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Home » Uncategorized » Surgery is associated with better long-term outcomes than pharmacological treatment for obesity: a systematic review … – Nature.com

Obesity is defined as a BMI greater than or equal to 30 by the CDC and is currently among the most prevalent diseases in the world, in addition to being an important risk factor for many other diseases. It has high rates of morbidity and mortality21,22 and, in this context, weight loss can bring countless positive impacts to the individual. Currently, there are several treatments for obesity, and we can divide them into non-surgical or surgical.

Non-surgical treatments include non-drug and drug treatments. Among the non-medicated, we can highlight the change in eating habits, regular physical exercise, and cognitive behavioral therapy8. Ideally, these measures should be implemented for all patients living with obesity, even for those who will undergo drug or surgical treatment. Recently, in addition to lifestyle change, neuromodulation with deep transcranial stimulation has also been studied and has shown effectiveness in weight loss reduction23.

A systematic review carried out in 2021, which analyzed 64 articles concluded that among the most effective non-surgical interventions are low-carbohydrate or low-fat diets and combined therapies. This study also showed that non-drug interventions, such as physical exercise, when used alone, are not very effective in reducing the weight of these patients Therefore, a combination of two or more therapies should be chosen24.

Pharmacological treatment must be chosen together with the patient. One or more drugs can be used, the main ones used being: Liraglutide, Semaglutide, Tirzepatide, Orlistat, Phentermine and Sibutramine25.

Liraglutide was recently approved for the treatment of obesity and is now one of the most widely used drugs. It acts as a GLP-1 receptor agonist26,27,28, enhancing its effects. This group of drugs is already known in the treatment of Type 2 Diabetes Mellitus, a condition that can often be associated with obesity29,30, since its pathophysiology involves increased insulin resistance. The main actions of this drug are: increased satiety due to a reduction in the speed of gastric emptying, increased insulin release and decreased glucagon release. Semaglutide is a drug with a similar mechanism of action who demonstrated not only a substantial weight loss31, but was also associated with a lower 10-year T2D risk in people with overweight or obesity after 2years of follow up32. More recently, a new drug that combines GLP-1 and GIP receptor agonist, Tirzepatide, has shown even better results in the short term33.

Orlistat, in turn, reversibly inhibits the lipase enzyme34, which has the function of breaking down fat from food for its absorption, as well as inhibiting the absorption of ingested triglycerides. Thus, there is elimination of fat in the feces35. The main adverse effects are gastrointestinal symptoms, however this can be beneficial as it leads to a change in behavior, for example causing a lower consumption of foods rich in fat36.

Phentermine, an amphetamine analogue, can be used in conjunction with topiramate for the treatment of obesity. The mechanism of action of the drugs is not yet known, however, significant weight loss has already been observed, in addition to a reduction in the consumption of hypercaloric foods and a decrease in the speed of gastric emptying with the use of this combination of drugs37,38.

Sibutramine, widely used in the 1990s, acts to inhibit the reuptake of serotonin, norepinephrine, and dopamine34. Serotonin, in turn, activates POMC system neurons and inhibits NPY neurons, thereby promoting reduced appetite and increased satiety. Despite generating weight reduction39, some data show increased cardiovascular risk40, and therefore, it is no longer used as a first-line drug.

Among the possible surgeries, the most performed today are: Roux-en-Y Gastric Bypass (RYGB), Biliopancreatic diversion (BPD), Laparoscopic Sleeve Gastrectomy (LSG) and Laparoscopic Adjustable Gastric Band (LAGB). According to the NIH and the American Bariatric Society41,42, some indications for performing bariatric surgery are adults with BMI greater than or equal to 40 and adults with BMI greater than 35 accompanied by some comorbidity such as type 2 diabetes mellitus, obstructive sleep apnea or hypertension.

RYGB is one of the best-known procedures and its complications vary according to the surgical technique used. Some complications include gastric distention, ulcers, cholelithiasis, hernias, dumping syndrome, and hyperammonaemia encephalopathy.

BPD presents long-term nutritional complications, such as anemia, bone diseases and fat-soluble vitamin deficiency. This technique has high mortality rates, mainly due to the complexity of the technique.

Among the procedures described, LSG is the one with the fewest complications, being described in the literature bleeding or stenosis of the stoma. An alternative technique using endoscopy for sleeve gastroplasty has shown to be safe and efficient for weight loss after 104weeks, with important improvements in metabolic comorbidities43.

The procedure with the lowest mortality rate is the LAGB44. Despite this, it can present complications such as obstruction, band erosion, band slippage and gastric prolapse, esophagitis, hernia, in addition to having a high rate of reoperation, reaching 50% of patients who underwent this surgery45.

In this article, we compare data on weight loss through intensive drug treatment, which includes changes in eating habits, physical exercise, and medications, and through surgical treatment. Both treatments showed that weight loss caused an improvement in the lipid panel, with a reduction in total cholesterol, triglycerides and LDL, an increase in HDL, improvement in systolic and diastolic blood pressure, decrease in glycated hemoglobin and insulin resistance (accessed through HOMA), in addition to reducing the risk for cardiovascular diseases.

Our systematic review confirmed the findings of individual studies that bariatric surgery has a greater potential for weight reduction, BMI and waist circumference, as already described in individual articles and widely in the literature. It should be noted that even in the long term, this difference remained. Similarly, a 2014 Cochrane systematic review46 comparing RCT with more than 1year of follow-up showed that all 7 articles included demonstrated an advantage of the surgical group. An article47 on the use of pharmacological treatment for obesity showed that even recent drugs approved, including GLP 1 agonists, are not able to reduce weight to levels similar to those of bariatric surgery to date, despite the emergence of new drugs still in initial phase48. It is worth mentioning that in these studies the comparison time is relatively short (12months) and that we do not have data on the long-term impact. Thus, in relation to long term weight loss, bariatric surgery is still the best option.

