Endocrine

Obesity: pharmacotherapy and bariatric surgery referral

Clinical Overview and When to Suspect Obesity Requiring Treatment Escalation

— Overweight: BMI 25–29.9 kg/m²

— Class I obesity: BMI 30–34.9; Class II: 35–39.9; Class III: ≥40

— Asian populations: lower thresholds (overweight ≥23, obesity ≥27.5) per WHO/ADA risk-based cutoffs

— Waist circumference complements BMI: >102 cm (men) / >88 cm (women) signals visceral adiposity risk independent of BMI

— Recurrent failure of lifestyle-only intervention (≥6 months structured diet/exercise without ≥5% loss)

— Presence of weight-related comorbidities: T2DM, prediabetes, HTN, dyslipidemia, MASLD/NASH, OSA, OA, PCOS, GERD, infertility, depression

— Rapid weight gain after smoking cessation, antipsychotics, insulin, glucocorticoids, or anticonvulsants

— BMI ≥30 alone, or BMI ≥27 with a comorbidity → pharmacotherapy candidate

— BMI ≥40, or ≥35 with comorbidity → bariatric surgery candidate (ASMBS 2022 lowered this to ≥35 regardless of comorbidity, and ≥30 with metabolic disease in selected patients)

— Treat obesity like HTN: titrate therapy, reassess every 3 months, intensify if <5% loss

— Address bias: document obesity as a diagnosis (ICD-10 E66) to justify coverage of pharmacotherapy and surgery

— Screen all adults at every visit (USPSTF Grade B): offer or refer to intensive multicomponent behavioral interventions (≥12 contacts/year) as first step

— Rapid unexplained gain with central obesity, striae, proximal weakness → Cushing

— Cold intolerance, fatigue, bradycardia → hypothyroidism (check TSH)

— Hyperphagia from childhood, hypogonadism → genetic syndromes (Prader-Willi, MC4R)

— Medication-induced gain (review every visit)

Board pearl: A BMI of 27 with T2DM meets criteria for pharmacotherapy; a BMI of 35 alone (no comorbidity) now meets ASMBS criteria for bariatric surgery referral.

Definition and staging (adults, US guidelines):

When to suspect obesity is a treatable chronic disease (not just lifestyle):

Step 3 framing — chronic disease model:

Red flags requiring secondary cause workup before escalation:

Presentation Patterns and Key History

— "I can't lose weight despite dieting" → assess prior attempts, duration, structure, supervised vs unsupervised

— Comorbidity-driven visit: uncontrolled diabetes, refractory HTN, snoring/daytime somnolence, knee pain, infertility, reflux

— Postpartum weight retention, perimenopausal gain, post–smoking cessation gain

— Age of onset (childhood obesity → more refractory, consider genetic)

— Trajectory: gradual vs stepwise (stepwise often medication- or life event–triggered)

— Maximum lifetime weight and lowest sustained adult weight

— Prior interventions: commercial programs, very-low-calorie diets, prior pharmacotherapy (which agents, duration, response, side effects), prior bariatric surgery

— Triggers: pregnancy, injury, depression, job change, medications

— 24-hour recall, meal timing, night eating, binge eating episodes (loss of control, ≥1×/week × 3 months = BED)

— Sugar-sweetened beverages, alcohol calories, ultraprocessed food share

— Physical activity: aim ≥150 min/week moderate-intensity; sedentary time

— Insulin, sulfonylureas, TZDs → switch to GLP-1 RA, SGLT2i, metformin

— Beta-blockers (atenolol, metoprolol) → consider carvedilol or ACEi/ARB

— Atypical antipsychotics (olanzapine, clozapine worst) → aripiprazole, ziprasidone if appropriate

— Gabapentin, pregabalin, mirtazapine, paroxetine, valproate

— Glucocorticoids — taper to lowest dose

— PHQ-9, GAD-7, history of eating disorders, trauma, substance use, alcohol (relative contraindication if uncontrolled)

— Social support, food security, ability to attend follow-up

Step 3 management: Before adding a weight-loss drug, deprescribe or substitute obesogenic medications — this single step can yield 3–5% loss and improves pharmacotherapy response.

Chief complaint clues on Step 3:

Structured weight history (the "obesity-focused HPI"):

Dietary and activity assessment:

Medication review — "obesogenic" drugs to swap when possible:

Psychosocial screening (mandatory before surgery referral):

Physical Exam Findings and Body Composition Assessment

— Height, weight, BMI (auto-calculated)

— Waist circumference at iliac crest, end of normal expiration; >102 cm M / >88 cm F = elevated cardiometabolic risk even at "normal" BMI

— Waist-to-height ratio >0.5 = increased risk (simple, robust across ethnicities)

— Neck circumference >17 in (M) / >16 in (F) → screen for OSA

— BP cuff must be appropriately sized (large adult or thigh cuff); undersized cuff falsely elevates BP by 10–20 mmHg → spurious "resistant HTN"

— Resting tachycardia may reflect deconditioning, OSA, or stimulant use

— SpO₂ on room air; consider overnight oximetry if <94% awake

— Skin: acanthosis nigricans (insulin resistance), skin tags, intertrigo, hidradenitis, purple striae >1 cm (Cushing), hirsutism (PCOS)

— Neck: thyromegaly, buffalo hump, Mallampati class III–IV (OSA risk, airway planning for surgery)

— Cardiopulmonary: loud P2, elevated JVP (pulmonary HTN from OSA/OHS), bibasilar crackles

— Abdomen: hepatomegaly (MASLD), prior surgical scars (adhesions affect bariatric approach), umbilical/incisional hernias

— MSK: genu varum/valgus, knee/hip OA, lumbar pain

— Lower extremities: venous stasis, lymphedema, pretibial edema, skin breakdown

— Mental status: flat affect, anhedonia → screen depression

— Functional capacity in METs (climb 1 flight without stopping ≈ 4 METs — favorable)

— Frailty assessment in older adults

— Airway exam (short neck, large tongue) — anticipate difficult intubation

Key distinction: Acanthosis nigricans signals insulin resistance and predicts strong response to metformin + GLP-1 RA, whereas violaceous striae, proximal myopathy, and moon facies demand a Cushing workup before labeling as primary obesity.

