We'll be talking today about anti-obesity medication and its use on weight regain post-bariatric surgery. The objectives of this presentation is to outline the role of anti-obesity medications in treatment of post-bariatric surgery, weight regain, and promotion of weight maintenance. Also to outline the comprehensive pre-operative and post-operative considerations for weight loss surgery to ensure patient safety and well-being. Bariatric surgery has been increasing exponentially throughout the years, with 2019 reaching almost 60% of them being sleeve surgery followed by Roux-en-Y gastric bypass surgery after. There are different types of gastric bypass surgery and procedures. On the left, you'll see the four most common surgical procedures used, including the Roux-en-Y gastric bypass, gastric bending, sleeve gastrectomy, and biliopancreatic diversion with duodenal switch. On the right, you can see the procedures used, including the reshape balloon, ellipse balloon, spats balloon, ob-balloon, and orbura balloon. And on the bottom, including some other procedures used as well, with the latest addition being the GELASYS 100, which is a capsule taken by mouthful, but it's considered to be one of the procedures. Assessing the patient pre-operatively is very important. It's important to assess the nutritional status, the psychological status, as well as the medical status of the patient for the risk assessment, including cardiovascular, thromboembolic risk, and even sleep apnea risk. The patient should have a variety of labs being done, identify potential vitamin deficiencies, and adjust the medications pre-operatively. It's important to understand the gastrointestinal sites of absorption of vitamins and minerals in this population, especially as types of surgeries can vary, as well as the procedures, to better assess vitamin deficiencies. In the stomach, the intrinsic factor will bind to the vitamin B12. The duodenum will start absorption of some of those minerals and vitamins, including all the fat-soluble vitamins, the folate, the iron, the magnesium, the phosphorus, and the calcium, and as well some protein absorption. In the jejunum, you will continue to have absorption of the fat-soluble vitamins, as well as the folate, zinc, magnesium, manganese, phosphorus, calcium, and iron. The B12 will be then absorbed, as well as water. In the ileum, you continue some absorption of vitamin B12, and on the large intestines of your sodium chloride, potassium, and vitamin K. In 2019, ACE, along other societies, released a clinical practice guideline outlining and recommending pre-operative and perioperative management for patients undergoing bariatric surgery and other procedures. On the pre-operative evaluation, it's important to have a completely HNP of these patients, including obesity-related comorbidities, the cause of obesity, weight, BMI, weight loss history, commitment, and any risks related to surgery. On the routine labs, those important labs include a fasting blood glucose and lipid panel, kidney function, liver profile, lipid profile, a urine analysis, coagulation factors, blood type, and CBC. Nutrient screening pre-operatively is very important, with iron studies, B12, folic acid, as well as vitamin D status. And you might consider additional testing for those undergoing malabsorptive procedures based on symptoms and risks as well. Cardiopulmonary evaluation with sleep apnea screening is extremely important pre-operatively, and including your EKG, your echocardiogram, if indicated, if any history of cardiac disease or pulmonary hypertension, and as well as any evaluation for a risk for deep venous thrombosis. On the GI evaluation, it's important to assess for the H. pylori screening, especially in areas of high prevalence, gallbladder evaluation, and a nail perendoscopy. On the endocrine evaluation, it's important to assess an H1A or A1C for those patients that are with suspected or already diagnosed prediabetes or diabetes, a TSA for patients that have symptoms or an increased risk for thyroid disease, androgens for those with a history of PCOS, and a screening for Cushion Syndrome, if clinically indicated. Cardiomedication evaluation with healthy eating index, cardiovascular fitting, strength training, sleep hygiene, mood and happiness, alcohol use, substance abuse, and commitment engagement is extremely important, and that should be done in conjunction with your exercise physiologist, nutrition as well, behavioral and food therapist. Medical nutrition evaluation by a registered dietitian, psychological behavioral evaluation, assess for individual psychological support, counseling if needed, and document any medical necessity for the bariatric surgery. It's important to have an informed consent, and the patient should be aware of relevant financial information, and the continual efforts for preoperative weight loss, optimize glycemic control preoperatively can render benefits, including postoperatively. Pregnancy counseling for those patients that they should be counseled to avoid pregnancy for the next 12 months. Smoke cessation is extremely important, and patients should stop smoking preoperatively, and assess cancer screening by providers, including primary care physicians. The main nutrient deficiencies after bariatric surgery, including the vitamin B1, the