4 5 6 Weight Management Programs.docx

Weight Management Programs Learning Objectives Recognize determinants of weight gain including genetic, environmental, biologic, and behavioral factors Explain the pathophysiology and pharmacokinetics of obesity Identify medications or disease states that may increase the risk of weight gain Classi...

Weight Management Programs Learning Objectives Recognize determinants of weight gain including genetic, environmental, biologic, and behavioral factors Explain the pathophysiology and pharmacokinetics of obesity Identify medications or disease states that may increase the risk of weight gain Classify a patient’s obesity based on body mass index (BMI) or weight circumference Compare and contrast popular diet programs Describe the following for FDA-approved medications for weight loss: indications, contraindications, duration of use, adverse events, and unique counseling points Counsel a patient on the safety and efficacy of bariatric surgery Using the 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults, recommend a plan for the treatment of obesity based on a patient’s BMI and comorbidities Background Defining Overweight & Obesity Adult Obesity in the U.S. Adult obesity in the US: 41.9% Up from 30.5% in 2000 Expected to hit 50% by 2030 Additional annual cost: $1,861/year Healthcare cost Productivity lost Transportation needs Disproportionately affects certain populations: Black (49.9%) > Hispanic (45.6%) > White (41.4%) > Asian (16.1%) 40-59 years old (44.3%) > 60+ years (41.5%) > 20-39 years old (39.8%) Impacted by Social Determinants of Health: Less education > college degree Middle income > low income = high income Pathophysiology Determinants of Weight Gain Nutrition Inadequate food supply Binge eating Diet high in carbohydrates Sedentary lifestyle Chronic Disease PCOS Hypothyroidism Dyslipidemia Organ failure Type 2 Diabetes Schizophrenia Depression Injury Foot fractures Joint dislocations Back injury Energy Balance Energy balance = intake + storage – output Appetite Regulation Common Appetite Stimulators: Ghrelin (in the gut) Norepinephrine Serotonin Common Appetite Suppressors: Leptin (in the fat tissue) GLP1 (in the gut) GIP (in the gut) Pharmacokinetics of Obesity Absorption Changes in obesity: ↑ visceral blood flow ↑ gut permeability ↑ gastric emptying time Outcome: Conflicting evidence, but absorption likely similar to normal BMI Distribution Changes in obesity: ↑ adipose tissue ↑ blood volume ↑ cardiac output Δ to plasma proteins Outcome: Highly variable depending on drug lipophilicity, perfusion, permeability molecular weight, protein binding, and ionization Some drugs have specific Vd equations: Theophylline Vd(L) = 1.29 x TBW0.74 Aminoglycoside Vd(L) = (0.26 L/kg) x AdjBW Ask your preceptor: most institutions have their own weight-based dosing protocols specific to that practice site *AdjBW is used when drug distributes into both lean and adipose tissue Metabolism Excretion Changes in obesity: Δ to glomerular filtration Δ to creatinine clearance Δ to tubular reabsorption ↑ drug half life (t1/2) Outcome: Highly variable, difficult to predict If volume increases due to obesity, the elimination constant decreases... $\downarrow Kel = \ \frac{\text{Cl}}{\uparrow V}$ If the elimination constant decreases, the drug half-life increases… $\uparrow t_{\frac{1}{2}} = \frac{0.693}{\downarrow Kel}$ Complications Complications of Obesity Metabolic syndrome leads to additional annual cost: $2,200/year For every 1 kg increase of weight, risk of osteoarthritis increases 13% Obesity linked to discrimination towards employment, college admissions, romantic relationships, and job earnings Benefits of Weight Loss Type 2 Diabetes Mellitus 5 to 10% weight loss lowers A1c 0.6 to 1% Meal planning intervention lowers A1c 1 to 2% If weight regain occurs, A1c remains lower than before Hyperlipidemia 3 kg (6.6 lbs) weight loss lowers