Anthropometrics — measure at every visit:

Vital signs caveats:

Targeted exam for comorbidities and secondary causes:

Hemodynamic and surgical-risk assessment when surgery is being considered:

Diagnostic Workup — Initial Labs and Comorbidity Screening

— Fasting glucose + HbA1c — screen T2DM/prediabetes (USPSTF: screen 35–70 if overweight/obese)

— Lipid panel — fasting or non-fasting

— ALT/AST — if elevated or BMI ≥30, calculate FIB-4; if FIB-4 ≥1.3 → vibration-controlled transient elastography (FibroScan) for MASLD fibrosis staging (AASLD 2023)

— TSH — rule out hypothyroidism

— Creatinine + eGFR, urine albumin/creatinine ratio — especially with diabetes/HTN

— CBC, basic metabolic panel

— 25-OH vitamin D, B12, iron studies, ferritin — baseline before bariatric surgery (deficiencies common pre-op)

— Uric acid if gout history

— OSA: STOP-BANG ≥3 → polysomnography or home sleep apnea test; mandatory before bariatric surgery

— Cushing: if features present → late-night salivary cortisol ×2, or 1-mg dexamethasone suppression

— PCOS in women with oligomenorrhea + hirsutism → total/free testosterone, DHEAS, pelvic US

— Hypogonadism in men with BMI ≥40 → morning total testosterone (often low; weight loss raises it)

— Depression: PHQ-9; binge eating disorder: brief BED screen

— ASCVD 10-year risk calculator; consider coronary artery calcium score if intermediate risk

— ECG if ≥40 with comorbidities or pre-op

— BNP if dyspnea (obesity falsely lowers BNP — interpret cautiously)

— H. pylori testing (institutional variation)

— Upper endoscopy if reflux symptoms

— Pregnancy test in reproductive-age women

— HbA1c goal <8% pre-op when feasible

Board pearl: FIB-4 ≥1.3 in a patient with obesity is the Step 3 trigger to refer for noninvasive fibrosis staging — do not just repeat LFTs and watch.

Baseline labs for every adult with obesity (BMI ≥30, or ≥25 with risk):

Targeted screening based on findings:

Cardiovascular risk:

Pre-bariatric specific:

Diagnostic Workup — Advanced Studies and Pre-Surgical Evaluation

— Rapid weight gain (>5 kg in 1–3 months) without dietary change

— Central obesity with proximal myopathy, easy bruising, hypokalemia → 24-hr urinary free cortisol, late-night salivary cortisol, 1-mg dexamethasone suppression

— Early-onset severe obesity (<5 years old), hyperphagia, developmental delay → genetic testing (MC4R most common monogenic; leptin, POMC, LEPR; consider setmelanotide candidacy for POMC/LEPR/Bardet-Biedl)

— Galactorrhea, amenorrhea → prolactin, MRI pituitary

— Severe hypogonadism without weight loss response → karyotype if features of Klinefelter

— DXA: lean vs fat mass; useful in sarcopenic obesity (older adults), monitoring high-dose GLP-1 RA (concern for excessive lean mass loss)

— Bioelectrical impedance — office-based proxy

— Medical: cardiology clearance if known CAD, prior MI, or significant risk; pulmonology if OSA/OHS; gastroenterology for EGD if symptomatic

— Nutrition: registered dietitian assessment, 3–6 months documented preoperative weight management (insurance-driven, not evidence-based, but commonly required)

— Behavioral health: psychological/psychiatric evaluation — assess capacity to adhere, screen untreated BED, active substance use, suicidality, unstable psychiatric illness

— Anesthesia: airway evaluation, OSA optimization with CPAP

— Imaging: abdominal US if gallstones suspected (rapid weight loss → gallstones)

— Suspected pulmonary HTN (OSA/OHS), unexplained dyspnea, prior cardiotoxic exposure

— Obesity cardiomyopathy suspected (eccentric LVH, diastolic dysfunction)

Step 3 management: A 42-year-old with BMI 46, T2DM, OSA on CPAP, and stable depression on SSRI is an appropriate bariatric candidate — psychiatric illness must be stable and treated, not absent.

When to pursue advanced metabolic/endocrine workup:

Body composition (when relevant, not routine):

Comprehensive pre-bariatric workup (multidisciplinary):

Echocardiography indications:

Treatment Framework and Stepped-Care Logic

— Intensive behavioral therapy: ≥14 sessions over 6 months (Medicare covers in primary care for BMI ≥30)

— Diet: 500–750 kcal/day deficit; Mediterranean, DASH, or low-carb all acceptable — adherence > specific composition

— Physical activity: 150–300 min/week moderate aerobic + 2 days resistance training

— Sleep: 7–9 hours; treat OSA

— Behavioral: self-monitoring (food log, weight, steps), stimulus control, cognitive restructuring

— Step 1 (BMI ≥25): lifestyle + behavioral intervention × 3–6 months; goal ≥5% loss

— Step 2 (BMI ≥30, or ≥27 with comorbidity, OR <5% loss on lifestyle): add pharmacotherapy

— Step 3 (BMI ≥35, or ≥30 with metabolic disease per ASMBS 2022; classic CMS: BMI ≥35 with comorbidity or ≥40): refer for bariatric/metabolic surgery

— Step 4 (post-surgery weight regain or inadequate response): revisional surgery, add pharmacotherapy (GLP-1 RA highly effective post-op)

— 3–5% loss → improves glycemia, TGs, BP

— 5–10% → improves OSA, MASLD, HbA1c by ~0.5–1%

— ≥10% → may induce T2DM remission, durable HTN improvement

— ≥15–20% → near-bariatric-level metabolic benefit (achievable with semaglutide 2.4 mg, tirzepatide)

— <5% loss → intensify (switch/add drug, refer to surgery, evaluate adherence)

— ≥5% → continue indefinitely (obesity is chronic; stopping causes regain)

Board pearl: Stopping anti-obesity pharmacotherapy after 1 year causes two-thirds of weight to return within a year (STEP-4, SURMOUNT-4) — counsel patients up front that therapy is long-term, like antihypertensives.

