Quiz 10: Biomedical Sciences/Pharmacotherapy (Funk)

What is the definition of a "syndrome"?

a group of signs and symptoms that occur together and characterize a particular condition; they occur together more frequently than expected by chance alone

What is the consensus diagnostic definition of metabolic syndrome?

Diagnosed when a patient has 3 out of 5 risk factors:

1. elevated waist circumference (>40" men, >35" women)

2. elevated triglycerides (≥150 mg/dL or on treatment)

3. reduced HDL (<40 mg/dL men, <50 mg/dL women or on treatment)

4. elevated BP ≥130/85 mmHg or on treatment

5. elevated fasting glucose ≥100 mg/dL or on treatment

How does drug therapy affect the diagnosis of metabolic syndrome risk factors?

If a patient is on drug therapy for triglycerides, HDL, blood pressure, or fasting glucose, they are considered to have that risk factor, even if their lab/clinical values are normalized

What proportion of the U.S. population has metabolic syndrome?

~35% of U.S. adults

Why is metabolic syndrome considered a major public health issue?

because of increasing sedentary behavior and obesity in the population

Why is metabolic syndrome considered a clinical problem?

individuals with metabolic syndrome must be identified and treated for modifiable cardiometabolic risk factors

How does metabolic syndrome affect future cardiovascular risk?

patients with metabolic syndrome have 2× the risk of developing cardiovascular disease within 5-10 years

How does metabolic syndrome affect diabetes risk?

patients have 5× the risk of developing type 2 diabetes

What is currently unknown about the risk relationship between metabolic syndrome components?

it is unclear whether risks are additive (sum of individual risks) or whether components interact to create a greater-than-additive risk

What are the major causes of metabolic syndrome?

overweight/obesity, sedentary lifestyle, and genetics

secondary factors include aging, pro-inflammatory states, and hormonal changes

What dietary patterns reduce metabolic syndrome risk?

DASH diet and Mediterranean diet, emphasizing fruits, vegetables, legumes, whole grains, and limiting added sugar and salt

What is the recommended physical activity level for metabolic syndrome prevention?

At least 150 minutes/week of moderate-intensity aerobic activity (consistent across ADA, AHA, CDC)

What BMI range is generally considered an appropriate weight?

BMI of 18.5-24.9 kg/m²

What is the clinical relevance of metabolic syndrome in treatment guidelines?

In the 2018 cholesterol guidelines, metabolic syndrome is a risk-enhancing factor supporting statin therapy in non-diabetic adults

Why is it still important to understand metabolic syndrome despite debates about its significance?

because the term is still widely used, it helps identify high-risk patients, and clinicians must know how to treat each component (BP, glucose, lipids, waist circumference)

What GLP-1 medications are FDA-approved for weight management?

Semaglutide (Wegovy) and tirzepatide (Zepbound).

Liraglutide (Saxenda) exists but is rarely used due to once-daily dosing and lower efficacy

What BMI criteria qualify a patient for GLP-1 therapy for weight loss?

BMI ≥ 30, or BMI ≥ 27 with at least one weight-related comorbidity (HTN, T2DM, dyslipidemia, OSA, CVD)

What is the major contraindication for GLP-1 weight-loss therapy?

Personal or family history of MTC or MEN2. Based on animal data only; not shown in humans

What key warnings exist for GLP-1 medications?

severe GI disease, acute kidney injury (from dehydration), pancreatitis (uncertain), gallbladder disease, hypoglycemia when combined with insulin/SU, pregnancy (stop 2 months prior)

What major cardiovascular outcome was shown in the SELECT trial?

semaglutide reduced 3-point MACE (nonfatal MI, nonfatal stroke, CV death) in adults with BMI ≥27 and established CVD but no diabetes

Which patients qualify for GLP-1 coverage under SELECT-based insurance criteria?

those with prior MI, prior stroke, or symptomatic PAD, not simply "risk factors"

What new indication was approved for tirzepatide (Zepbound)?

treatment of obstructive sleep apnea (OSA) in adults with obesity, based on SURMOUNT-OSA

What was the key SURMOUNT-OSA outcome?

tirzepatide reduced apnea-hypopnea index (AHI) by ~50%, a clinically meaningful improvement

What inclusion criterion is often required for Zepbound OSA coverage?

documented moderate-severe OSA (AHI ≥15), usually by a sleep-medicine provider or sleep study

What is the comparative weight-loss efficacy of tirzepatide vs semaglutide?

tirzepatide ≈ 20% weight loss; semaglutide ≈ 13%

Both significantly outperform older agents (~8-10%)

What are the most common GLP-1 adverse effects?