triglycerides 15 mg/dL 5 to 8 kg (11 to 17.6 lbs) weight loss lowers LDL-c 5 mg/dL Hypertension 1 kg weight loss ≅ 1 mmHg reduction in BP (peaks at -5 mmHg) 5% weight loss reduces antihypertensives prescribed Other Benefits Reduces risk of all aforementioned complications Improves libido and erectile dysfunction Improves sleep quality and energy levels Improves mood and mental clarity Improves quality of life Guidelines Available Guidelines BMI Centric Treatment based on BMI Goal: lose a set amount of weight Examples: 2013 AHA/ACC/TOS NHLBI Complications Centric Treatment based on risk, presence, and severity of obesity-related complications Goal: treat or prevent complication Examples: 2016 AACE/ACE 2022 ASMBS 2013 ACC/AHA/TOS Guidelines Non-Pharmacologic Therapy Comprehensive Lifestyle Interventions Diet Modification Energy deficit required < 800 kcal/day not recommended Severely obese people will require more energy Physical Activity ≥ 150 min/week of moderate activity Start slow and gradually increase intensity Only modest weight loss as monotherapy Behavioral Modification Regular self- monitoring of food intake, physical activity, and weight Multiple sessions & group sessions are most effective Personal Disclaimer Diet culture can be dangerous by: Perpetuating eating disorders Disproportionately impacting women Leading to size-based oppression Healthcare providers should: Utilize reliable, objective, evidence-based resources that support weight loss Be cognizant of patients’ available resources and readiness for change Approach the conversation with careful concern and respect Connect patients to a registered dietitian, when possible Provide the same care, attention, and quality for all patients Diet Style: Very Low Calorie Very-low calorie ➔ <800 kcal/day Evidence: 2 RCTS saw greater weight regain ACC/AHA/TOS Recommendation 4e: Should be provided by trained practitioners in a medical care setting because of potential for complications Diet Style: Low Carb* Low Carb ➔ 20–30 grams carbs daily Evidence: Several RCTs support weight loss, but confounded by limiting calories ACC/AHA/TOS Statement 6a: Low-carb diet achieves similar weight loss compared to low-calorie or low-fat diets *Dangerous in patients with diabetes Diet Style: High Protein* High Protein ➔ 25–30% protein daily Evidence: 5 RCTs supporting weight loss, but confounded by limiting calories ACC/AHA/TOS Statement 5a: High- protein diet achieves similar weight loss to a typical protein diet (15%) when both are calorie restricted *Dangerous in patients with chronic kidney disease Diet Style: Pattern Changes* Intermittent Fasting No food for X hours (fasting), then intermittently eating meals during a set window of time Evidence: Mixed, not mentioned in clinical guidelines at all *Dangerous in patients with diabetes, pregnancy, history of eating disorder Diet Style: Low Fat Low fat ➔ <30% fat daily Evidence: Many RCTs supporting weight loss ACC/AHA/TOS Statement 4b: lower-fat, higher-carb diets have greater LDL-c reduction and lesser increases in HDL-c Diet Style: Low Calorie Low calorie ➔ 500 – 750 kcal/day energy deficit 1200 – 1500 kcal/day for women 1500 – 1800 kcal/day for men Evidence: Many RCTs supporting weight loss ACC/AHA/TOS Statement 10a: Use of liquid and bar meal replacements associated with increased weight loss at 6 months vs. balanced deficit diet Diet Style: Balanced Diet Mediterranean Diet, Vegan, or Vegetarian Evidence: 4 RCTs supporting weight loss, PLUS proven to reduce risk of major cardiovascular events DASH Diet Evidence: 2 RCTs supporting weight loss, PLUS proven to lower blood pressure Diet Modification Summary To achieve weight loss, energy deficit is required How energy deficit is achieved should be a patient-provider decision Generally, 1200-1500 kcal/day for women; 1500-1800 kcal/day for men 1 pound of body weight = 3,500 calories “Safe” weight loss is 1 to 2 pounds/week