Foundation for all patients (the "always-on" layer):

Stepped-care decision tree:

Goal-setting (Step 3-style realistic targets):

Reassess at 3 months on any therapy:

Pharmacotherapy — First-Line and Preferred Agents

— Semaglutide 2.4 mg SC weekly (Wegovy): GLP-1 RA. Mean loss ~15% at 68 weeks (STEP trials). Titrate 0.25 → 0.5 → 1.0 → 1.7 → 2.4 mg over 16 weeks. Also reduces MACE in patients with CVD + obesity without diabetes (SELECT trial — landmark).

— Tirzepatide 15 mg SC weekly (Zepbound): dual GIP/GLP-1 agonist. Mean loss ~21% at 72 weeks (SURMOUNT-1). Currently most efficacious approved agent. Titrate monthly: 2.5 → 5 → 7.5 → 10 → 12.5 → 15 mg.

— Liraglutide 3 mg SC daily (Saxenda): older GLP-1 RA; ~8% loss; daily injection limits adherence.

— Phentermine/topiramate ER (Qsymia): ~9% loss; contraindicated in pregnancy (topiramate teratogen — cleft palate), hyperthyroidism, glaucoma, recent MAOI. Topiramate → paresthesias, cognitive slowing, kidney stones.

— Naltrexone/bupropion (Contrave): ~5% loss; avoid in seizure disorder, uncontrolled HTN, chronic opioid use (precipitates withdrawal).

— Orlistat 120 mg TID: ~3% loss; lipase inhibitor → steatorrhea, fat-soluble vitamin deficiency. Useful when injectables contraindicated.

— Phentermine alone: sympathomimetic, short-term (≤12 weeks per FDA label, though commonly used longer off-label). Avoid in CAD, uncontrolled HTN, hyperthyroidism, MAOI.

— Personal/family history of medullary thyroid carcinoma or MEN2 (boxed warning)

— History of pancreatitis — relative caution

— Severe gastroparesis — avoid; can worsen

— Pregnancy — stop ≥2 months before conception (semaglutide long half-life)

Step 3 management: In a patient with obesity, established ASCVD, and no diabetes, choose semaglutide 2.4 mg — it has FDA indication for MACE reduction (SELECT) on top of weight loss.

Indications: BMI ≥30, or ≥27 with weight-related comorbidity, after lifestyle trial. All require ongoing lifestyle therapy.

Preferred first-line (2024 US practice) — incretin-based agents:

Oral options:

GLP-1 RA contraindications/cautions:

Common AEs: nausea, vomiting, constipation, gallstones with rapid loss, injection-site reactions. Titrate slowly; hydrate.

Bariatric/Metabolic Surgery — Indications, Procedures, and Referral

— BMI ≥35 regardless of comorbidities

— BMI 30–34.9 with metabolic disease (especially T2DM not at goal)

— Asian patients: lower BMI thresholds (≥27.5 with comorbidity)

— Pediatric: ≥13 years with BMI ≥120% of 95th percentile + comorbidity, or ≥140% alone (AAP 2023)

— Active substance use disorder, uncontrolled severe psychiatric illness, inability to adhere to lifelong follow-up/supplementation

— Active malignancy, end-stage organ disease without transplant plan

— Pregnancy or planned within 12–18 months

— Sleeve gastrectomy (most common in US): removes 75–80% of stomach along greater curvature. EWL ~25–30% TBWL. Lower nutrient deficiency risk; worsens GERD (relative contraindication if severe GERD/Barrett). Restrictive + hormonal (drops ghrelin).

— Roux-en-Y gastric bypass: small gastric pouch + jejunal Roux limb. ~30–35% TBWL. Best for severe GERD, severe T2DM (highest diabetes remission ~60–75%). Risks: dumping syndrome, marginal ulcer, internal hernia, more micronutrient deficiencies (iron, B12, Ca, vit D).

— Adjustable gastric band: largely abandoned (poor durability, band slippage/erosion).

— Biliopancreatic diversion with duodenal switch (BPD/DS) and SADI-S: highest weight loss (~40% TBWL) and diabetes remission; highest nutritional risk; reserved for BMI ≥50.

— Endoscopic options: intragastric balloon, endoscopic sleeve gastroplasty — bridge or alternative for lower BMI/those declining surgery.

— T2DM remission, HTN improvement, OSA resolution, MASLD regression

— Mortality reduction ~30–50% over 10 years vs matched controls (SOS, Swedish cohort)

— 30-day mortality ~0.1–0.3% (lower than cholecystectomy in experienced centers)

CCS pearl: Post–gastric bypass patient with persistent tachycardia >120 and abdominal pain on POD 1–3 → suspect anastomotic leak; order CT with oral contrast or take to OR — do not wait for fever or peritonitis.

