A 30-year-old obese female presents with new-onset headaches, ringing in her ears, and blurry vision. Ibuprofen and avoidance of light has not relieved her symptoms. She denies a history of recent trauma, fever, chills, and fatigue. Past medical history is significant for type 2 diabetes mellitus managed with metformin. She has had 20/20 vision her whole life and wonders if she might need to get eyeglasses. She has 2 healthy school-age children. Her temperature is 36.8°C (98.2°F), heart rate is 90/min, respiratory rate is 15/min, and blood pressure is 135/80 mm Hg. Physical exam is notable for decreased lateral eye movement, and the funduscopic findings are shown in the picture. Laboratory findings are within normal limits and brain imaging is normal. Lumbar puncture demonstrates an elevated opening pressure and normal CSF composition. Which of the following is a side effect of the medication used to treat this condition?

Decreased white blood cell count

A 57-year-old woman presents to her physician for a checkup. The past medical history is significant for diabetes mellitus type 2, and a history of myocardial infarction. The current medications are aspirin, lisinopril, metoprolol, atorvastatin, and metformin. The patient’s HbA1c is 7.9%, and her fasting blood glucose is 8.9 mmol/L (160 mg/dL). Which of the following statements regarding the use of exenatide in this patient is most correct?

It is associated with weight loss in most patients

It cannot be used in combination with metformin

It requires daily subcutaneous injection

It has a high risk of causing severe hypoglycemia when used alone

It is contraindicated in patients with a history of myocardial infarction

A 40-year-old woman with a recent history of carcinoma of the breast status post mastectomy and adjuvant chemotherapy one week ago presents for follow-up. She reports adequate pain control managed with the analgesic drug she was prescribed. Past medical history is significant for hepatitis C and major depressive disorder. The patient denies any history of smoking or alcohol use but says she is currently using intravenous heroin and has been for the past 10 years. However, she reports that she has been using much less heroin since she started taking the pain medication, which is confirmed by the toxicology screen. Which of the following is the primary mechanism of action of the analgesic drug she was most likely prescribed?

Pure agonist at the µ-opioid receptor

Pure antagonist at opioid receptors

Inhibits prostaglandin synthesis

Mixed agonist-antagonist at opioid receptors

Central action via blockade of serotonin reuptake

A 52-year-old man presents to his primary care physician complaining of a blistering rash in his inguinal region. Upon further questioning, he also endorses an unintended weight loss, diarrhea, polydipsia, and polyuria. A fingerstick glucose test shows elevated glucose even though this patient has no previous history of diabetes. After referral to an endocrinologist, the patient is found to have elevated serum glucagon and is diagnosed with glucagonoma. Which of the following is a function of glucagon?

Decreased ketone body production

A 43-year-old male with a history of thyroid cancer status post total thyroidectomy presents to his primary care physician after repeated bouts of headaches. His headaches are preceded by periods of anxiety, palpitations, and sweating. The patient says he is unable to pinpoint any precipitating factors and instead says the events occur without warning. Of note, the patient's father and uncle also have a history of thyroid cancer. On exam his vitals are: T 36.8 HR 87, BP 135/93, RR 14, and O2 Sat 100% on room air. The patient's TSH is within normal limits, and he reports taking his levothyroxine as prescribed. What is the next best step in diagnosing this patient's chief complaint?

Plasma fractionated metanephrines

Abdominal CT scan with and without IV contrast

High dose dexamethasone suppression test

GLP-1 receptor agonists — USMLE Lesson

Mechanism of Action - The Incretin Effect

Incretin Effect: Oral glucose intake stimulates a significantly greater insulin release compared to IV glucose. This effect is driven by gut-derived hormones, primarily Glucagon-Like Peptide-1 (GLP-1).
GLP-1 is released from L-cells in the ileum and colon following a meal and has a very short half-life, as it's rapidly inactivated by the enzyme Dipeptidyl Peptidase-4 (DPP-4).

Primary Actions:

↑ Glucose-dependent insulin secretion.
↓ Glucagon secretion from pancreatic α-cells.
Slows gastric emptying.
Promotes satiety via CNS effects.

⭐ The key advantage is its glucose-dependent mechanism, which significantly lowers the risk of hypoglycemia compared to insulin secretagogues like sulfonylureas.

Glucose metabolism and incretin effect

Pharmacokinetics - Meet the '-tide' Family

GLP-1 agonists are peptides, hence their administration is typically via subcutaneous injection. An oral formulation of semaglutide is a notable exception.
Their half-lives are engineered to vary significantly, which dictates their dosing schedules from twice-daily to once-weekly, improving patient adherence.

Drug	Dosing Frequency	Key Features & Notes
Exenatide	Twice Daily	Shortest acting; derived from Gila monster saliva. Higher risk of antibody formation.
Liraglutide	Daily	Associated with proven cardiovascular benefit (LEADER trial).
Dulaglutide	Weekly	A long-acting formulation, convenient for patients.
Semaglutide	Weekly	Also has proven CV benefit (SUSTAIN-6); available as an oral preparation.
Tirzepatide	Weekly	A newer agent; a dual GIP and GLP-1 receptor agonist showing robust efficacy.

Clinical Use & Benefits - Sweet Perks

Primary Use: Monotherapy or adjunct in Type 2 Diabetes Mellitus.
Glycemic Control: Effectively lowers HbA1c by 1-2%.
- Low risk of hypoglycemia due to glucose-dependent action.
Weight Management: Promotes significant weight loss.
Cardiovascular & Renal Protection: Reduces risk of major adverse cardiovascular events (MACE) and slows diabetic nephropathy progression.

⭐ Liraglutide, semaglutide, and dulaglutide have established cardiovascular benefits, making them a preferred choice in T2DM patients with coexisting atherosclerotic cardiovascular disease.

Adverse Effects & Contraindications - Guts & Glands

Gastrointestinal (Most Common): Nausea, vomiting, diarrhea, and constipation are frequent.
- Slow dose titration is key to improving tolerability.
Pancreatitis: ↑ risk of acute pancreatitis. ⚠️
Gallbladder: ↑ risk of cholelithiasis and cholecystitis.
Injection Site Reactions: Can cause local erythema and nodules.

⭐ Black Box Warning: Contraindicated with a personal or family history of Medullary Thyroid Carcinoma (MTC) or Multiple Endocrine Neoplasia type 2 (MEN 2).

High‑Yield Points - ⚡ Biggest Takeaways

GLP-1 agonists (-tide suffix; e.g., exenatide, liraglutide) are incretin mimetics that also suppress glucagon secretion.

They stimulate glucose-dependent insulin release, leading to a very low risk of hypoglycemia.

Major benefits beyond glycemic control are significant weight loss and cardioprotective effects.

Primary side effects are gastrointestinal (nausea, vomiting, diarrhea) and delayed gastric emptying.

Associated with an increased risk of acute pancreatitis.

Contraindicated in patients with a personal or family history of medullary thyroid carcinoma or MEN2.

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