thiamine, B12, iron, folate, D and calcium, vitamin A, E, K, zinc, and copper. Vitamin B1 occurs anywhere from 1 to almost 50% depending on the procedure, and post weight loss surgery time frame. The screening for those with high risk is very important, and those including females, African-Americans, patients not attending a nutritional clinic after surgery, patients with GI symptoms, including intractable nausea and vomiting, jejunal dilation, megacolon or constipation, patients with conditions such as cardiac failure, especially those receiving furosemide, patients with a small bowel bacterial overgrowth, malnutrition, excessive or rapid weight loss, and excessive alcohol use. And patients that have undergone weight loss surgery with symptoms or risk factors should be assessed for vitamin deficiencies at least during the first six months, and then every three to six months until symptoms resolve. To avoid vitamin B1 deficiency, as a supplement, patients should be receiving 12 milligrams of thiamine daily, preferably in a dose of 50 to 100 of thiamine from a B-complex supplement of high potency multivitamin. The refeed will vary based on your oral, IV, IM, and they should be added as well, magnesium, potassium, and phosphorus to avoid the risk for refeeding syndrome. Vitamin B12 is another very common vitamin deficiency post weight loss surgery, usually occurs two to five years post surgery, and the risks will vary based on the surgery, with flu and Y-gaseous bypass being around 20%, and this leave anywhere from 4% to 20%. Vitamin B12 supplementation is recommended for all patients undergoing any bariatric surgery. They screening more often every three months in the first year post surgery, and then annually. And more often screening for those taking nitrous oxide, neomycin, metformin, colchicine, any proton pump inhibitors, and seizure medications that can increase risk of vitamin B12 deficiency. Serum MMA, with or without homocysteine on those with history of B12 or pre-existing neuropathy should be checked, and usually occurs, the vitamin can occur due to the food intolerance or the restricted intake of protein, and vitamin B12 containing foods. The supplement should be a disintegrating tablet, sublingual, or liquid for better absorption, or the nasal spray option. The parietal is also can be used, either an IM or subcutaneous option, and the refeed can be on higher doses of 1,000 milligrams daily until normal levels have been achieved, and then maintenance after. Iron deficiency can occur in up to three months, as well as after 10 years post weight loss surgery, and it's going to vary significantly based on the type of bariatric surgery done. Deficiency can still occur despite supplementation, so that's why it's important to screen every three months after surgery, and then every three to six months to 12 months after, and if no deficiency, annually thereafter. It's important to include not only the iron, but the iron panel, the CBC, your transferrin iron binding, and as well ferritin and transferrin receptor, if available on your labs. It's screened more often based on any clinical signs or symptoms or suspicion. The supplementation will vary in males and patients without a history of anemia is 18 milligrams, usually from multivitamins. Women that are still menstruating and that underwent any bariatric surgery that can cause deficiencies on vitamins and irons should receive 45 to 60 milligrams of elemental iron daily from all vitamins and mineral supplements. Vitamin C should be taken apart from calcium, acid-reducing medications, and foods high on phthalates or polyphenols. Adding vitamin C will increase the absorption and decrease the iron overload. For the refeed phase, it can either be oral as the best option, as IV is not responsive, usually does not respond well, as well as the oral therapy. Malignant acid can occur, the deficiency in up to 65% of patients, so it's important to screen all patients, especially women of fertile age, those with poor diet of folate as well, and if you suspect the patient has not been adherent to multivitamins. Supplemental phase will be 400 to 800 daily multivitamins, higher doses in women of childbearing age. The refeeding phase, it's 1,000 milligrams daily, then you resume maintenance dose after. And doses that are much higher than that are not recommended due to the risk of masking a vitamin B12 deficiency. Vitamin D and calcium deficiency, with vitamin D deficiency occurring in almost 100% of all patients, so it's important to screen all of those patients. Check vitamin D, hydroxy D. Check additional labs such as PTH or bone formation of resorption markers can be considered based on the clinical practice as well as any suspicion of signs or symptoms. The supplementation will vary, so if this is a biliopancreatic diversion or duodenal switch, with duodenal switch, it's 1,800 to 2,400 milligrams daily. The other bariatric surgeries are 1,200 to 1,500 milligrams daily. In order to increase absorption, it's important to divide the doses. Remind that calcium carbonate should be taken with meals, while calcium citrate may be taken with or without meals, but might require higher doses based on what's availability on the supplementation. The vitamin D is usually recommended 3,000 daily, but will vary drastically based on the