The objective of supplement #2 is to focus on treatment with topics including pharmacotherapy, bariatric surgery, and the challenges with obesity as a chronic disease and weight regain. The format of this section will be case-based and aims to deliver the evidence in a narrative way that leverages the authors’ and editors’ extensive clinical experience.
All articles published in DPG Open Access journals
This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).
Dr. Megha Poddar is an endocrinologist and obesity medicine specialist in Toronto, Ontario. She has been a diplomate of the American Board of Obesity Medicine since 2016 and is an assistant professor (adjunct) in the Department of Medicine at McMaster University.
She has a multidisciplinary, team-based approach to obesity management which encompasses all 3 modalities of treatments including behavioural counselling, medications and surgical treatments. Dr. Poddar is the clinical director of the LMC Weight Management Program and the medical director of the Medical Weight Management Centre of Canada (MWMCC) which delivers evidence based behavioral and medical treatment for obesity.
Dr. Poddar is the lead author on multiple resources for obesity education including the Obesity section of the McMaster textbook of internal medicine and is a co-author of the Assessment chapter of the 2020 Canadian Adult Obesity Clinical Practice Guidelines. She is also a principal investigator in randomized control trials in type 2 diabetes and obesity. She is a mentor for obesity management and clinical development for healthcare providers both nationally and globally and is passionate about advocating for patients living with obesity.
Dr. Maria Tiboni is an internist-hospitalist and obesity specialist. She has been appointed associate professor in the department of Medicine at McMaster University. Dr. Tiboni sits at the Ontario Advisory Board for the Ontario Bariatric Network and is a diplomate of the American Board of Obesity Medicine.
Dr. Tiboni has been the medical lead at the St Josephs Health Care Bariatric Center of Excellence in Hamilton, Ontario since its inception. Her main focus is in the perioperative care of patients undergoing metabolic surgery including patient selec-tion, pre-operative optimization, post operative care and management of medical complications arising following metabolic surgeries.
Dr. Tiboni is passionate about teaching and education. She is the Director of the McMaster University Metabolic and Bariatric Fellowship Program. Dr. Tiboni participates actively in research in the field of obesity and is a strong advocate of patients living with obesity.
(Objective: Review the Available and Upcoming Options, Discuss the Algorithm in the Clinical Practice Guidelines Re: Patient Selection)
Marissa is a 45-year-old woman who has been referred to you for obesity management. She reports having lived with obesity for much of her life. She gained weight during each of her two pregnancies and was unable to get back to her pre-pregnancy weight. She gained another 20 pounds during the pandemic, when she initially lost her job and has been working from home for most of the time over the last two years. She currently takes no medications. Her surgical history is only significant for tubal ligation. She has tried numerous dietary and lifestyle-based interventions to lose weight. These include medical nutrition therapy comprising of caloric restriction and running on her treadmill for 45 -minutes, 5 days per week over the last 6 months. She lost 7 kg from her starting weight of 112 kg but her weight seems to have plateaued and she is frustrated about her inability to lose more weight despite her best efforts.
Her current weight is 105 kg, with a body-mass index (BMI) of 37.2 kg/m2. At her last annual physical, her blood pressure was within targets, and there were no signs of syndromic obesity. Her baseline blood work was notable for a glycated hemoglobin of 6.1%, but she otherwise had a normal metabolic profile. A screening ultrasound showed evidence of fatty liver disease. She is interested in learning more about pharmacotherapy for weight management and has the -following questions.
Which therapy would be best suited for me?
How much weight should I expect to lose through this therapy?
How long would I have to take medication?
Obesity is a common medical condition and affects up to 8.2 million Canadians 18 years or older.1 While the prevalence of obesity in Canada has risen by three-fold since 1985, more worryingly, the prevalence of those living with class II (BMI > 35–39.9 kg/m2) and class III (BMI > 40.0kg/m2) obesity increased by more than 4 and 5-fold during this same time. This has negative implications for overall health as obesity has been linked to other major chronic medical conditions including diabetes, cardiovascular disease, obstructive sleep apnea, depression, anxiety and various cancers. It has also been associated with increased mortality and reduced life expectancy by 2–4 years in those with class I obesity (BMI > 30–34.9kg/m2) and by 8–10 years in those with class III obesity.
Given its detrimental impact on overall health and associated increased mortality, obesity is considered a chronic disease by the Canadian Medical Association.2 The latest Obesity Canada guidelines recommend using pharmacotherapy for obesity management in those with obesity (BMI >30 kg/m2) and in select patients with a BMI >27 kg/m2 and adiposity--related complications including obstructive sleep apnea, type 2 diabetes, hypertension, and dyslipidemia. Despite this, pharmacotherapy remains underutilized as a treatment for obesity, with some estimates suggesting that up to 98% of individuals who would be eligible to receive pharmacotherapy do not receive it, in comparison to those with type 2 diabetes, where most patients who are eligible for appropriate treatment with pharmacotherapy are offered and prescribed this treatment. The causes of this treatment-care gap are numerous. They include but are not limited to the lack of appreciation of obesity as a chronic medical condition, concerns regarding side effects of previously used anti-obesity medications (AOMs), lack of access to these medications, and mistaken notions regarding the time course of treatment. However, recent data has shown promise regarding the safety and efficacy of the pharmacotherapy options for obesity management and should be considered along with the 2 other pillars of obesity management, behavioural therapy, and bariatric surgery. Currently, four medications are approved for managing obesity in Canada. These include orlistat, naltrexone-bupropion combination, liraglutide, and semaglutide. We will review the evidence regarding the mechanisms of action, efficacy, side effect profile, and specific comorbidities, suggesting using one agent over another for each option.
Orlistat is the oldest available medication among the four approved options for weight management in Canada. It is a hydrogenated lipstatin derivative and works as an inhibitor of pancreatic lipase. However, in general, it has not been used as a first-line treatment for various reasons, the most important of which is that it does not target the pathophysiology of obesity. Given that obesity is a chronic disease mainly centered in the brain (hypothalamus, mesolimbic, frontal lobe pathways), orlistat does not target any of these areas but focuses primarily on malabsorption at the gut level.
In a randomized control trial, at a dose of 120 mg three times a day, orlistat was associated with a net 2.9% weight loss compared to a low-fat, low-calorie diet. Thirty-five percent of those in the orlistat group lost at least 5% of their body weight, while 28% lost up to 10%. Results of a meta-analysis comprising 16 studies involving orlistat demonstrated a placebo-subtracted weight loss of 2.9% with orlistat compared to placebo. In addition, there were modest improvements in glycemic control, blood pressure, and low-density lipoprotein (LDL) cholesterol levels. However, given its mechanism of action, it is not surprising that orlistat is associated with gastrointestinal side effects, including steatorrhea and fecal urgency which can occur in up to 15–30% of participants.
