the parameters typically altered in obesity does not drive therapeutic choices or influence in an individual-based evaluation.We developed a protocol for obesity treatment that includes a thorough analysis and follow up of the biochemical parameters of patients with obesity, including more than 50 parameters, for more precise diagnosis and response to treatments. Among these parameters, we identified unexpected changes, including some that would initially be related to increased cardiovascular risk or worse prognosis when in an usual context, but which could peculiarly indicate successfulness of weight loss, since these parameters tend to return to normal levels after a period in the new body weight. Our objective is to identify whether these paradoxical changes in biomarkers are linearly correlated with body weight loss, fat loss, mass loss, or whether they were related to the use of any anti-obesity drug. 

Methods: In a retrospective cohort of 1,567 patients that underwent a clinical weight loss treatment for obesity in a obesity center (Corpometria Institute, Brasília, DF, Brazil), we performed a linear association analysis between body weight and body fat (air displacement pletismography - Bod Pod, CosMed, USA) and 65 parameters, including hormonal, metabolic, inflammatory, and immunologic parameters. We also adjusted for the use of anti-obesity drugs. 

Results: Homocysteine and triglycerides were identified to increase linearly according to the amount of weight loss (r = -0.77) and fat loss (r = -0.85), but not due to the use of any drug. Folic acid decrease was directly related to fat loss (r = 0.81). Additional findings include more significant decrease of ApoB, compared to LDLc, decreases of GGT, ALT, CRP, ESR, neutrophils, ferritin, fibrinogen, PTH, free T3, uric acid, a and temporary decrease of ApoA and HDLc, all related with body fat loss. 

Conclusions: Increase of homocysteine resulted from decreased folic acid metabolism, and increased triglycerides may be indirect markers of lipolysis, as no other plausible mechanism could explain these findings.




Weight Regain

July 02, 2021

The weight yo-yo drama 


One of the main reasons why patients with obesity give up trying to lose weight is the almost unavoidable weight regain that occurs in more than 95% of the times after a weight loss therapy.

However, there are important addressable reasons why weight regain occurs. First, weight loss is not a natural process, and those with obesity corresponds exactly to those whose bodies will complain when their ‘storage’ is decreasing. Hunger and craving increase, metabolic rate decreases, efficiency of energy storage increases, anorexigen hormones decrease abruptly while orexigens increase, and everything else that someone who is losing weight can experiment. This are biological strategies to prevent further loss of storage and an attempt to re-store all the energy again, since patients with obesity more likely kept the genes that saved the human bean from long periods of starvation and shortage of food, in particular the FTO gene.

Once we know all these pitfalls during the weight loss process, that become even harder to handle after the weight loss is finished, we can perfectly try to address these issues. However, the understanding that obesity is a chronic and inherently relapsing condition is mandatory for an appropriate long-term approach to obesity.

In the present analysis, we show the results of a 5-year follow up of patients with previous severe obesity, that had a 93% successful rate in weight loss and a 2-year follow-up, as published in 2017 in the BMC Obesity journal.

For the 5-year, the 40 patients the 43 that were successful in the 2-year follow-up were included. These patients were continuously but less frequently followed, kept at least one intervention between diet, physical activity, and/or psychotherapy, and followed one of the three possibilities in terms of drug therapy: 1. Kept one or part of the drugs in the long-run (which is better and less risky than regaining weight); 2. Used drugs in an intermittent manner (for example, 06 months per year); or 3. Were kept off medications. Patients could change between these 03 options during the follow-up.

Of the 40 patients, 27 were able to maintain the weight loss for 05 years, 07 abandoned the follow-up, and 06 regained more than 20% of the weight previously lost. The improvements observed in the biochemical profile maintained along the 05 years of follow-up in all the 27 patients that maintained their weight loss.

In conclusion, a comprehensive long-term clinical follow up was able to prevent weight regain in comparable levels of bariatric surgery, and could be an alternative whenever there is any barrier for the surgery. 



Cadegiani F. 5-Year Data of an Aggressive Pharmacological Approach to Moderate and Morbid Obesity: Is Prevention of Bariatric Surgery Feasible in the Long Run?. J Endocr Soc. 2020;4(Suppl 1):MON-LB101. Published 2020 May 8. doi:10.1210/jendso/bvaa046.2340 

Study Abstract

Background: Maintenance of weight loss in patients that undergo weight loss interventions is highly challenging, irrespective of the type of approach to obesity (whether surgical, pharmacological, or non-pharmacological). We proposed a protocol of an aggressive clinical treatment for obesity aiming to prevent the need of bariatric surgery, in patients unwilling to undergo this procedure, by proposing a protocol that included the combination of different anti-obesity medications and non-pharmacological modalities, for longer duration, and with an active approach to prevent weight regain. Our initial 2-year data showed that 93% (40 of 43 patients) with moderate and morbid obesity were able to avoid the need of bariatric surgery, with concomitant improvements of the biochemical profile. However, whether these patients would maintain their successful rates after five years was uncertain. Our objective is to describe the efficacy and safety of a long term (5-year data) pharmacological and multi-modal treatment for moderate and severe obesity. 

Methods: The 40 patients that were successful in the two-year approach in our obesity center (Corpometria Institute, Brasilia, DF, Brazil) were enrolled. A long-term anti-obesity protocol was employed, with continuous or intermittent use of anti-obesity drugs, trimestral body composition analysis, psychotherapy, visit to a nutritionist every four months, and both resistance and endurance exercises at least four times a week. Body weight (BW), total weight excess (TWE), body fat, markers of lipid and glucose metabolism, liver function, and inflammation were analyzed. Subjects that dropped out were considered as weight regain. Therapeutic success for the 5-year follow-up included as the maintenance of >20% loss of the initial BW loss, and no weight regain (or < 20% of the initial weight loss). 

Results: A total of 27 patients (67.5%) were able to maintain the body weight, seven dropped out, and six regained more than 20% of the initial weight loss. Of these, 21 (77.8%) had significant further increase of muscle mass and decrease of fat loss, while 17 (63.0%) had further weight loss (p < 0.05), compared to the 2-year data. Improvements on the biochemical profile persisted in all 27 patients, and had significant further improvements in 24 (88.9%) of these patients. 

Conclusion: The risk of weight regain five years after a weight loss treatment for obesity was significantly lower compared to previous literature, and comparable to the long-term outcomes of bariatric procedures. An aggressive, structured, and long-term clinical weight loss approach has been shown to be feasible, even for morbidly obese patients.



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