serum levels. The goal is to keep the vitamin D levels above 30. The refeed phase is usually recommended anywhere from 3,000 to 6,000 daily or 50,000 of the vitamin D2 once or twice weekly. It's going to vary drastically based on the levels and as well as the absorption. Vitamin D3 is recommended over vitamin D2. This is a more potent treatment when comparing frequency and amount needed for repletion as well as better absorption. Vitamin A deficiency can occur in up to 70% of patients within four years of surgery. So it's important to screen the first post-operative year especially those that are undergoing biliopancreatic diversion with duodenal switch independent of any symptoms and especially attention for those with evidence of protein calorie malnutrition. The supplementation will vary based on the type of the surgery, the gastric bending being 5,000, the rho and y as well as leave 5,000 to 10,000 daily and the duodenal switch up to 10,000 units daily. The refeed is going to vary based if there are any changes or not. It's important to also evaluate for iron and or copper deficiency as those can impair any resolution of vitamin A deficiency. Vitamin E deficiency is not common. It's only screening on those that present with any symptoms and the supplementation is around 15 milligrams daily. The refeed dose has not been defined. The vitamin K is another one deficiency that's not common and again to only screen with those with symptoms. The doses again will vary based on the type of surgery but special attention and those being carried is those that are women that are pregnant. Zinc deficiency increase based on the type of surgery with biliopancreatic diversion carrying the risk of around 70 percent. The deficiency can still occur despite any supplementation. Thus it's important to screen annually using serum and plasma zinc. All patients undergoing weight loss surgery should take at least four times of the recommended daily allowance dose of zinc and reminder to do a ratio for 1 to 15 of zinc to 1 of copper to minimize the risk of copper deficiency. The refeeding it's not being defined but careful to not overdo it and induce copper deficiency. Copper deficiency can occur in 90 percent of those undergoing the duodenal switch. So again it's important to screen annually despite of symptoms or clinical signs using serum copper and seroplasmin and as similar to the copper other patients should be taking a higher dose but reminder to keep a ratio. It's best to use copper gluconate or sulfate as recommended source for copper for the refeed as well as supplementation and the supplementation at the refeed is going to be based on the severity of the symptoms with a higher dose for those with severe. It's important to monitor levels every three months until back to normal. In summarizing the post-operative recommendations are that multivitamins containing iron folate and thiamine should be taken daily. Calcium citrate is a better option due to not depending on meal intake between 1200 to 1500 milligrams in divided doses. The vitamin D3 of 3000 units daily. Vitamin B12 preferably on the sublingual or subcutaneous or IM form as well as your iron. Based if any risks if additional is recommended. No NSAIDs and tobacco use are recommended post-operative. It's important to avoid pregnancy for the next 12 to 18 months. Minimize alcohol intake to pretty much no alcohol intake on those patients and we should be screening for vitamin deficiencies every 3 to 6 to 12 months. More often if clinical symptoms or signs or any suspicion of deficiency as well if you are doing the refeeding phase for some of those deficiencies and that would include your calcium, your vitamin D hydroxy D, your vitamin B12, B1, folate, iron studies, some fat soluble vitamins as indicated and your zinc as well as copper. Monitor weight loss response it's extremely important and as well as the psychological monitoring which is going to be long term. Patients undergoing weight loss surgery should continue any behavioral support pre-surgery. If they are already taking psychotropic medications they are to be continued based on the behavioral therapist or any provider that has been prescribing them. They need to be monitored for any severe mood changes or eating disorder symptoms or psychological changes and they should continue have follow-up with the bariatric psychologist after surgery. As I mentioned before it doesn't stop with surgery it's a continued monitoring and it's usually 1, 3, 6 and 12 months and annually thereafter but it can be more frequent if needed based on the recommendations by the bariatric psychologist. In shifting gears and talking about the way to regain post-surgery the definition it's still not very clear but most seem to agree that this can be defined as suboptimal which means less than 50% of the estimated weight loss versus failure which is more than 50% of the nadir weight. With that keep in mind that 30 to 87% of those undergoing weight loss surgery will regain the weight and usually it's around a median of a mean of 25.2% that will regain max weight at the year 5. The question is when should we intervene on those situations? As seen on this slide the definition can vary based on what are we using as a terminology. So using a expected weight loss it's around 25% weight loss from nadir