Due to these side effects, the six months, one-year, and two-year adherence rates with orlistat remain quite low at 18%, 6%, and 2%, respectively. Orlistat is also associated with impaired absorption of fat-soluble vitamins A, D, E, and K. Among these, impaired vitamin K absorption may affect patients taking warfarin. In addition, poor absorption of medications, including levothyroxine, cyclosporine, and anticonvulsants, may be seen, suggesting the importance of close clinical and biochemical monitoring for patients taking these medications. It is contraindicated in those with chronic malabsorption syndromes and cholestasis and has been associated with rare cases of oxalate nephropathy and liver failure. Due to a lack of clear benefits and the potential for fetal harm, it is not recommended for patients during pregnancy or breastfeeding.
Owing to the modest effects on weight loss, side effect profile, lack of target within the central nervous system and more effective options, it is seldom used as first line agent for obesity management. However, in certain patients, this may still be a helpful option, namely those who struggle with chronic constipation or difficult to treat hyperlipidemia. It is also the lowest cost option for those paying out of pocket and its use should be assessed on a case-by-case basis.
Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that is effective for glycemic control, weight management, and reducing the risk of cardiovascular events in high-risk patients with type 2 diabetes. Its primary role in weight management seems to be mediated by its effect of increasing satiety through its central impact on the pro-opiomelanocortin (POMC)/CART neurons and by delaying gastric emptying. While the near-maximal anti-hyperglycemic effects of liraglutide is achieved at a dose of 1.8 mg subcutaneously (sc) daily, the 3 mg per day dose is recommended for weight management.
The SCALE study was a randomized controlled trial assessing liraglutide 3.0 mg daily for weight management in participants without diabetes. The results showed that liraglutide was associated with a 5.4% placebo-subtracted weight loss, with 63.2% and 33.1% losing >5% and >10% total body weight over one year, respectively. Long-term studies demonstrated sustained weight loss with liraglutide over 3 years with a net difference of 4.3% total body weight loss over 3 years compared to placebo. In this study, there was also a positive result showing the delay in the progression of prediabetes to type 2 diabetes by 2.7-fold compared to those in the placebo group. Amongst those with type 2 diabetes, liraglutide 3mg/day had a mean weight loss of 4% compared to liraglutide 1.8 mg/day, with a mean weight loss 2.7%. In terms of other comorbidities related to weight, there was a statistically significant reduction in systolic and diastolic blood pressure, -2.87 mmHg and -0.73 mmHg, respectively, and a reduction of -0.08 mmol/L in LDL with liraglutide 3.0 mg/day compared to placebo. Given that liraglutide has shown cardiovascular benefit in high-risk patients with type 2 diabetes, the Obesity Canada guidelines have extrapolated this data to suggest cardiovascular safety with liraglutide 3.0 mg/day for weight management. Resolution of NASH and improvement in steatosis were also seen, which is a significant outcome given the high prevalence of NASH and the lack of effective available treatment options. Lastly, the IWQOL and SF-36 questionnaires in the SCALE trials consistently improved quality of life data.
The most common side effects are gastrointestinal, including nausea, constipation, heartburn, and vomiting. However, these are usually mild and occur mainly during titration, as seen with most other GLP1 RAs. Due to these side effects, a slow titration of 0.6 mg sc daily, with an increase of 0.6 mg weekly, if tolerated, until the maximum dose of 3 mg daily is usually recommended. There is an increased risk of gallstones and increased risk of pancreatitis. However, half of these cases were associated with gallstones, and the risk is generally considered low. Liraglutide is contraindicated in those with a personal or family history of medullary thyroid cancer (MTC) or associated syndromes, including Multiple Endocrine Neoplasia-2 (MEN-2) due to an increased risk of MTC seen in rodent studies, a risk which has so far not been seen in human studies. Like all other agents for obesity management, it is also contraindicated during pregnancy and breastfeeding.
There is an emerging role for liraglutide in patients after bariatric surgery, with multiple studies demonstrating efficacy in glycemic control and weight loss. In an unpublished report involving patients who had initially lost 25% of their weight following Roux-en-Y gastric bypass (RYGB) but subsequently regained 10% of their weight, 3.0 mg dose of liraglutide was associated with 9.7% loss of weight compared to 1.8% for those in the placebo group. Fortunately, the rates of gastrointestinal side effects were similar compared to other trials involving the use of liraglutide and in those without a history of bariatric surgery.
The effects of liraglutide on weight loss, like all other AOMs, are only present while on continued treatment. This was seen in a trial demonstrating that stopping liraglutide after 160 weeks of treatment was associated with partial weight regain. As mentioned previously, while the net weight loss was 4.3% compared to the placebo in the treatment group at 160 weeks, it was reduced to 3.1% over 12 weeks following cessation. This underscores the need for continued treatment to maintain the weight loss benefit achieved due to liraglutide and highlights that obesity, like other chronic diseases, requires long-term treatment.
Like liraglutide, semaglutide is also a GLP-1 receptor agonist, is effective as an anti-hyperglycemic agent, and reduces cardiovascular risk primarily in those with pre-existing cardiovascular disease at the 1 mg per week dose. Its mechanism of action is similar to that of liraglutide, except that its longer half-life allows for once-weekly dosing, compared to liraglutide which is given once daily. The 2.4 mg/week dose was recently approved by Health Canada in 2021 for weight management in those without diabetes under the name “Wegovy’; however, is not yet available at the time of writing this supplement.
Semaglutide 2.4 mg was associated with a 16% weight loss compared to 5.7% in placebo in the STEP1 randomized controlled trial. 86.4% of participants experienced >5% weight loss, while 69.1% experienced >10% weight loss. Among those with type 2 diabetes, 9.6% weight loss was observed in those taking the 2.4 mg weekly dose, compared to 6.99% in those on the 1 mg weekly dose versus 3.4% in the placebo group. Among those with prediabetes, 2.4 mg semaglutide led to normoglycemia in 84.1% of participants compared to 47.8% in the placebo. More recently, semaglutide 2.4 mg/week has also been compared to liraglutide 3.0 mg/day in those without diabetes. Over the 68 weeks study, semaglutide 2.4 mg was associated with an additional 9.4% weight loss compared to 3 mg daily dose of liraglutide.