Nausea, vomiting, diarrhea, constipation, delayed gastric emptying, retained gastric contents.

GI side effects are dose-dependent and common

What causes the constipation experienced with GLP-1 therapy?

slowed gastric and intestinal motility → slower transit → constipation. Part of the intended mechanism

How is GLP-1-associated nausea best managed non-pharmacologically?

small meals, avoid high-fat/spicy foods, eat slowly, stop at first fullness, separate fluids from meals, avoid carbonation, maintain hydration

How can GLP-1-induced constipation be managed?

hydration, fiber, physical activity; consider fiber supplement or stool softener if needed

Why can GLP-1 therapy cause acute kidney injury?

significant vomiting/diarrhea → volume depletion → prerenal AKI risk

What evidence exists regarding pancreatitis risk with GLP-1s?

data is inconsistent; risk appears low or doubtful, but still monitored

Why do patients regain weight after stopping GLP-1 therapy?

return of hunger signaling ("food noise"), metabolic adaptation, and loss of the drug's appetite-suppressing effects → substantial rebound weight gain (14% regain seen in trials)

How can lean-mass loss and rebound weight gain be mitigated during GLP-1 therapy?

resistance exercise 2-3×/week and adequate protein intake (0.8-1.5 g/kg/day) preserve lean mass and reduce rebound regain

What administration counseling should patients receive for GLP-1 injections?

weekly subcutaneous injections; preloaded needles; press-and-hold until the indicator completes; rotate sites; injection is generally easy and low-pain

Which medications are FDA-approved for chronic weight management?

Orlistat, phentermine/topiramate (Qsymia), naltrexone/bupropion (Contrave), liraglutide, semaglutide (Wegovy), tirzepatide (Zepbound)

What are the shared FDA indications for all chronic obesity medications?

BMI ≥30 OR BMI ≥27 with ≥1 weight-related comorbidity (DM, HTN, dyslipidemia), always in combination with a reduced-calorie diet

What is the universal contraindication?

Pregnancy. Weight gain is physiologically expected, and safety data are lacking

What do guidelines state about using medications for chronic obesity?

pharmacotherapy should be an adjunct to behavioral modification, especially after inadequate response to lifestyle interventions per ES and AGA

Why are obesity medications recommended despite stigma?

hese medications ameliorate comorbidities and improve adherence to lifestyle changes; stigma should not prevent evidence-based treatment

What monitoring schedule is recommended for chronic obesity medications?

monthly for 3 months, then every 3 months

- assess efficacy, safety, tolerability

When should a chronic obesity medication be discontinued?

if the patient has <5% weight loss after 12 weeks at maintenance dose or if not tolerated

What universal counseling points apply to all chronic obesity medications?

Use with lifestyle changes; discuss AE; warn that continuation depends on effectiveness at 3-4 months.

This prevents surprise if the drug is later discontinued.

Which chronic obesity medication shows the lowest proportion achieving ≥5% weight loss?

Orlistat (~44%)

Which medication shows the highest proportion achieving ≥5% weight loss?

tirzepatide (~90%), followed by semaglutide (~84%)

Why must caution be used when comparing efficacy across agents?

trials included different patient populations and were not head-to-head; trends are useful but not definitive

What is a distinguishing aspect of Orlistat?

long duration of safety data; works via fat malabsorption causing GI adverse effects; requires multivitamin supplementation

What is a distinguishing aspect of naltrexone/bupropion (Contrave)?

helps with cravings and addictive eating; both drugs have roles in addiction (alcohol, opioids, smoking)

- useful in patients with comorbid depression

What is a distinguishing aspect of phentermine/topiramate (Qsymia)?