Indications (ASMBS/IFSO 2022 — current Step 3 standard):

Contraindications:

Procedures:

Outcomes:

Early complications: anastomotic leak (tachycardia is earliest sign — CCS pearl), bleeding, VTE

Late complications: stricture, marginal ulcer (avoid NSAIDs lifelong post-RYGB), internal hernia (acute abdominal pain after RYGB → CT, surgical exploration), dumping, nutritional deficiencies, alcohol use disorder (de novo)

Special Populations — Elderly and Renal/Hepatic Impairment

— Obesity in this group is associated with disability and frailty more than mortality (obesity paradox in some cohorts)

— Sarcopenic obesity is the key concern: rapid weight loss can worsen lean mass, bone density, falls

— Combine caloric deficit with resistance training and adequate protein (1.0–1.2 g/kg/day)

— Lifestyle + protein + resistance training is first-line

— GLP-1 RA and tirzepatide effective; monitor for excessive lean mass loss, dehydration, hypoglycemia (if on sulfonylurea/insulin — reduce these)

— Phentermine generally avoided (CV risk, insomnia, BPH worsening)

— Bariatric surgery: age alone is not a contraindication; outcomes acceptable up to 70+ in selected, functional patients; higher perioperative morbidity — individualize

— Semaglutide and liraglutide: no dose adjustment; semaglutide reduces albuminuria and slows eGFR decline (FLOW trial in T2DM + CKD)

— Tirzepatide: no renal dose adjustment; limited data in severe CKD

— Orlistat: can cause oxalate nephropathy and AKI — avoid in CKD

— Phentermine/topiramate: topiramate increases kidney stone risk; avoid in eGFR <30; adjust in moderate impairment

— Naltrexone/bupropion: avoid in ESRD; reduce dose in moderate impairment

— Bariatric surgery improves eGFR trajectory and is considered before transplant in obesity-related CKD

— MASLD/MASH is an indication to treat obesity aggressively

— Semaglutide improves MASH histology (ESSENCE trial); reduces hepatic fat

— Tirzepatide also improves MASH endpoints

— Resmetirom (thyroid hormone receptor-β agonist) now approved for MASH F2–F3 — adjunct, not weight-loss drug

— Avoid orlistat in cholestasis

— Naltrexone/bupropion: caution; bupropion lowers seizure threshold and is hepatically metabolized

— In decompensated cirrhosis: weight loss drugs limited; bariatric surgery only at experienced transplant centers

Board pearl: In a patient with obesity, T2DM, and CKD with albuminuria, semaglutide is the preferred anti-obesity agent — weight loss plus renal and cardiovascular benefit.

Older adults (≥65):

Chronic kidney disease:

Hepatic impairment:

Special Populations — Pregnancy, Reproductive Age, and Pediatrics

— Obesity → anovulation, infertility, miscarriage, gestational diabetes, preeclampsia, macrosomia, cesarean, stillbirth

— 5–10% weight loss often restores ovulation in PCOS

— Counsel reliable contraception on any anti-obesity pharmacotherapy

— GLP-1 RAs and tirzepatide: stop ≥2 months before conception (semaglutide half-life ~1 week, full clearance ~5–6 weeks); animal data show teratogenicity

— Topiramate: teratogen — cleft lip/palate; avoid in pregnancy and use effective contraception

— Orlistat: not recommended (fat-soluble vitamin malabsorption)

— Bariatric surgery improves fertility — avoid pregnancy for 12–18 months post-op to prevent fetal nutrient deficiency during rapid loss

— No anti-obesity pharmacotherapy in pregnancy

— Weight gain targets (IOM): BMI 25–29.9 → 15–25 lb; BMI ≥30 → 11–20 lb

— Screen for GDM early (1st trimester A1c) and repeat at 24–28 weeks

— Daily folate 400–800 mcg; consider higher in prior NTD or on certain anticonvulsants

— Avoid oral contraceptives after malabsorptive procedures (reduced absorption) — use IUD, implant, or injectable

— Screen for and treat iron, B12, folate, vitamin D, calcium, thiamine deficiencies

— Dumping syndrome makes standard 75-g OGTT unreliable post-RYGB → use fasting glucose + A1c + home glucose monitoring

— Intensive health behavior and lifestyle treatment (≥26 contact hours over 3–12 months) for ages ≥6

— Pharmacotherapy considered at age ≥12 with obesity (orlistat, liraglutide 3 mg, semaglutide 2.4 mg, phentermine/topiramate approved in adolescents)

— Bariatric surgery referral at ≥13 with severe obesity meeting criteria

— Screen for T2DM, dyslipidemia, HTN, MASLD, OSA, depression

Step 3 management: A 28-year-old on semaglutide who reports she wants to conceive → stop semaglutide, start folate, ensure reliable contraception, and delay conception ≥2 months after last dose.

Reproductive-age women:

Pregnancy itself:

Post-bariatric pregnancy:

Pediatrics (AAP 2023 — paradigm shift):

Complications and Adverse Outcomes

— Cardiometabolic: T2DM, HTN, dyslipidemia, ASCVD, HF (HFpEF especially), AF, stroke

— Pulmonary: OSA, obesity hypoventilation syndrome (OHS — PaCO₂ >45), pulmonary HTN, asthma

— GI: MASLD/MASH/cirrhosis, GERD, cholelithiasis

— Renal: CKD, nephrolithiasis, albuminuria

— MSK: OA (knee, hip), low back pain, gout

— Endocrine/reproductive: PCOS, infertility, hypogonadism in men

— Oncologic: endometrial, breast (postmenopausal), colorectal, esophageal adenocarcinoma, pancreatic, RCC, hepatocellular, gallbladder, ovarian, thyroid, multiple myeloma — 13 obesity-associated cancers per CDC

— Neuropsychiatric: depression, anxiety, idiopathic intracranial hypertension, dementia risk

— Skin: intertrigo, hidradenitis, lymphedema

— GLP-1 RA/tirzepatide: N/V/D, constipation, acute pancreatitis (rare), cholelithiasis with rapid loss (consider prophylactic ursodiol 600 mg/day post-bariatric or with rapid loss), gastroparesis exacerbation, injection site reactions, transient HR increase; possible thyroid C-cell tumors (rodent data; avoid in MTC/MEN2)