In the updated Canadian obesity clinical practice guidelines, there has been a strong focus on moving away from weight loss goals and improving specific comorbidities related to weight. This emphasis also serves as a practical guide to help understand which patients would be better suited for specific pharmacotherapy option(s). A summary table is provided in the pharmacotherapy chapter of the clinical practice guidelines and is reproduced below. Semaglutide 2.4 mg per week has been shown to improve most metabolic comorbidities, including but not limited to systolic and diastolic blood pressure, total cholesterol, triglycerides, HbA1c, and NASH. It has also shown positive results in improving quality of life measures, including the IWQOL and SF-36 questionnaires. No cardiovascular outcome trials have yet been completed in obesity treatments, however, the SELECT trial is the first cardiovascular outcome trial trial in obesity, looking at semaglutide 2.4 mg per week in patients with overweight and obesity and is due to be completed at the end of 2023.
The most common side effects are gastrointestinal, including nausea, constipation, diarrhea, and vomiting like most other GLP1RAs. Cases of acute pancreatitis and gallstones are rare. Given the association between GLP-1 receptor agonists and medullary thyroid carcinoma in rodent studies as described above with liraglutide, semaglutide is also contraindicated in patients with a personal or family history of MTC or MEN-2 syndrome. Most gastrointestinal side effects can be mitigated with slower titration; however, the recommended starting dose of semaglutide is 0.25 mg weekly for 4 weeks, which can be titrated up to 0.50 mg, 1 mg, 1.7 mg, and finally, 2.4 mg sc weekly doses each over 4 weeks, as tolerated.
Like liraglutide, the effects of semaglutide on weight loss were also partly reversible following cessation of treatment. For example, in participants who took semaglutide for 68 weeks and lost 17.3% of their starting weight, treatment cessation was associated with an 11.6% weight regain, leading to an attenuation of the treatment effect and net weight loss of 5.6% over 120 months. This is an important teaching point for patients when starting AOMs, as patients who accept that obesity is a chronic medical condition are more likely to adhere to long term treatment.
Naltrexone/bupropion (Contrave) is a combination medication that incorporates naltrexone. This opioid antagonist has been used for decades for alcohol misuse and opioid dependence, with bupropion, a norepinephrine and dopamine reuptake inhibitor, used for depression and smoking cessation. This combination treatment, when used in a sustained-release formulation with a target dose of 32 mg of naltrexone and 360 mg of bupropion daily, is thought to influence the mesolimbic reward system to help curb cravings by dampening the reward/pleasure signals through the dopamine pathway and also acts directly on the hypothalamus to induce satiety (Figure 1). It was approved as an AOM and has been available in Canada since 2018.
Figure 1. Mechanism of action of naltrexone/bupropion.
In the randomized control trial (COR-1) examining naltrexone/bupropion versus placebo, naltrexone/bupropion was associated with a 6.1% weight loss compared to 1.3% in the placebo group over one year in those without diabetes. In this study, 48% of the participants in the treatment group experienced >5% weight loss, while 25% had >10% weight loss. Among those with diabetes, 5% weight loss was experienced by those in the treatment group versus 1.8% in the placebo group. This is a helpful parameter to understand a realistic goal for our patients, but remember that a modest weight loss of 5–10% has improved metabolic comorbidities related to weight.
Naltrexone/buproprion has a unique mechanism of action compared to GLP RAs and, for this reason, can be helpful specifically in a patient population that reports higher rates of cravings or activated reward/pleasure-seeking behaviours associated with food. The control of eating, craving control, positive mood, and cravings for sweet and savoury foods questionnaires all showed a positive response in the randomized control trials with Contrave, however, did have less of a robust effect on improving metabolic comorbidities related to weight compared to GLP1RAs.
The most common side effects experienced by patients on naltrexone/bupropion include nausea, constipation, headache, dry mouth, dizziness, and diarrhea. Due to this, a slow titration is again recommended with the starting dose as 1 tablet comprising 8 mg of naltrexone and 90 mg of bupropion daily in the morning and increasing the dose by one tablet every week until the target dose of 2 tablets twice daily is reached. There are several contraindications to using this combination medication, including a history of uncontrolled hypertension, seizure disorder, eating disorders including anorexia or bulimia nervosa, abrupt discontinuation of alcohol, antiepileptics, and concomitant use of opioids, monoamine oxidase inhibitors and of course pregnancy and lactation. Patients with suicidal ideation should also not be prescribed this medication given concerns that, in general, antidepressants can increase the risk of suicidal ideation, especially initially after starting treatment. Since bupropion inhibits the hepatic CYP2D6 system, caution should be used in prescribing this agent in those taking other medications metabolized by the same system, including serotonin selective reuptake inhibitors, beta-blockers, anti-psychotic agents, tricyclic antidepressants, and some antiarrhythmics. Since bupropion is metabolized by the CYP2B6 system, it should not be used above one tablet twice daily dose in those taking CYP2B6 inhibitors, including clopidogrel, and avoided in those taking CYP2B6 inducers, including ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, phenytoin. A summary of pharmacotherapy options approved in Canada 2022 is outlined in Table 1.4
Table 1. Pharmacotherapy for Obesity Management
| Orlistat | Liraglutide | Naltrexone/Bupropion | Semaglutide | |
|---|---|---|---|---|
| Mode of administration | Oral | Subcutaneous | Oral | Subcutaneous |
| Dose/frequency | 120 mgTID | 3.0 mg daily | 16/180 mg BID | 2.4 mg weekly |
| Effect on % weight loss at 1 year, placebo subtracted | −2.9%a | −5.4%2 | −4.8%5 | −12.5%1 |
| Effect on weight over longer term, placebo subtracted | −2.8 kg at 4 years8 | −4.2% at 3 years* | Not studied | Not available |
| % of patients achieving ≥ 5% weight loss at 1 year | 54% (vs. 33% in placebo)28 |
63.2% (vs. 27.1% in placebo)2 |
48% (vs. 16% in placebo)5 |
86.4% (vs. 31.5% in placebo)1 |
| % of patients achieving ≥ 10% weight loss at 1 year | 26% (vs. 14% in placebo)28 |
33.1% (vs. 10.6% in placebo)2 |