To lose 1 pound/week, subtract 500 calories/day from current intake Pharmacologic Therapy 2013 ACC/AHA/TOS Guidelines FDA Approved Agents Used in addition to lifestyle changes Use caution with drug-drug and drug-disease interactions Drugs for Short-Term Use (<12 weeks) FDA Banned Agents Many agents removed from the market due to safety concerns Belviq (increased risk of colorectal, pancreatic, and lung cancers) Fenfluramine (increased risk of valvular disease and pulmonary HTN) Dexfenfluramine (increased risk of valvular disease) Sibutramine (increased risk of heart attack and strokes) Ephedra (increased risk of heart attack and strokes)* Hydroxycitric acid (increased risk of liver failure)** * Used in Hydroxycut until 2004 ** Used in Hydroxycut until 2009 Sympathomimetics MOA: Reduces appetite by ↑ release of NE in CNS Efficacy: 3-4 kg loss with short term use (<12 weeks) Discontinue at 4 weeks if weight loss is unsatisfactory Price/Month: $ ADR: Hypertension Palpitations Tachycardia Agitation Insomnia Constipation Blurry vision Dry mouth Asthenia Tremor Contraindications: Glaucoma History of drug abuse History of ASCVD or pulmonary hypertension Hyperthyroidism Agitated state Concurrent use of other anorectic agents Use of MAOIs within 14 days Hypersensitivity to sympathomimetics Pregnant or Nursing Use Caution: Diabetes ➔ risk of hypoglycemia due to anorectic effect Elderly ➔ risk of dependence, angina, MI, hypertension Hypertension ➔ risk of worsening hypertension and pulse Heart failure ➔ risk of myocardial toxicity Other cardiac diseases ➔ risk of arrhythmias, cardiomyopathy, acute MI Seizure disorder ➔ risk of lowering seizure threshold, unmasking tics Psychiatric disease ➔ risk of insomnia, irritability, anxiety, CNS depression Drugs for Long-Term Use (Chronic) Long-Term Pharmacotherapy Lipase Inhibitor: Orlistat (Alli, Xenical) MOA: Reversibly inhibits gastric & pancreatic lipases needed for food breakdown, thus inhibiting dietary fat absorption by 30% Price/Month: $ [OTC] - $$$ [Rx] Dosing: TID with fatty meal Alli capsules [OTC] Xenical capsules [Rx] Interactions: fat-soluble vitamins, warfarin, cyclosporine ADR: Oily rectal leakage Abdominal pain Flatulence with discharge Bowel urgency Influenza URTI Contraindications: Chronic malabsorption Cholestasis Combination: bupropion/naltrexone (Contrave) MOA: Naltrexone is an opioid antagonist Bupropion weakly inhibits reuptake of NE and DA Weight loss mechanism not well understood Boxed warning: Not approved to treat depression, may increase risk of suicidality in kids & young adults <24 years-old Price/Month: $$ Dosing: Titrate (see image) due to seizure risk Discontinue at 12 weeks if < 5% weight loss ADR: Headache Sleep disturbances N/C/V Contraindications MAOI use within 14 days Chronic opioid or opiate agonist use Acute opioid withdrawal Uncontrolled hypertension History of seizures Bulimia or anorexia nervosa Use with linezolid or IV methylene blue Abrupt discontinuation of alcohol, benzos, barbiturates, or antiepileptic drugs Combination: phentermine/topiramate (Qsymia) MOA: Phentermine ↑ release of NE in CNS Topiramate suppresses appetite and increases satiety, mechanism for topiramate not well understood Price/Month: $$ Dosing: Titrate (see image) due to seizure risk Evaluation #1: abruptly discontinue if 3% weight loss not achieved Evaluation #2: gradually discontinue if 5% weight loss not achieved ADR: Similar to sympathomimetics Contraindications MAOI use within 14 days Glaucoma Hyperthyroidism Pregnancy (REMS* program) Incretin Mimetics MOA for weight loss: analogs of human incretin hormones (GLP-1 ± GIP) which will: slow gastric emptying ↓ food intake ↑ satiety ↑ thermogenesis of adipose tissues Boxed warning: Thyroid C-cell tumor risk Price/Month: $$$ Dosing: Titrate due to GI upset risk Daily [Saxenda] Weekly [Wegovy, Zepbound] Interactions: additive ADR with agents that slow gastric emptying