up some people defined as 50. Using a nadir weight, using a nadir weight based on kilograms, using maximum weight loss, using pre-surgery weight, using weight regain after remission, using any way to regain or using BMI. There are some other definitions for insufficient weight loss and that would be more defined as using expected weight loss, weight regain and ideal weight loss and that's going to be varied based on the type of surgery or procedure that was done. As clinicians we should be assessing for potential causes for the weight regain. That's going to be varied based if we're talking about hormonal or metabolic causes, if we're talking about dietary non-adherence, physical inactivity, mental health is extremely important both operatively to be addressed and if any anatomical surgical failure depending on the type of surgery or procedure done. The predictors for the weight regain including your older age, male gender, a higher pre-operative BMI, mental health issues and presence of any comorbidities such as diabetes type 2, hypertension and sleep apnea. The prevention and management of some of the causes that are behavior related should always include a cognitive behavioral therapy, a remote acceptance based behavior intervention or lifestyle counseling. So there are different options for continual behavior therapy for those patients as outlined above. With weight regain being so multifactorial addressing if there would potentially be an anatomical cause, so the surgeon should be addressing if there is any surgical failure including pout dilation, enlarged anastomosis, band complications, fistula or stoma dilation. Psychological, it's going to be based on weight promoting medications, so any clinicians should be looking for this potential new medications that have been added to the regimen that potentially can cause weight gain. Pregnancy that occurred recently, menopause status, if there is indeed a smoking cessation, endocrine disorders such as cushions, if clinically indicated, microbiome changes, gut peptide changes, the bio acid due to absorption and then an immune functioning status. On the behavior side, addressing dietary changes, if patient is back to old habits, are we consuming high density foods, if any binge eating disorders prior to surgery are, if they are reoccurring now, there's been a decrease, if there's been a decrease in physical activity and if those with a history of depression and anxiety, if there has been an increase on those symptoms, if the patient has now consuming more alcohol, back to smoking, non-adherence to any of the treatment of lifestyle changes, dietary and exercise, but as well important to address the lack of follow-up due to stress, work-related or most recently due to COVID pandemic. Addressing loss of support and that including the social support and family support for those patients. So what can we do to help those patients? So continue follow-up with the bariatric team, with the behavioral side, with the dietary, it's extremely important to address potential non-adherence treatment or increase of any psychiatric psychological condition that imposing now the way to regain for those patients. On the pharmacological side, there are some FDA approved medications that have been used for weight loss that have been now tried and used successfully for weight regain, post-periodic surgery. There's also some other options off-label as outlined on this slide. On the surgical management, there are options for conversion depending on the type of surgery that was done, a conversion for a different type of bariatric surgery. Pharmacological use of medications for post-bariatric surgery with weight regain has been used for those with suboptimal response to bariatric surgery. However, there's still limited data. The use of fentamine with topiramate alongside sleeve gastrectomy increases and more potentiates the weight loss response on those patients undergoing this type of surgery compared to those that undergo only surgery. The use of incretins have been tried on those patients The use of incretins have been tried on those patients undergoing post-bariatric surgery with weight regain. In this case, the GLP-1 receptor agonist and it seems to carry a more effective weight loss response post-weight regain bariatric surgery in up to 6.9% of weight loss 9 months post-surgery. In this slide, as you can see, the use of a GLP-1 receptor agonist in weight reduction for those patients that have not achieved a successful weight loss response post-bariatric surgery. They have been tried on either litoglutidin or semaglutidin for 6 months and semaglutidin seems to carry a much more weight loss response than even compared to litoglutidin. I'm showing more clearly on this slide. Litoglutidin carried a weight loss of around 8.8% post-bariatric surgery when used for 6 months, while semaglutidin led to almost 13% of weight loss post-bariatric surgery on those that failed. Seen on this last slide, the weight loss response up to 5% in most of the patients, but as up of 20% as well in some categories of those patients with a better response to semaglutidin.

anti-obesity medication

weight regain

bariatric surgery

nutrient deficiencies

supplementation

weight loss maintenance

nutrient screening

psychological well-being

GLP-1 receptor agonists