— Phentermine/topiramate: paresthesias, metabolic acidosis, kidney stones, cognitive fog, teratogen

— Naltrexone/bupropion: insomnia, dry mouth, seizures, opioid withdrawal in opioid users, suicidality (boxed warning)

— Orlistat: steatorrhea, fecal urgency, fat-soluble vitamin deficiency (supplement A/D/E/K)

— Anastomotic/staple-line leak, bleeding, VTE/PE (leading cause of 30-day mortality), wound infection, rhabdomyolysis (long OR, large body habitus)

— Nutritional deficiencies: iron, B12, folate, thiamine (especially with intractable vomiting → Wernicke), calcium, vitamin D, copper, zinc, fat-soluble vitamins (BPD/DS)

— Dumping syndrome (early — osmotic; late — reactive hypoglycemia)

— Marginal ulcer after RYGB (smoking and NSAIDs are key risks)

— Internal hernia (RYGB) — acute postprandial pain, can be intermittent; CT may miss; low threshold for laparoscopy

— Stricture, SBO, cholelithiasis, kidney stones (oxalate)

— Bone loss, fractures

— De novo alcohol use disorder post-RYGB (altered pharmacokinetics, faster intoxication)

— Weight regain in 20–30% by 5–10 years

Board pearl: Post-RYGB patient with confusion, ataxia, ophthalmoplegia after persistent vomiting → Wernicke encephalopathy — give IV thiamine before any glucose.

Complications of untreated obesity:

Pharmacotherapy adverse effects:

Bariatric surgery — early (<30 d):

Bariatric — late:

When to Escalate Care — Specialist Referral and Inpatient Triage

— <5% weight loss after 3–6 months of pharmacotherapy at maximum tolerated dose

— Multiple drug intolerances or contraindications

— Complex obesity with binge eating disorder, severe psychiatric comorbidity, polypharmacy

— Post-bariatric weight regain or nutritional deficiency

— BMI ≥35 (any patient), or ≥30 with uncontrolled T2DM or other metabolic disease (ASMBS 2022)

— Inadequate response to pharmacotherapy

— Patient preference after counseling

— Suspected Cushing, hypothyroidism not responding to replacement, suspected monogenic obesity, refractory T2DM

— Setmelanotide candidacy (POMC, LEPR, PCSK1 deficiency, Bardet-Biedl)

— Sleep medicine: STOP-BANG ≥3, witnessed apneas, refractory HTN, daytime somnolence

— Cardiology: suspected HFpEF, AF, ASCVD, pre-op clearance

— Hepatology: FIB-4 ≥1.3 with confirmed fibrosis, suspected MASH

— Psychiatry/psychology: BED, depression, pre-bariatric evaluation

— Registered dietitian: every patient; MNT is covered by Medicare for diabetes and CKD

— Acute pancreatitis on GLP-1 RA → admit, NPO, IV fluids, hold GLP-1, evaluate for other causes (stones, alcohol, hyperTG)

— Post-op tachycardia, abdominal pain, fever → readmit, CT, surgical consult — leak until proven otherwise

— Severe vomiting post-bariatric → admit for IV fluids, thiamine empirically before dextrose, electrolytes, evaluate for stricture/obstruction

— Acute abdominal pain after RYGB → urgent imaging and surgical consult for internal hernia

— Post-bariatric hypoglycemia (late dumping) → 75-g mixed-meal test, dietary changes, acarbose, octreotide for refractory cases

— Severe AKI on orlistat → discontinue, hydrate, evaluate oxalate nephropathy

CCS pearl: Any bariatric post-op patient with HR >120 even with normal labs and imaging warrants observation, repeat imaging, and surgical consultation — tachycardia is the most sensitive early sign of a leak.

Refer to obesity medicine specialist:

Refer to bariatric surgery (multidisciplinary program):

Refer to endocrinology:

Refer to other specialists:

Inpatient/ED triage (CCS scenarios):

Key Differentials — Same-Category (Secondary Causes of Weight Gain)

— Hypothyroidism: modest gain (5–10 lb), fatigue, cold intolerance, constipation, bradycardia → TSH (treat with levothyroxine; weight loss is modest, ~5–10% of body weight at most)

— Cushing syndrome: central obesity, moon facies, dorsocervical fat pad, purple striae >1 cm, proximal myopathy, easy bruising, hypokalemia, glucose intolerance → late-night salivary cortisol ×2, 1-mg dexamethasone suppression, 24-hr UFC; then ACTH to localize

— Hypothalamic obesity: post-craniopharyngioma surgery, TBI, infiltrative disease → hyperphagia, often rapid gain; consider setmelanotide trials

— Insulinoma: weight gain from frequent eating to prevent hypoglycemia; Whipple triad

— Polycystic ovary syndrome: oligomenorrhea, hirsutism, acne, infertility; metformin and GLP-1 RA helpful

— Growth hormone deficiency in adults: increased central fat, decreased lean mass

— Pseudohypoparathyroidism (Albright): short stature, round facies, brachydactyly

— Antipsychotics (olanzapine, clozapine, quetiapine, risperidone)

— Antidepressants (mirtazapine, paroxetine, TCAs)

— Antiepileptics (valproate, gabapentin, pregabalin, carbamazepine)

— Glucocorticoids

— Insulin, sulfonylureas, TZDs (pioglitazone)

— Beta-blockers (especially non-vasodilating)

— Hormonal contraceptives (modest)

— Antihistamines (chronic)

— MC4R deficiency — most common monogenic

— Leptin, LEPR, POMC, PCSK1 deficiencies — setmelanotide-responsive

— Prader-Willi: hypotonia, hyperphagia after age 2, hypogonadism, intellectual disability

— Bardet-Biedl: retinitis pigmentosa, polydactyly, renal anomalies

— Albright hereditary osteodystrophy, Alström, Cohen, fragile X

Key distinction: Hypothyroidism causes only modest gain; if a patient blames their obesity on a normal-TSH thyroid, do not treat empirically with levothyroxine — this is a Step 3 trap.