Most articles were not able to individually demonstrate that surgical treatment is superior to non-surgical in terms of pressure reduction. However, the result of the meta-analysis showed a superiority of the surgical group in relation to both systolic and diastolic pressure, more pronounced in the BPD group. Wang49 performed a systematic review focused on the impact on pressure and demonstrated that there was a reduction in systolic and diastolic values, but the subgroup analysis showed that this occurs only in the RYGB groups for systolic pressure. Similarly, Schiavon also demonstrated a significant reduction in the need of blood pressure medication after 3years in the RYGB group when compared intensive medical treatment for obesity50. This difference found in only one subtype of surgery seems to be just a reflection of the sample size, which can be interpreted that surgical treatment in general tends to reduce pressure to a greater extent than non-surgical treatment. The fact that different types of surgery are significant may reflect the studies selected in our meta-analysis, which have longer follow-ups.

In relation to both HOMA-IR and glycated Hb, there was a more significant improvement in the group that underwent surgery. The way in which the data on diabetes remission was reported in the articles did not allow a meta-analysis to be carried out with these data and, therefore, it was not included. However, individual data from the Mingrone 2015, Mingrone 2021 and Schauer articles showed that the surgery group had better results. A network meta-analysis from 202151 comparing the different types of metabolic surgery for the treatment of obesity and diabetes showed that RYGB was 20% more likely to result in remission of type 2 diabetes compared to SG. There was no significant difference between the other groups. Moreover, the effects of bariatric surgery on diabetes is not exclusive for patients with obesity, as shown by a study with patients with a BMI of 2732kg/m2 that had a better glycemic control when treated with RYGB20. Regarding the lipid profile, Schauer's study was not able to demonstrate superiority in relation to LDL and HDL parameters. However, by combining the data from Mingrone's articles, it is possible to demonstrate that surgical treatment is superior. Regarding cholesterol reduction, Mingrone's studies showed that although RYGB and BDP were better in relation to non-surgical treatment, the BDP technique had a statistically greater reduction in relation to RYGB. This can be explained by the greater intestinal exclusion in BDP and, therefore, having a greater impact on lipid absorption. Despite Sayeed's study52 et al. was not included in this meta-analysis due to the inadequate way of separating the groups for analysis, the results regarding the lipid profile showed that the group that received both interventions was superior to the exclusive non-surgical treatment. It is important to point out that despite a statistically significant difference between the groups, the effect size of this difference is probably not clinically significant.

The choice of treatment for obesity can also have an impact on several other patient comorbidities. Hossain et al.53 performed a systematic review with 26 studies that showed that bariatric surgery appears to be more effective in the treatment of asthma. Similarly, a study by Crawford et al.15 showed that there is a greater increase in bone turnover in groups undergoing bariatric surgery in relation to pharmacological treatment. Other than that, bariatric surgery is also demonstrated to be superior in the treatment of other obesity related pathologies, such as Non-Alcoholic Steatohepatitis (NASH), and in the treatment of obesity in adolescents54,55.

The effect of major cardiovascular adverse events (MACE) and mortality56 have also been promising for bariatric surgery. A recent cohort comparing bariatric surgery in patients with obesity and use of GLP1-agonists inpatients with diabetes showed a lower risk of MACE in the surgical group57. The surgical treatment has also shown superiority when compared to medical treatment regarding the prevention of diabetic kidney disease in 5years for patients with diabetes and obesity58. Boyers et al. evaluated the cost-effectiveness of surgical and pharmacological treatment in the treatment of obesity and found that RYGB should be the treatment of choice only if the optimization of health system costs is considered59.

Another important consideration is the fact that pharmacological and surgical treatment for obesity are not mutually exclusive. Most clinicians choose to combine both treatment modalities in practice to improve results. Weight gain after bariatric surgery is a known possibility, and for those patients, two-thirds of the weight regain can be safely lost with GLP1 agonist, providing clinicians with a therapeutic option for this clinical challenge.

Despite the large number of articles in the literature on the treatment of obesity, there are few RCTs comparing non-surgical and surgical treatment, and most of them only follow up in the short term. In addition, many articles do not adequately describe the strategy used in non-surgical treatment. This lack of data and standardization in this type of treatment can lead to bias and possibly the formation of extremely heterogeneous groups for analysis.

Most of the studies included in our systematic review have diabetes as an inclusion criteria. In this circumstance, our findings may not be generalized to patients with obesity without diabetes.

Another important limitation of our systematic review refers to pharmacological treatment in the non-surgical group. The use of GLP 1 agonists has great potential in the treatment of obesity, but they have only started to be used recently. As the purpose of our article is to assess the long-term impact, there are still few articles available that used this drug. The use of the most recent medications, such as Tirzepatide, could not be evaluated in our study, once there are no RCTs in the literature presenting its long-term effects. Those drugs proved to be very efficient and might have similar effect in the long term. Future systematic reviews may reveal a different results when including the new generation of weight loss medication.

Finally, choosing the most appropriate treatment often involves individual characteristics of each patient, and the impact on quality of life can be extremely subjective and difficult to assess.

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Surgery is associated with better long-term outcomes than pharmacological treatment for obesity: a systematic review ... - Nature.com

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Home » Uncategorized » Surgery is associated with better long-term outcomes than pharmacological treatment for obesity: a systematic review … – Nature.com