25% (vs. 7% in placebo)4 |
69.1% (vs. 12% in placebo)1 |
| % of patients achieving ≥ 15% weight loss at 1 year | Not studied | 14.4% (vs. 3.5% with placebo)* |
13.5% (vs. 2.4% with placebo)* |
50.5% (vs. 4.9% with placebo)1 |
| % of patients achieving ≥ 20% weight loss at 1 year | Not studied | Not studied | Not studied | 32% (vs. 1.7% in placebo)1 |
| Effect on maintenance of previous lifestyle-induced weight loss | 2.4 kg less weight regain vs. placebo over 3 years7 | −6.0% additional placebo-subtracted weight loss at 1 year4 | Not studied | Not studied |
| Cost | $$ | $$$$ | $$$ | Unknown |
| Contraindications | •Cholestasis •Chronic malabsorption syndrome •Pregnancy, attempting conception, breastfeeding |
•Personal or family history of medullary thyroid cancer •Personal history of MEN2 syndrome •Pregnancy, attempting conception, breastfeeding |
•Uncontrolled hypertension •Any opioid use •History of, or risk factors for. seizure •Abrupt discontinuation of alcohol •Concomitant administration of monoamine oxidase inhibitors •Severe hepatic impairment •End-stage renal failure •Pregnancy, attempting conception, breastfeeding |
•Personal or family history of medullary thyroid cancer •Personal history of MEN2 syndrome •Pregnancy, attempting conception, breastfeeding |
| Common side effects | Loose, oily stools, flatus | Nausea, constipation, diarrhea. vomiting | Nausea, constipation, headache, diy mouth, dizziness, diarrhea | Nausea, diarrhea, constipation, vomiting |
| Rare side effects | •Liver failure •Nephrolithiasis •Acute kidney injury |
•Cholelithiasis •Pancreatitis |
•Seizure •Worsening of depression |
•Cholelithiasis •Pancreatitis |
| Medication interactions | •Fat-soluble vitamins •Levothyroxine •Cydosponne •Oral anti-coagulants •Anti-convulsants |
May affect absorption of medications due to slowing of gastric emptying | Yes: See chapter text | May affect absorption of medications due to possible slowing of gastric emptying |
Table 2. Pharmacotherapy for Obesity: Effects on Adiposity-Related Comorbidities
| Orlistat | Liraglutide 3.0mg | Naltrexone/Bupropion | Semaglutide 2.4mg | |
|---|---|---|---|---|
| Effect on prediabetes | 37.3% reduction in risk of developing T2DM over 4 years8 | 79% reduction in risk of developing T2DM over 3 years3 | Not studied | Not available |
| Effect on BP at 1 year, placebo subtracted | −1.7 mm Hg SBP −0.71 mmHg DBP37 |
−2.87 mm Hg SBP −0.73 mmHg DBP38 |
Not significantly different37 | −5.1 mm Hg S8P −2.4 mm Hg DBP1 |
| Effect on lipids at 1 year, placebo subtracted (only statistically significant changes in lipid parameters listed) | LDL −0.22 mmol/L HDL +0.03 mmol/L37 |
LDL −0.08 mmol/L38 | HDL +0.06 mmol/L37 | Total chol −0.22mmol/L LDL −0.1 mmol/L HDL +0.1 mmol/L Triglycerides −0.22 mmol/L1,39 |
| Effect on HR at 1 year, placebo subtracted | No change | +2.4 BPM2 | +1.1 BPM5 | +4.2BPM1 |
| Effect on A1C in patients with diabetes at 1 year, placebo subtracted | −0.4%12 | −1.0%10 | −0.5%11 | −1.2%9 |
| Effect on MACE | Not studied | Cardiovascular safety demonstrated40 | Not studied | Not available |
| Effect on NASH | No change | Resolution of NASH and improvement in steatosis (39% with lira 3 mg vs. 9% with placebo)14 | Not studied | Resolution of NASH (59% with semaglutide 0.4 mg daily vs. 17% with placebo)15 |
| Effect on PCOS | Not studied | Not sufficiently studied | Not studied | Not studied |
| Effect on OA | Not studied | No benefit | Not studied | Not available |
| Effect on OSA (placebo subtracted) |
Not studied | Reduces AHI by 6/hour13 | Not studied | Not studied |
| Effect on physical function | Not studied | SF-36 – Improvement41 IWQOL – Improvement41 |
IWQOL – Improvement4 | SF36 – Improvement1 IWQOL – Improvement1 |
| Effect on QoL | Not studied | SF36 – Improvement41 IWQOL – Improvement41 |
IWQOL – Improvement4 | SF36 – Improvement1 IWQOL – Improvement1 |
| Effect on CoEQ (cravings) | Not studied | Not studied | Improvements in craving control, positive mood, craving for sweet and savoury food42 | Improvements in craving control, positive mood, craving for sweet and savoury food43 |
Your assessment: Marisa is a 45-year-old patient with class II obesity and EOSS Stage 1.
After reviewing the pathophysiology of obesity as a chronic disease, reviewing and addressing internalized weight bias, and completing a full obesity assessment, Marisa wished to discuss pharmacotherapy for weight management. Since Marissa has a BMI of >30 kg/m2, she meets the criteria for starting a pharmacologic agent for treating obesity, and we reviewed all the different options with her today. Based on Obesity Canada pharmacotherapy decision tool, she would be a good candidate for consideration of pharmacotherapy. You discuss the options of considering orlistat or a GLP-1 receptor agonist (liraglutide or when available, semaglutide) given that she has prediabetes and fatty liver disease. In case of cravings, depression, or smoking, naltrexone-bupropion could be recommended. However, in her case, a GLP-1 receptor agonists with benefits in preventing progression to type 2 diabetes and improved NASH would likely be her best option (Figure 2).
Figure 2. Pharmacotherapy decision tool.
*Medications approved in Canada as of June 2022: Liraglutide 3 mg daily, Naltrexone/Bupropion 16/180 mg bid, Orlistat 120 mg tid, Semaglutide 2.4 mg weekly; **Treatment of comorbidities, percentage and durability of weight loss; ***Including cost, frequency, route of administration and tolerability
She asks about the expected weight loss with GLP-1 receptor agonists. You advise her that liraglutide is associated with a 5.4% net loss of weight compared to placebo, and with semaglutide patients experience a net loss of 10.3% weight compared to placebo, typically in addition to a 3–5% seen with behaviour changes. Her goal is to lose at least another 10% of her weight. You advise her that the proportion of patients losing >10% of their starting weight is 33.1% on liraglutide but 69.1% on semaglutide. However, you informed her that the 2.4 mg weekly dose is unavailable in Canada. She checked with her insurance plan, and unfortunately, semaglutide 1 mg/week is available but only covered for those with type 2 diabetes. You also have a detailed discussion with Marisa reviewing the pathophysiology of obesity and the complex interplay between non-modifiable risk factors, including her biology, genetics, and neurohormonal profile. Moving away from weight-based goals and towards health-based, functional, behavioural goals is more effective in helping with long-term motivation. You review the concept of achieving her “best weight,” the weight that a person can achieve and maintain while living their healthiest and happiest life and ensure her that she will be continued to be supported towards improving her individual goals.