Before labeling weight gain as primary obesity, exclude treatable secondary causes — especially with rapid onset, atypical features, or poor response to standard therapy.

Endocrine causes:

Medication-induced weight gain (must always review):

Genetic/syndromic obesity (consider in early-onset, severe, hyperphagia):

Key Differentials — Other-Category Mimics and Weight-Related Symptom Mimics

— Deconditioning (most common)

— OSA / obesity hypoventilation syndrome

— HFpEF — common in obesity; BNP may be falsely low; consider echo with diastolic indices

— Asthma/COPD (overdiagnosed in obesity due to dyspnea on exertion)

— Pulmonary embolism — obesity is a major risk factor; do not anchor on "deconditioning"

— Pulmonary hypertension secondary to OSA/OHS

— Lipedema vs lymphedema vs venous insufficiency vs HF

— Lipedema: symmetric, painful, spares feet (positive cuff sign), women, family history — does not respond well to weight loss alone; refer to lymphatic specialist

— Lymphedema: non-pitting, feet involved, Stemmer sign positive

— Right HF, cirrhosis, nephrotic syndrome — work up appropriately

— OSA, OHS, depression, hypothyroidism, iron-deficiency anemia, sleep deprivation, diabetes

— Don't assume "just obesity"

— Marginal ulcer, internal hernia, gallstones, kidney stones, SBO, intussusception, candy cane syndrome, chronic mesenteric ischemia, dumping syndrome

— Pregnancy in reproductive-age women — always test

— Late dumping/post-bariatric hypoglycemia (reactive, 1–3 hrs postprandial)

— Differentiate from insulinoma (fasting hypoglycemia, elevated insulin/C-peptide with low glucose during fast) — uncommon but missed if not considered

— Adherence issues, dose not titrated, obesogenic medications not addressed

— Undiagnosed Cushing, hypothyroidism

— Eating disorder (BED, night eating)

— Sleep deprivation

— Quit-smoking gain (still trending up)

Board pearl: A patient with symmetric, painful lower-extremity "fat" sparing the feet that does not respond to weight loss has lipedema, not obesity-related lymphedema or "stubborn fat" — refer for manual lymphatic drainage and compression; pharmacotherapy alone won't fix it.

When obesity-attributed symptoms appear, ensure you are not missing a separate diagnosis.

Dyspnea in obesity — differentials:

Edema in obesity:

Fatigue in obesity:

Abdominal pain post-bariatric — broad differential:

Hypoglycemia post-bariatric:

"Failure to lose weight" mimics:

Secondary Prevention, Long-Term Pharmacotherapy, and Discharge Planning

— Obesity treatment is lifelong, like HTN or T2DM

— Stopping pharmacotherapy or skipping post-bariatric follow-up → regain and comorbidity recurrence

— Plan for indefinite maintenance dosing once goal achieved

— Continue at effective dose; some patients can step down semaglutide/tirzepatide cautiously, but most need full dose

— Annual reassessment of efficacy, tolerability, comorbidities

— Switch agent if <5% loss at 3–6 months despite adherence and titration

— Lifelong micronutrient supplementation:

— Bariatric multivitamin (2 tabs/day post-sleeve or 1–2 post-RYGB)

— Calcium citrate 1200–1500 mg/day in divided doses

— Vitamin D 3000 IU/day (titrate to level >30 ng/mL)

— Vitamin B12 (500 mcg SL daily or 1000 mcg IM monthly post-RYGB)

— Iron 45–60 mg elemental daily (more in menstruating women)

— Thiamine if any vomiting

— Add A, E, K and zinc/copper monitoring for BPD/DS

— Avoid NSAIDs lifelong after RYGB (marginal ulcer risk); use acetaminophen, topical agents

— Limit alcohol — heightened intoxication, AUD risk

— PPI prophylaxis ×6–12 months post-RYGB (marginal ulcer prevention)

— Ursodiol 600 mg/day ×6 months to prevent gallstones during rapid loss

— Maintain statin per ASCVD risk

— Antihypertensives — anticipate dose reductions as weight falls

— Diabetes meds — taper sulfonylureas and insulin first to avoid hypoglycemia

— Aspirin per usual indications

— Annual ASCVD risk recalculation

Step 3 management: A patient achieving 18% weight loss on tirzepatide who asks to stop because "I've reached my goal" should be counseled that discontinuation causes regain of two-thirds of lost weight within a year; recommend continuation, possibly at maintenance dose.

Chronic disease model — communicate at the start:

Pharmacotherapy maintenance:

Post-bariatric long-term plan:

Cardiometabolic secondary prevention:

Cancer screening: maintain age-appropriate; obesity raises risk for 13 cancers — do not skip colonoscopy, mammography, cervical screening

Vaccinations: influenza, pneumococcal, COVID, RSV per age; hepatitis B if undergoing surgery

Mental health: continue depression/BED treatment; monitor for de novo substance use post-bariatric

Follow-Up, Monitoring Parameters, and Counseling Cadence

— Monthly ×3 during titration (assess GI tolerance, BP, HR, glucose if diabetic, adherence)

— Every 3 months until stable (weight, comorbidity control, side effects)

— Every 6–12 months once stable

— At each visit: weight, BP, HR, A1c if diabetic, lipid q6–12 mo, LFTs annually, renal function annually, vitamin D and B12 if on chronic therapy

— Mental health screen (PHQ-9, BED screen) at least annually

— Reduce/discontinue sulfonylureas and insulin proactively to avoid hypoglycemia

— Hold for severe vomiting, suspected pancreatitis, before elective surgery (anesthesia guidance: hold ≥1 week of weekly injectable due to gastroparesis/aspiration risk — emerging ASA guidance)