ADR: nausea, vomiting, constipation Contraindications: Personal or family history of medullary thyroid cancer (MTC) Multiple endocrine neoplasia syndrome type 2 (MEN2) Pregnancy (liraglutide only) GI related side effects made worse by large portions and high-fat meals!!!! Increase water intake +/- OTC laxative to reduce constipation Use good, safe subcutaneous injection technique: Store unopened pens in refrigerator After opening, ok to store at room temperature: Saxenda (liraglutide) → 30 days Wegovy (semaglutide) → 28 days Zepbound (tirzepatide) → 21 days Check expiration date & ensure product is clear without particles Clean hands and injection site thoroughly Inject at 90-degree angle into abdomen, back of arm, or thigh Do not rub the injection site Dispose in puncture-proof sharps container GLP-1 Agonist: Liraglutide (Saxenda) Same active ingredient as Victoza for T2DM Reusable pen* with dial-up dose, new pen needle needed for each injection Evaluation strategy: Discontinue if 5% weight loss not achieved at 12 weeks of max tolerated dose or 16 weeks after initiation *Prime before first dose GLP-1 Agonist: Semaglutide (Wegovy) Same active ingredient as Ozempic (SQ injectable) or Rybelsus (oral tablet) for T2DM Single use, prefilled set-dose pens* with hidden needle Evaluation strategy: Discontinue if 5% weight loss not achieved within 3 months *No pen priming necessary GLP-1/GIP Agonist: Tirzepatide (Zepbound) Same active ingredient as Mounjaro for T2DM Single use, prefilled set-dose pens* with hidden needle Evaluation strategy: Unclear, use clinical judgment *No pen priming necessary Natural Products* Barley Bitter orange Blond psyllium Caffeine Chitosan Ephedra/ma huang (banned in US) Garcinia cambogia Green tea extract Guar gum Hoodia Pyruvate St. John’s Wort 5-Hydroxytryptophan *Safety & efficacy are undetermined Medication Reconciliation Drug Class Potential for Weight Gain Neutral or Potential for Weight loss Alpha-Blockers terazosin alfuzosin, doxazosin, tamsulosin Antidepressants MAOIs, mirtazapine, SSRIs, TCAs bupropion, desvenlafxine, venlafaxine Antidiabetics insulins, sulfonylureas, TZDs DPP4s, GLP1s, metformin, SGLT2s Antiphyscotics clozapine, olanzapine, quetiapine, risperidone aripiprazole, haloperidol, ziprasidone Antihypertensives CCBs, some beta-blockers ACEi, ARB, diuretics Bariatric Surgeries 2013 ACC/AHA/TOS Guidelines Bariatric Surgeries Classifications: Restrictive ➔ reduces the size of the stomach to limit amount of food that can be consumed at one time Malabsorptive ➔ bypasses a portion of the intestine to limit nutrient absorption Results: Initial ➔ 48-85% excess body weight lost in 1 to 2 years Maintenance ➔ 25-68% excess body weight loss maintained after 7 years Risks: 30-day mortality rate: 0.3-1.1% Venous thromboembolism Bleeding Anastomotic leaks Wound infections Vitamin B12 and iron deficiency Dumping syndrome: vasomotor due to accelerated emptying of hyperosmolar content into the small intestine (typically after malabsorptive surgeries Post-surgical bariatric multivitamin supplements recommended for life, especially with: Calcium Iron Vitamin B12 Vitamin C Vitamin D Surgery Type Restrictive Malabsorptive 2-Year Wt Loss Comments Adjustable Gastric Band X 45-55% Possible to “cheat” Roux-en-Y Gastric Bypass X X 60-85% Gold standard Sleeve Gastrectomy X 55-80% Difficult to “cheat” Biliopancreatic Diversion + Duodenal Switch Bypass X X 70-80% Complex and risky Lecture Summary Determinants of body weight include genetic, environmental, biological, & behavioral factors The following drug classes have numerous agents that may cause weight gain: corticosteroids, antidiabetics, psychiatric, antihypertensives, & hormonal therapy Lifestyle intervention is recommended for all patients as first line therapy Selection of pharmacologic agents should be based on what the patient has failed, safety, & efficacy toward meeting the patient’s goals