Based on the superiority of semaglutide versus liraglutide, and the once-weekly versus once-daily dosing for the former versus the latter, respectively, Marissa says she prefers semaglutide. However, there are important practical considerations. AOMs are not covered by any public health program in Canada. Marissa is fortunate to have private health insurance, but her benefits do not cover semaglutide at the dose needed for obesity treatment and is not yet available in Canada. However, it covers liraglutide 3.0 mg daily dose, a Health Canada-approved option for obesity.
Given this information, she was agreeable to proceeding with liraglutide. She knew this was a daily injectable and was intended to be long-term therapy. You reviewed the prescription and titration with her in detail and discussed the side effects and how to mitigate these with a slower titration. She is aware of booking an appointment with her pharmacist to review the injection technique and is also provided additional resources like injections videos. She was advised regarding a patient support program to help access allied health care through the industry provider.
She was somewhat dismayed that she would have to take this medication long-term since there is a concern regarding weight regain after stopping the medication. You provided an analogy that obesity is a chronic disease, much like other diseases, including type 2 diabetes, hypertension, and dyslipidemia, and requires ongoing medical treatment to control the condition. In her case, controlling her obesity could potentially also reduce the risk of developing type 2 diabetes, which can be a complication of obesity. She is agreeable and sets up a follow-up appointment to review her progress. Lastly, you can review with her that the most weight benefit that occurs with pharmacotherapy is in the first 3–6 months of treatment with the maximally tolerated dose. A follow-up is booked in 3 months to reassess.
Obesity is a chronic medical condition for which safe and effective pharmacotherapy treatment options are available. Unfortunately, due to multiple factors, including lack of awareness, stigma, bias toward obesity, and lack of access/funding for these treatments, they remain underutilized. Despite this, patients are starting to advocate for their own health and are approaching their doctors for support. Exciting new therapeutic options, including combination treatments with Glucose-dependent insulinotropic -polypeptide-1 (GIP-1) /GLP1-RA and amylin/GLP1-RA are underway in phase 3 studies and have shown promise for higher rates of therapeutic efficacy and, more importantly, more options for our patients struggling with obesity.
It is crucial to individualize treatment, keeping in mind factors including the patients’ choice, medication access, and comorbidities, especially as more medications become available. It is equally important to inform them of the expected weight loss, side effect profile, and dissipation of effect following cessation to assist them in choosing the best medication for them and help with long-term motivation. Further studies are needed to help guide the individualization of therapy and to understand the beneficial effects of combination therapy on weight management.
Obesity Canada. Canadian Adult Clinical Practice Guidelines. Obesity Canada. Accessed Nov 15, 2022. Available at: https://obesitycanada.ca/guidelines/chapters
Pi-Sunyer X et al. SCALE Obesity and Prediabetes NN8022-1839 Study Group. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med. 2015 Jul 2;373(1):11–22. https://doi.org/10.1056/NEJMoa1411892. PMID: 26132939.
Wilding JPH et al; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar 18;384(11):989–1002. https://doi.org/10.1056/NEJMoa2032183. Epub 2021 Feb 10. PMID: 33567185.
Greenway FL et al; COR-I Study Group. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo--controlled, phase 3 trial. Lancet. 2010 Aug 21;376(9741):595–605. https://doi.org/10.1016/S0140-6736(10)60888-4. Epub 2010 Jul 29. Erratum in: Lancet. 2010 Aug 21;376(9741):594. Erratum in: Lancet. 2010 Oct 23;376(9750):1392. PMID: 20673995.
(Objective: Discuss the Different Types of Surgery, the Clinical Criteria and How To Pick To the Right Patient).
Anne is a 47-year-old librarian who has been referred for assessment and management of obesity with associated comorbid conditions. She has struggled with weight gain since late puberty and has steadily gained weight over many years, but this has worsened in the last decade since her mobility declined due to back pain. She has been to multiple commercial weight loss programs in the past and successfully lost 60–70 pounds twice but unfortunately regained all the weight both times. Her medical history is relevant for type 2 diabetes which is suboptimally controlled on insulin with established nephropathy. She has hypertension and dyslipidemia, well controlled on medication. She is bothered by occasional gastroesophageal reflux disease (GERD) and has moderate obstructive sleep apnea (OSA) requiring continuous positive airway pressure. She has severe osteoarthritis (OA) of the knees and chronic back pain which limits her ability to be as active as she would like, and she is currently using a walking aid for long walks. Currently, Anne’s weight is 127 kg, her height is162 cm, and her BMI is 48.4 kgm2. This was her highest adult weight.
Anne is very motivated and is looking forward to discussing weight loss surgery. She has already enrolled in an exercise program at a local pool, is starting to choose healthier foods/snacks, and has seen a positive benefit to these changes with improved blood sugar control. Anne takes metformin 1 g twice daily, semaglutide 1 mg sc weekly, empagliflozin 10 mg daily, and insulin levemir 100 U twice daily with novorapid 15–20 U at mealtime for her diabetes regimen. She also takes perindopril 8 mg daily, indapamide 1.25 mg daily, citalopram 40 mg daily, rosuvastatin 20 mg daily, atenolol 50 mg daily and pantoprazole 40 mg daily for her other comorbidities. She has no allergies. She had an uncomplicated laparoscopic appendectomy in childhood.
She lives with her husband, does not smoke, and seldom drinks alcohol (1 glass at social events). She is on disability due to her back pain and obesity. Her family history is relevant as her mother had a myocardial infarction at age 60 and her father and brother have diabetes and obesity. Recent investigations showed fasting blood glucose of 10 mmol/L, HBA1c of 8.4%, mildly elevated liver enzymes, normal -creatinine and glomerular filtration rate. However, her urine albumin/creatinine was above target at 3.5. The ultrasound of her liver showed hepatomegaly from severe fatty infiltration.
Anne would like to lose weight to see improvement in her medical conditions, gain mobility and improve her quality of life. She heard about the benefits of metabolic surgeries from a friend, but she also heard people saying that surgery was an easy way out and most people regain the weight after surgery. Deep down, Anne believes that if she just tried harder and did all the right things, she might be able to lose weight on her own. She is interested in learning more about bariatric surgery for weight management and has the following questions:
Is bariatric surgery an option for me?
What should I expect from surgery?
What type of surgery is best for me?