— Assess injection technique

— Counsel on muscle preservation: protein 1.2–1.5 g/kg/day, resistance training 2×/week

— 1–2 weeks, 1, 3, 6, 9, 12 months in year 1

— Every 6 months in year 2

— Annually thereafter — lifelong

— Labs at 3, 6, 12 months then annually: CBC, CMP, iron studies, ferritin, B12, folate, vitamin D, PTH, thiamine, A1c, lipids; copper/zinc/vit A/E/K for BPD/DS

— DXA at 2 years and periodically (bone loss)

— Annual screening for AUD, depression, suicidality

— Realistic goals: ≥5% improves health; ≥10% transformative

— Self-monitoring: weight 1–2×/week, food log, step count

— Sleep hygiene, stress management, limit ultraprocessed food

— Plateau is normal; weight loss is not linear

— Anti-obesity medications and surgery are tools, not failures of willpower — addresses bias and improves adherence

— Begin where the patient is; aim for 150 → 300 min/week

— Add resistance training 2 days/week to preserve lean mass

— For post-bariatric patients: walking POD 1, gradual return to full activity by 4–6 weeks

Board pearl: In any patient with persistent vomiting after bariatric surgery, empirically give thiamine before glucose-containing IV fluids to prevent Wernicke encephalopathy — this single decision is a frequent Step 3 vignette.

Pharmacotherapy follow-up schedule:

GLP-1 RA / tirzepatide specific monitoring:

Post-bariatric follow-up cadence (multidisciplinary):

Patient counseling pillars:

Activity progression:

Ethical, Legal, and Patient Safety Considerations

— Use person-first language ("patient with obesity," not "obese patient")

— Avoid moralizing; obesity is a chronic disease with genetic, biological, environmental, and behavioral contributors

— Bias from clinicians worsens outcomes: patients delay care, doctor-shop, and disengage

— Appropriately sized equipment (gowns, BP cuffs, exam tables, scales) is a patient safety and dignity issue

— Must include: realistic weight-loss expectations, lifelong supplementation, lifelong follow-up, alcohol use risk, pregnancy planning (avoid 12–18 months), revision risk, lifelong NSAID avoidance after RYGB, possibility of regain, surgical mortality risk

— Capacity assessment required — untreated severe psychiatric illness or active substance use precludes informed consent and surgical candidacy

— Adolescents (AAP 2023): assent from adolescent + consent from guardian; multidisciplinary evaluation mandatory

— Patients with intellectual disability: surrogate decision-maker; ensure substantial benefit and ability to adhere with caregiver support

— Off-label and cosmetic use of GLP-1 RAs in non-obese patients diverts supply from patients with diabetes or obesity who need it — counsel against and adhere to FDA-approved indications

— Compounded semaglutide/tirzepatide: safety concerns, FDA warnings about dosing errors, unverified ingredients — counsel patients against compounded versions when branded available

— Insurance access disparities: discuss prior authorization, patient assistance programs

— Bariatric surgical patient moving or losing insurance: ensure handoff to a bariatric-aware primary care clinician, lab schedule communicated, supplement list reconciled

— Hospitalized post-bariatric patient: flag the chart — no NSAIDs, no large pills (use crushable forms), thiamine before glucose if vomiting, DVT prophylaxis essential (high VTE risk)

— Anesthesia/peri-op: hold weekly GLP-1 RA ≥1 week pre-op for elective surgery (aspiration risk from delayed gastric emptying)

— Suspected child or adolescent neglect contributing to severe pediatric obesity is not typically reportable unless there is clear medical neglect of a treatable life-threatening condition with refusal of care

— Suicidality screen positive on naltrexone/bupropion → immediate safety assessment, consider discontinuation

Step 3 management: A patient post-RYGB admitted for a fracture and given ibuprofen by the inpatient team — your role is to stop the NSAID, switch to acetaminophen ± short-course opioid, and document the lifelong NSAID contraindication prominently.

Weight bias and stigma:

Informed consent for bariatric surgery (Step 3 edge cases):

Pharmacotherapy ethical issues:

Transitions of care (high-yield Step 3):

Mandatory reporting / safety:

High-Yield Associations and Rapid-Fire Clinical Facts

— Pharmacotherapy: BMI ≥30, or ≥27 + comorbidity

— Bariatric surgery (ASMBS 2022): BMI ≥35, or ≥30 + metabolic disease

— Adolescent surgery: BMI ≥120% of 95th %ile + comorbidity, or ≥140%

— Tirzepatide 15 mg: ~21%

— Semaglutide 2.4 mg: ~15%

— Phentermine/topiramate: ~9%

— Liraglutide 3 mg: ~8%

— Naltrexone/bupropion: ~5%

— Orlistat: ~3%

— Bariatric surgery: 25–35% (RYGB, sleeve); BPD/DS up to 40%

— Obesity + ASCVD, no diabetes → semaglutide 2.4 mg (SELECT — MACE reduction)

— Obesity + T2DM → tirzepatide or semaglutide

— Obesity + migraines or seizures → phentermine/topiramate (topiramate helps both)

— Obesity + tobacco use disorder or depression → naltrexone/bupropion (bupropion benefits)

— Obesity + opioid use → avoid naltrexone/bupropion

— Obesity + medullary thyroid cancer / MEN2 → avoid GLP-1 RA / tirzepatide

— Obesity + severe GERD → RYGB > sleeve

— Obesity + uncontrolled T2DM → RYGB for highest remission

— Sleeve worsens GERD; RYGB improves it

— Marginal ulcer: smoking + NSAIDs post-RYGB

— Internal hernia: postprandial pain, RYGB

— Wernicke: thiamine before glucose

— Dumping early (osmotic, 15–30 min) vs late (reactive hypoglycemia, 1–3 hr)

— Ursodiol 6 mo prevents gallstones during rapid loss

— Avoid pregnancy 12–18 mo post-op

— Adults BMI ≥30 → refer for intensive multicomponent behavioral intervention (Grade B)

— Medicare covers Intensive Behavioral Therapy in primary care for BMI ≥30 (face-to-face, weekly ×1 mo, then every other week ×5 mo, then monthly if ≥3 kg loss)

— 5% → glycemia, TG, BP improve

— 10% → OSA, MASLD, A1c by ~1%

— 15% → durable T2DM remission possible

Board pearl: "Best drug for obesity + ASCVD without diabetes" → semaglutide 2.4 mg (Wegovy) — only anti-obesity drug with FDA indication for MACE reduction.