Appetite suppression; topiramate also used for migraine prophylaxis

What distinguishing aspects apply to semaglutide and tirzepatide?

once-weekly injections; glycemic control; semaglutide has CV benefit; tirzepatide causes the most weight loss

What are major safety concerns with naltrexone/bupropion?

opioids will not work due to naltrexone; bupropion lowers seizure threshold; avoid in uncontrolled HTN

What are major safety concerns with phentermine/topiramate?

stimulant effects (BP ↑, anxiety, insomnia); topiramate teratogenicity; avoid in patients with CV risks or those planning pregnancy

What are major safety considerations for GLP-1 agents?

injectable route; GI effects; risk for dehydration-related complications; typical GLP-1 warnings apply but specifics not detailed in this deck

According to additional efficacy data, which doses of tirzepatide show greatest weight loss?

tirzepatide 10 mg and 15 mg produce the greatest reductions in percent weight change among listed agents

Why are semaglutide and tirzepatide preferred for most patients?

guidelines state these agents may be prioritized for long-term obesity treatment due to magnitude of net benefit

What are the typical cash costs of obesity medications?

GLP-1 agents cost ~$1300/month

Contrave and Qsymia ~$200-600/month

EM started Wegovy 0.25mg 12 weeks ago and titrated appropriately with no GI issues. What dose should she be on now based on standard titration?

1 mg

3 multiple choice options

EM missed 3 doses of Wegovy while on vacation. She previously tolerated all doses well. What dose should she restart?

Restart 0.5 mg

3 multiple choice options

If EM had missed only ONE dose (1 week instead of 3), what would be the correct restart dose?

Continue 1 mg

3 multiple choice options

EM reports occasional, non-bothersome indigestion. What is the most appropriate action?

Restart as planned

3 multiple choice options

Which counseling point is MOST important when restarting Wegovy after missed doses?

Expect temporary GI side effects

3 multiple choice options

C is experiencing GI side effects on Saxenda 2.4 mg that worsened after dose increase. What information is MOST important to gather?

Exact onset and progression of symptoms

3 multiple choice options

JC tolerated 1.8 mg Saxenda but not 2.4 mg. What starting Zepbound dose is appropriate?

2.5 mg weekly

3 multiple choice options

When should JC start Zepbound after stopping Saxenda if he currently has active GI symptoms?

After symptoms resolve

3 multiple choice options

Which explanation BEST describes why Zepbound may cause more weight loss than liraglutide?

It activates GLP-1 and GIP receptors

3 multiple choice options

When switching from Saxenda to a weekly agent like Zepbound, when should the first dose ideally be given (if no GI symptoms)?

On the next scheduled injection day

3 multiple choice options

AW completed 4 doses of Wegovy 1.7 mg and is due for 2.4 mg, but Wegovy is on backorder. What Zepbound dose is most appropriate?

5 mg

3 multiple choice options

When should AW take her first Zepbound dose?

7 days after last Wegovy dose

3 multiple choice options

AW tolerated Wegovy well. Why is starting Zepbound at 5 mg reasonable?

Cross-tolerance minimizes GI risk

3 multiple choice options

If AW had significant GI symptoms on Wegovy 1.7 mg, what Zepbound dose would be preferred?

2.5 mg

3 multiple choice options

A patient switching from Wegovy to Zepbound should primarily be counseled that:

GI symptoms can return

3 multiple choice options

AL has persistent nausea after Trulicity 3 mg injections. Which nonpharm strategy is MOST supported?

Smaller, more frequent meals

3 multiple choice options

Which meal pattern reduces GLP-1-related nausea?

Avoiding fluids with meals

3 multiple choice options

Trulicity is no longer covered. Her A1c is 5.0% and she wants continued weight loss. What starting Ozempic dose is appropriate?

0.5 mg

3 multiple choice options

It follow-up, AL has no weight loss on 0.5 mg Ozempic and minimal nausea. What is the next best step?

Increase to 1 mg

3 multiple choice options

If AL reported worsening nausea at follow-up, what is the preferred next step?

Hold dose or decrease

3 multiple choice options

JH wants the most effective weight-loss medication. Which is best based on evidence?

Tirzepatide 15 mg

3 multiple choice options

What starting dose of tirzepatide is correct for JH?

2.5 mg

3 multiple choice options

After 3 weeks on tirzepatide 2.5 mg, JH wants to stop injections and switch to sublingual semaglutide. What is the correct first step?

Start sublingual semaglutide 1 mg daily

3 multiple choice options

When should she start sublingual semaglutide after her last tirzepatide dose?

7 days later

3 multiple choice options

What is an appropriate counseling point when switching from injectable tirzepatide to sublingual semaglutide?

Expect possible reduced potency vs injectables

2 multiple choice options