Eligibility criteria for metabolic surgery in Canada is guided by the National Institutes of Health (NIH) guidelines devised in the 1990s. Patients with a BMI > 35 kg/m2 with adiposity--related comorbidity (hypertension, diabetes, OSA, GERD, etc.) or a BMI > 40kg/m2 meet the criteria for metabolic surgery. Patients should be motivated and agreeable to long term follow up to achieve long term success and have an acceptable surgical risk. There are very few absolute contraindications to metabolic surgeries, including active cancer with poor prognosis, unstable psychiatric disease, and alcohol/drug dependency. Relative contraindications include portal hypertension, smoking status and advanced heart and lung disease. Canadian eligibility criteria may broaden in the coming years to include lower BMI patients considering the revised guidelines from the American Society for Metabolic and Bariatric Surgery released in October 2022, especially for those with type 2 diabetes.1,2 Although traditionally, it was believed that metabolic surgeries induced weight loss by creating restrictions to food intake and malabsorption, current research demonstrates that the drivers for weight loss are the profound physiological and metabolic changes that alter energy balance occurring after bariatric surgeries (ex. decrease in ghrelin, increase in GLP-1 agonists, decrease leptin, changes in gut microbiota) in addition to the different degrees of food intake restriction and/or malabsorption of nutrients.
Once eligibility has been established, patients are evaluated for their fitness to endure weight loss surgery and the post-operative course. A comprehensive medical, dietary and psychosocial evaluation is done by a multidisciplinary team composed of a registered dietitian, a psychologist--psychiatrist or a social worker, a surgeon, and specialty nurses. A registered dietitian will assess the patient’s eating habits and nutritional status and educate patients on the changes required to succeed for surgery. A social worker and/or psychologist will explore the patient’s motivation and readiness for surgery, reinforce realistic expectations post-operatively, evaluate their psychological well-being and screen for eating disorders to ensure patients are optimized psychologically to achieve the best possible outcomes. If psychiatric concerns are identified in the pre-operative screening, treating these conditions is usually best practice before proceeding with surgery. Extensive blood work is done to screen for nutritional deficiencies and associated comorbid metabolic conditions, including diabetes, dyslipidemia, and fatty liver disease. The bariatric surgeon will frequently request an upper endoscopy and a liver ultrasound before surgery. For high risk patients, consultations with a specialist (internal medicine, cardiology, respirology, etc) can be considered. Additional complementary tests can include but are not limited to polysomnography, echocardiogram, and cardiac stress testing on a case-by-case basis.
The most common bariatric procedures offered across Canada are vertical sleeve gastrectomy (VSG) and RYGB -(Figure 3). Unfortunately, inter-provincial resource variability can impact access to regional bariatric surgery centers of excellence. Less than 5% of bariatric centers across Canada also offer a Double Anastomosis Duodenal Switch (DS/DADS) or Single Anastomosis Duodenal Switch (SADS/SADI) procedure likely due to lack of funding and surgical expertise. For the VSG, the surgeon removes 80% of the stomach, mainly the distal stomach where “ghrelin” the primary hunger hormone, is secreted. The new much smaller stomach accommodates less food therefore, the volume of food intake is reduced in addition to physiologically lower levels of hunger. In the RYGB, the surgeon creates a small gastric pouch anastomosed to the jejunum; therefore, the ingested food bypasses the remaining stomach and 150 cm of the proximal small bowel. The smaller stomach can only accommodate a smaller amount of food, and malabsorption of nutrients occurs by bypassing the proximal small bowel. The proximal small bowel is where the potent satiety hormone GLP1 is secreted. This makes patients feel physiologically fuller while benefiting from a smaller volume allowance in their gastric pouch. This is also why metabolic improvements are noticed immediately post-operatively as GLP1 can have a profound impact on increasing insulin sensitivity. The duodenal switch with or without biliopancreatic diversion is a highly malabsorptive procedure and is limited to patients with BMI over 55 kg/m2 with associated comorbid conditions. Matching the most appropriate bariatric procedure to a patient and their needs is an integral part of a bariatric surgeon’s role within the multidisciplinary team. Regions across Canada that offer the full spectrum of bariatric procedures are best positioned to tailor a procedure to a patient’s needs.
Figure 3. Different types of bariatric surgeries, Bariatric Surgery: Surgical Options and Outcomes - Canadian Adult -Obesity Clinical Practice Guidelines. From left to right: Adjustable gastric banding, Roux-en-Y gastric bypass, sleeve -gastrectomy and biliopancreatic diversion with duodenal switch. Copyright: Graphic department, Quebec Heart and Lung Institute, Laval University. Reprinted with permission.
On average, patients can expect to lose 50–75% excess weight loss (EWL) after a sleeve gastrectomy and gastric bypass surgery. Half to three-quarters of those patients maintain this EWL at 10 years. Surgical weight loss among VSG and RYGB patients is associated with significant improvement and/or a resolution of adiposity-related comorbidities, including diabetes, dyslipidemia, OSA, and HTN (reductions by 60–80%, 60–65%, 45–50% and 60–80% respectively). All-cause mortality is also reduced after surgery, most notably due to lower death rates associated with CAD, DM2, and cancers (reductions by 59%, 92%, and 60%, respectively).
Patients are often surprised to learn that bariatric surgery is typically performed laparoscopically and offers lower rates of complication, readmission, and mortality rate than laparoscopic gallbladder and appendix surgery (ACS-NSQIP reported RYGB 30-day post-operative complications 3.4%, readmission 6.7%, mortality 0.3%). Complication rates for bariatric surgery reported in large database studies fall between 2–4% and include early complications, such as bleeding and anastomotic leak, and late complications, such as GERD, ulcers, internal hernia, and nutritional deficiencies.
Table 3 outlines the procedures mentioned above, their mechanism of action, and key considerations applied when evaluating their suitability for a patient. Revisional or conversion procedures are offered at all bariatric centers, defined as correcting a complication or modifying a previous bariatric surgery due to lack of effectiveness. No publicly funded hospitals currently offer laparoscopic adjustable gastric bands, single anastomosis gastric bypass (OAGB), or the now historic vertical banded gastroplasty due to the lack of long-term efficacy seen with procedures and increased rates of complications. These surgeries have also not been endorsed by the clinical practice guidelines. For the most part, endoscopic approaches to weight loss have not gained favor in Canada yet, albeit a handful of centers may offer a temporary intragastric balloon for short-term weight loss bridging to a definitive procedure.