Indication thresholds (memorize):

Efficacy hierarchy (mean TBWL at 1–1.5 yrs):

Choose-the-drug pearls:

Bariatric quick facts:

USPSTF / Medicare:

Comorbidity benefits of weight loss:

Board Question Stem Patterns

— 38-yo F, BMI 31, prediabetes A1c 6.0%, on lifestyle ×6 months with 2% loss. Next step? → Add pharmacotherapy (meets BMI ≥30 or ≥27 + comorbidity threshold)

— BMI 34, prior MI, no diabetes → semaglutide 2.4 mg (SELECT)

— BMI 38, T2DM A1c 9%, on metformin → tirzepatide or semaglutide, consider bariatric referral

— BMI 32, migraines, seizure-free epilepsy → topiramate component appealing → phentermine/topiramate

— BMI 33, smoker who wants to quit, depression → naltrexone/bupropion (caution suicidality screen)

— Pregnant patient with BMI 34 → no drug; nutritional counseling

— BMI 36, no comorbidity, failed lifestyle and 2 drug trials → bariatric surgery referral (ASMBS 2022)

— BMI 32, T2DM A1c 9% despite multi-drug regimen → metabolic surgery referral

— POD 2 RYGB, HR 130, mild abdominal pain, normal WBC → anastomotic leak; CT with contrast / OR

— Months post-RYGB, intermittent severe periumbilical pain, normal CT → internal hernia; diagnostic laparoscopy

— Persistent vomiting post-sleeve, confusion, ataxia → Wernicke; IV thiamine before dextrose

— 2 hrs after meal post-RYGB, sweating, palpitations, glucose 50 → late dumping/post-bariatric hypoglycemia; small frequent low-GI meals, acarbose

— Central obesity, striae, hypokalemia, hypertension → Cushing workup (late-night salivary cortisol, dexamethasone suppression)

— Bradycardia, fatigue, weight gain → TSH

— Hirsutism, oligomenorrhea, BMI 32 → PCOS workup

— Schizophrenia on olanzapine with significant gain → switch to aripiprazole with psychiatry

— T2DM on glipizide and insulin gaining weight → switch to metformin + GLP-1 RA / SGLT2i

— Hypertension on atenolol with gain → switch to ACEi/ARB or carvedilol

— GLP-1 RA in MEN2 / MTC → contraindicated

— Phentermine/topiramate in pregnancy → contraindicated (cleft palate)

— Naltrexone/bupropion in patient on chronic opioids → contraindicated (withdrawal)

Key distinction: Step 3 stems emphasize chronic management decisions (which drug, when to refer, what to monitor next) rather than diagnosis — anchor on the patient's comorbidity profile to pick the right anti-obesity agent.

Stem pattern 1 — "When to start a drug":

Stem pattern 2 — "Best drug for this patient":

Stem pattern 3 — "When to refer to surgery":

Stem pattern 4 — "Post-op complication":

Stem pattern 5 — "Workup before labeling primary obesity":

Stem pattern 6 — "Drug to discontinue / switch":

Stem pattern 7 — "Contraindication recognition":

One-Line Recap

Obesity is a chronic disease: layer intensive lifestyle therapy under pharmacotherapy at BMI ≥30 (or ≥27 with comorbidity) and refer for metabolic surgery at BMI ≥35 (or ≥30 with metabolic disease), choosing the agent and procedure that match the patient's comorbidities and continuing treatment lifelong.

— Pharmacotherapy: BMI ≥30, or ≥27 + weight-related comorbidity

— Surgery (ASMBS 2022): BMI ≥35 (any), or ≥30 + metabolic disease; Asian thresholds lower

— Goal: ≥5% loss in 3–6 months; intensify if not achieved

— ASCVD without diabetes → semaglutide 2.4 mg (SELECT)

— T2DM + obesity → tirzepatide or semaglutide; surgery if uncontrolled

— Migraines/seizures → phentermine/topiramate (avoid in pregnancy — cleft palate)

— Tobacco/depression → naltrexone/bupropion (avoid with opioids, seizures)

— Contraindications matter: MTC/MEN2 excludes GLP-1 RA; pregnancy excludes all anti-obesity drugs

— Sleeve worsens GERD; RYGB treats it and gives best T2DM remission

— Tachycardia >120 post-op → leak until proven otherwise (CCS pearl)

— NSAIDs lifelong contraindicated after RYGB (marginal ulcer)

— Thiamine before glucose in any vomiting post-bariatric patient

— Avoid pregnancy 12–18 months post-op; switch off oral contraceptives after malabsorptive surgery

— Obesity is chronic — stopping pharmacotherapy or skipping bariatric follow-up causes regain

— Lifelong supplementation, multidisciplinary follow-up, mental health screening, cancer screening

— Use person-first language, sized equipment, and address weight bias to improve outcomes

Board pearl: When in doubt on Step 3, ask: "What is this patient's dominant comorbidity?" — that single answer picks the right anti-obesity drug, the right surgical procedure, and the right monitoring plan.

Treatment thresholds:

Drug-of-choice rapid recall:

Bariatric must-knows:

Longitudinal care: