In the last decade, the prevalence of obesity in the US has increased significantly, from 31% to 46%. However, the Brownstein et al.1 study observed a slight decrease for the first time in 2022 and 2023, raising hope for the treatment of this multifactorial disease that affects quality of life, decreases survival, and is associated with serious comorbidities.1 In addition to greater population awareness and certain lifestyle changes, 14% of the Americans studied had used GLP-1 agonists.1 Evidence about the effects of anti-obesity drugs is not homogenous, although GLP-1 analogues do appear to be effective. For instance, liraglutide 3.0 mg has a reported TWL (total weight loss) percentage of 7%–11%, while semaglutide 2.4 mg has provided a TWL of 15.8%. Tirzepatide, a GLP-1 and GIP agonist, has shown encouraging results in association with diet and lifestyle changes, with a TWL of 4%–25% in clinical trials (SURMOUNT-4), although only 50% of patients achieve 20% TWL after 72 weeks.3 Retratutide, another multi-agonist, has shown promising results with 5%–30% TWL in clinical trials, similar to other investigational drugs, but with no real-world results.4
When designing a treatment for obesity, it is essential to establish a %TWL goal that would improve comorbidities and the patient’s life expectancy.4 A TWL of 5% has been shown to be sufficient to improve high blood pressure and diabetes; 10% TWL benefits cardiovascular risk, OSA, and MAFLD; however, only 20% TWL is able to reducing the incidence of cancer, kidney disease, and mortality.5 Metabolic and bariatric surgery (MBS) has demonstrated the most consistent efficacy to date, with reports of 20%–30% TWL with sleeve gastrectomy and a 25%–40% TWL with gastric bypass. In 75%–80% of patients, surgery achieves the target weight loss of 20% TWL, which improves survival, cancer risk, kidney disease, diabetes, and cardiovascular risk.4,5 The results from clinical trials of new third-generation anti-obesity drugs are encouraging. Today, however, the biggest problems with these treatments are the high rate of weight gain upon discontinuation of treatment and the withdrawal rate due to gastrointestinal symptoms.6 Therefore, these drugs are still not a competitive alternative to MBS, which is already called one-shot therapy, especially considering the medium-term cost, with a high cost-effectiveness ratio of $72 962/QALY (quality-adjusted life year) for semaglutide compared to $3000/QALY for gastric bypass.7,8
The combination of drugs before and/or after MBS has raised great expectations and has even been the subject of a position statement issued by the IFSO (International Federation for the Surgery of Obesity). The publication acknowledges that there is little scientific evidence about this combination, but there are studies with positive results that encourage further research on the topic and recommend it to certain patients.2,9
The combination of anti-obesity drugs with diet and exercise has shown good results for preoperative weight loss prior to MBS, especially in severely obese patients with a BMI greater than 50 kg/m or those at high surgical risk.10 Semaglutide has shown greater efficacy than liraglutide, and both have been more effective than very-low-calorie diets alone for preoperative weight loss prior to MBS, but they are less effective than the intragastric balloon.11
Similarly, the use of anti-obesity drugs in certain patients after MBS is currently presented as a good option.9 We know that, despite the high effectiveness of MBS, a percentage of patients (approximately 20%–25%)12 either do not achieve their weight loss goals or regain weight after surgery. The early use of GLP-1 analogues is recommended in patients who have not achieved the expected goal to improve the %TWL and its beneficial effect on comorbidities.9
In recent years, several systematic reviews and meta-analyses have been published on this topic. In their 2024 systematic review analyzing 8 studies (557 patients), Dutta et al.12 showed that semaglutide is superior to liraglutide in terms of post-MBS weight loss after 6 and 12 months of treatment. Esparham et al.,13 in their systematic review and meta-analysis of 19 studies, concluded that GLP-1 analogues are a safe and effective treatment in cases of weight regain or insufficient weight loss after MBS. They showed that semaglutide 2.4 mg weekly achieves significantly greater weight loss compared to liraglutide 3 mg daily, with a mean difference of 4.15 kg and mild gastrointestinal side effects. To date, few randomized clinical trials have been published evaluating the use of these drugs after MBS. Both the studies by Mok et al.14 and Thakur et al.15 show optimistic results using liraglutide 3 mg/day versus placebo after MBS (the former in patients with inadequate weight loss, and the latter starting 6 weeks after the procedure).
In conclusion, obesity treatment requires a multimodal approach that combines lifestyle changes, pharmacotherapy, and bariatric and metabolic surgery. Although new anti-obesity drugs have shown promising results, they are still not as effective and cost-effective as surgery. Nonetheless, their preoperative use can optimize surgical outcomes in patients with extreme obesity, and their postoperative use is a valid option in cases of insufficient weight loss or weight regain.9
GLP-1 analogs have proven useful in these settings, but further clinical trials are needed to establish their definitive role in conjunction with the surgical treatment of obesity.9 Undoubtedly, the key to success will lie in the strategic combination of all available tools to maximize efficacy and improve long-term outcomes.
FundingThis study has received no funding of any kind.
The authors have no conflict of interests to declare.