Table 3. Most common bariatric procedures performed in Canada, Mechanism of action, Key features & Patient considerations
| Procedure | VSG | RYGB | DS/SADI |
|---|---|---|---|
| Mechanism of Action | Restrictive + Hormonal | Restrictive + Hormonal + Malabsorptive | Restrictive + Hormonal + Malabsorptive |
| Key Features | •50–60% 10yr EWL •~45 min procedure •Technically easier in High BMI patients |
•50–60% 10yr EWL •Anti-reflux procedure •Technically challenging, sometimes prohibitive in High BMI patients and those with previous abdominal surgery |
•60–70% 10yr EWL •Best rate of obesity comorbidity remission •1 or 2 stage procedure •Technically challenging, sometimes prohibitive in High BMI patients and those with previous abdominal surgery |
| Notable Considerations |
•NSAID safe •No malabsorptive component to impact oral medication profile •Irreversible, but can be revised, converted •Re-operation rate 2.97% •Increases GERD in ~20% of patients •Staple line leaks can be more challenging to manage compared to RYGB |
•NSAID unsafe (Marginal ulcers) •Malabsorptive component can affect oral medication absorption •Reversible •Re-operation rate 0.7–7.5% •Anastomotic strictures •Internal hernias •Marginal ulcers (NSAID unsafe) •Dumping syndrome •Biliary complications can be challenging to manage |
•NSAID safe (pylorus preserved) •Good 2nd stage procedure for weight recidivism •Malabsorptive component can impact oral medications and put patients at high risk for macro- & micronutrient deficiencies •Reversing can be difficult •Internal hernias •Biliary complications can be challenging to manage |
*Lists represented here are not comprehensive nor intend to be, statistics may vary between sources.
Back to the case! Your assessment: Anne has Class III, EOSS 3 obesity.
She meets the criteria for consideration of bariatric surgery and appears motivated to proceed. She has already made lifestyle changes to improve her health. In addition, she is on medications (metformin, empagliflozin, and semaglutide) that are not only used to treat her diabetes but also promote weight loss and optimize her diabetes renal disease. However, after reviewing her other medications, you discuss with Anne to consider switching from citalopram to a more weight-neutral agent.
Obesity as a chronic, complex disease is reviewed with Anne with an emphasis on reducing her internalized weight bias through understanding that her physiology is resisting her attempts to lose weight and that it is not a result of a lack of willpower. She is asked if she would consider metabolic surgery her next best option. Anne asks why she was not offered surgery before; she is explained that a common barrier to referral for metabolic surgery is the physician’s lack of understanding of the surgery and its outcomes, especially on metabolic health. In addition, there is still significant bias and stigma within the healthcare system that leads to long wait times and a lack of discussion about obesity treatment. She is also informed that she fits within the typical patient who would benefit from surgery given her class III obesity and poorly controlled diabetes. She is reassured that the benefits of bariatric surgery likely outweigh the risks, especially for a patient like her.
She is offered a referral to a bariatric center of excellence in her province where she will be assessed by a multidisciplinary team. As part of her journey, she will be given educational tools and will have to attend nutritional sessions and pre-surgery classes. She knows that the average wait time from referral to surgery is 1–2 years depending on the surgical center. Anne also explained that the results of metabolic surgeries are variable and not guaranteed but that the average weight loss with surgeries is 30–40% of total body weight. Most importantly, as per her pre--specific goals, her metabolic health and mobility are likely to improve while needing less medications, and, most importantly she will have an improved quality of life. When Anne meets her surgeon, she will discuss potential short- and long-term complications of surgery and the best type of surgery for her. Given her type 2 diabetes history and current weight, she will likely achieve higher rates of diabetes remission with the RYGB. Anne leaves satisfied with all information given and looks forward to her referral to the bariatric clinic.
Biertho L, Hong D, Gagner M. Canadian Adult Obesity Clinical Practice Guidelines: Bariatric Surgery: Surgical Options and Outcomes. Available from: https://obesitycanada.ca/guidelines/surgeryoptions. (Accessed 15 November 2022).
Eisenberg D, Shikora SA, Aarts E, et al. 2022 American Society for Metabolic and Bariatric Surgery (ASMBS) and International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO): Indications for Metabolic and Bariatric Surgery. Surge Obesity Relat Dis 18 (2022) 1345–1356. Available at: https://www.soard.org/article/S1550-7289(22)00641-4/fulltext
(Objective: Discuss the Neurohormonal and Adaptive Mechanisms that Predispose Patients to Weight Regain, Discuss Modulators to Assess (Ex. Sleep Apnea, Medications Etc., Discuss Rate of Weight Regain after Different Treatments (Lifestyle Changes vs. Medications vs. Surgery)
John is a 55-year-old factory worker who has been struggling with his weight for most of his life. He underwent RYGB surgery 6 years ago and was initially successful at reducing his weight by 25% of his total body weight (pre-operative BMI: 43, lowest post-operative BMI: 32). He felt great, was active on most days, and was eating well.
Over the last 2 years, he mentions that his weight has increased. He recently lost his father and has been struggling with low mood. He was started on an antidepressant and has gained 35 pounds since then. His current BMI is 37. During the last 2 years, he has tried multiple different dietary plans to help combat his weight, including seeing a registered dietitian. He mentions that he is feeling hungrier than before and thinks about food all the time now. He can’t enjoy going to a restaurant with his wife due to his fear of further weight regain. He also feels that his mood would be better if his weight was better controlled, and he can’t stand to look at himself in the mirror because he feels like a failure.
His past medical history includes a reoccurrence of sleep apnea. He is taking paroxetine for his depression. His metabolic labs reveal mildly elevated liver enzymes, and an ultrasound consistently with moderate fatty liver disease, he has mild fatty liver before his bariatric surgery, but this was resolved post-operatively.
John is notably frustrated today at his appointment and approaches you with the following questions:
Why does weight regain happen?
What are some things my doctor should consider when I am regaining weight?
What are additional available treatments?
Weight regain is a common problem despite adequate treatment for obesity. The etiology of weight regain is likely multifactorial given that obesity is a complex, progressive chronic medical condition related to an interplay between our biology, environment, genetics, and hormones. Although we still do not have adequate evidence to predict who will be successful long-term and who will regain weight, some data support closely monitoring those who may be at higher risk.
Despite bariatric surgery being the most effective long-term treatment for obesity, there are still clinical challenges with weight regain. Approximately 80% of surgical candidates post-bariatric surgery will experience a weight loss of at least 20% of their pre-operative body weight and an average of 60 to 75% of excess body weight within 18 to 24 months. A non-response to bariatric surgery either immediately after bariatric surgery can be defined as less than 10% weight loss at six months or delayed weight loss of less than 20% at one year and may occur in up to 20% of individuals. However, due to obesity as a chronic disease, weight regain can still occur in up to 30% of bariatric surgery patients and remains clinically challenging for patients and healthcare providers.
There is no standardized measure for weight regain. This results in difficulty interpreting the data of the true incidence of weight regain especially after bariatric surgery. However, utilizing the percentage of maximum weight loss as a measure of weight regain is strongly associated with the recurrence or worsening of hypertension and diabetes, as well as a physical and mental decline in quality of life. Therefore, weight regain is commonly defined as a weight gain greater than 25% of the maximum weight loss and does not consider the patient’s health status or the time elapsed since surgery.
Although again, in most cases, weight regain is likely multifactorial, predictors of weight regain after bariatric surgery can include a baseline BMI greater than 50 and psychiatric comorbidities. In addition, post-operatively, lack of self--monitoring, continuing to eat past fullness, grazing, a higher binge eating scale score at 12 months, and a loss of control of eating after surgery have also been predictors of weight regain. This highlights the need for patient support with behavior change and psychological intervention pre--operatively through a multidisciplinary team in a bariatric centre of excellence to optimize the success of bariatric surgery patients. In addition, access to care for patients who experience weight regain after bariatric surgery with a complete assessment of the etiology and understanding of treatment options is imperative to prevent recurrent comorbidities.
Regardless of the treatment type, each patient should have a comprehensive obesity assessment when seeking help for weight regain. A similar approach to an initial evaluation of obesity is likely sufficient to address concerns about weight regain, with a specific emphasis on causes and complications associated with weight. We recommend starting the conversation by asking permission, reviewing obesity as a chronic disease, and addressing internalized weight bias. Reviewing modulators that can affect weight regain is likely the next best step. Modulators can include increased stress, emotional eating, change in environment, new or worsened psychiatric illness, sleep disturbance or untreated sleep apnea, eating disorders, or new weight--promoting medications. A complete history of these modulators helps understand the root cause of weight regain.
The most likely cause of weight regain is still likely our innate biology. Given that our body defends weight loss through neurohormonal and metabolic adaptation, resulting in an increased appetite and slowing down of our metabolic rate, most interventions that rely solely on calorie restriction and increased activity alone will likely result in weight regain for most people. This biological predisposition is treated using 1 or more of the 3 pillars of obesity, psychological intervention, pharmacotherapy, and bariatric surgery. These same pillars should be considered in those with weight regain.
Weight regain can also often be caused by a change in nutrition. This can be due to multiple reasons, including increased physiological appetite, a reduced calorie intake that was unsustainable, or too restrictive or modulators (as above). The highest weight maintenance likelihood is linked to a sustainable nutrition plan. Post bariatric surgery, some additional nutritional risk factors likely should be reassessed by a registered dietitian at a bariatric center of excellence.
Post bariatric surgery re-evaluation could include but is not limited to:
Lack of adherence to the post-operative dietary program
Lack of support
Noncompliance with post-operative appointments
Self-reporting inaccuracy resulting in underestimation of oral intake
Sub-optimal protein intake
Intolerance of food choices
Vitamin and mineral deficiencies
Increased hunger
Rewards influence such as cravings (ex., mood disorders, other modulators)
New or old eating behaviours which may be maladaptive
Substance abuse
Nutrition strategies to combat weight regain could include but are not limited to:
Food journaling
Establishing a meal routine
Understanding the impact of grazing
Separating liquids and solids during the meal
Minimizing liquid calories
Unrecognized or untreated eating disorders and lack of control of eating/appetite regulation pose a high risk for weight regain and failure to lose weight with obesity treatment. Many psychiatric medications are also weight-promoting which adds an additional challenge to seeking and adhering to treatment. Depression and/or lack of regulation of the effect and disturbances with body image may also result in sub-optimal weight loss or regain and does not necessarily improve with weight. Negative or self-critical thoughts are a common reason for lack of motivation and likely both a cause and consequence of weight regain. Psychological interventions, including cognitive or acceptance-based behavioural therapy, addressing untreated mood psychiatric conditions, weight acceptance, peer and community support groups, and stress management therapy may also be helpful in the treatment of weight regain.
The use of pharmacotherapy for the treatment of obesity is safe and effective for the treatment weight regain. The same criteria, including a BMI >30 kg/m2 or a BMI >27kg/m2 and adiposity-related complications, is recommended to start pharmacotherapy for weight regain; however, the considerations may differ after bariatric surgery. For example, there is likely reasonable evidence to show that preventing further weight regain or worsening metabolic disease in a patient who does not meet the BMI criteria is a reasonable consideration after bariatric surgery. It is also well understood that treating early and at a lower weight will likely improve outcomes better than waiting until the majority of weight has been regained to start pharmacotherapy. All approved Health Canada options can be considered in this clinical setting, depending on the patient’s individual needs (see Question 1 for details). Although the obesity clinical practice guidelines recommend reassessing the effectiveness of pharmacotherapy agents after 3–6 months, if weight regain is seen on pharmacotherapy, the above assessment is critical to understanding the cause and then considering changing to a different pharmacotherapy agent or considering add-on therapy would be recommended.
Surgical etiologies accounting for non-response to bariatric surgery and weight regain are rare but must be considered. These include a gastro-gastric fistula, remnant fundus, or pouch or sleeve enlargement. Radiographic investigation, including an upper gastrointestinal series or endoscopy, may be necessary to rule out these abnormalities. Conversion surgery may be an option for ongoing weight loss in those individuals where other factors such as anatomical, nutritional, medical and psychological factors have been considered. These surgical procedures include revision of the VSG to either a duodenal switch or RYGB or revision of the RYGB to a duodenal switch. This is, of course, based on the recommendations of an assessment from a multidisciplinary team at a bariatric center of excellence to determine the best candidate for these procedures.
Assessment: John is a 55-year-old gentleman with class II, EOSS 1 obesity, with weight regain post bariatric surgery.
You review with John that obesity is a chronic medical condition and how his biology is set up to defend his highest weight, making his current strategies to reduce and maintain weight ineffective in the long term. You also discuss that increased hunger and reward/pleasure-seeking from food with calorie restriction is one way the body promotes weight regain. He feels better with this explanation and is empowered that his lack of success is not due to a lack of effort.
Upon review of modulators of weight, he is agreeable to starting treatment for his untreated sleep apnea as this may play a role in his lack of appetite regulation and his metabolic health. He is also agreeable to discussing changing his antidepressant to one that is less weight promoting like bupropion.
He would like to consider starting a food diary to understand better his high-risk times of day where he feels hungrier and has cravings and is planning to work towards a dietary plan that is sustainable and that he can enjoy long term.
Given his BMI and metabolic health, pharmacotherapy is reviewed and discussed in detail. He would like to consider either a GLP1 RA or naltrexone/bupropion, given his depression. He would like to read the materials you gave him and discuss them on his next visit. He may consider revision surgery for his weight; however, he prefers to consider medical treatment before initiating this discussion.