Question-

A 42-year-old woman presents to the clinic with complaints of increased thirst, frequent urination, and recent unexplained weight loss. She has no significant past medical history, but her father was diagnosed with type 2 diabetes mellitus in his 50s. Her fasting blood glucose level is 156 mg/dL, and a repeat measurement confirms the diagnosis of diabetes mellitus. You start her on metformin and recommend lifestyle changes. Six months later, she returns to the clinic with persistent hyperglycemia despite compliance with her medication and diet. Her HbA1c is 9.2%. Examination reveals a BMI of 25 kg/m². You decide to add a second agent to improve glycemic control.

Which of the following medications would be most appropriate to add at this stage, given her clinical profile?

A) Pioglitazone
B) Insulin glargine
C) Liraglutide
D) Acarbose
E) Sitagliptin

Correct Answer: C) Liraglutide

Genetic Predisposition + Environmental Factors
🧠 Family history of diabetes → ↑ Risk of insulin resistance (muscle, fat, liver)

⬇️

Insulin Resistance (Peripheral Tissues)
🧠 Muscle, fat: ↓ Glucose uptake
🧠 Liver: ↑ Glucose production (gluconeogenesis)
⬇️

Effect: Hyperglycemia (↑ Blood glucose)

⬇️

Compensatory Hyperinsulinemia
🧠 Early stage: Pancreas ↑ insulin production to counter hyperglycemia
🧠 Temporary normoglycemia

⬇️

Progressive β-cell Dysfunction
🧠 Pancreas: β-cells overworked → Progressive ↓ insulin production

⬇️

Persistent Hyperglycemia
🧠 HbA1c ↑ (above 6.5%), Fasting glucose > 126 mg/dL
🧠 Polyuria (due to osmotic diuresis)
🧠 Polydipsia (due to dehydration from frequent urination)
🧠 Weight loss (glucose loss, energy deficiency)

⬇️

Therapeutic Options

1. Liraglutide (GLP-1 agonist) 🧠
Correct answer
• Mechanism: ↑ Insulin secretion, ↓ Glucagon → ⬇️ Blood glucose
• Key Insight 🧠: Promotes weight loss
• Best choice for this patient (BMI = 25, weight loss) due to dual action on glucose and weight control

⬇️

2. Pioglitazone (Thiazolidinedione)
• Mechanism: ↑ Insulin sensitivity in peripheral tissues
• Effect: ⬇️ Blood glucose
• Key Insight 🧠: Causes weight gain → Incorrect for this patient (normal BMI, weight loss)

⬇️

3. Insulin glargine (Long-acting insulin)
• Mechanism: Direct insulin replacement
• Effect: ⬇️ Blood glucose
• Key Insight 🧠: Often reserved for more advanced disease → Incorrect at this stage, patient is not insulin-dependent yet

⬇️

4. Acarbose (α-glucosidase inhibitor)
• Mechanism: Slows carbohydrate absorption in intestines
• Effect: Mild ⬇️ Blood glucose
• Key Insight 🧠: Less potent, HbA1c reduction is minimal → Not effective enough here

⬇️

5. Sitagliptin (DPP-4 inhibitor)
• Mechanism: ↑ GLP-1 levels → Moderate ⬇️ Blood glucose
• Key Insight 🧠: Lacks weight loss benefit compared to GLP-1 agonists → Incorrect for patient needing both glucose and weight control

Flashcards

Stay Hungry, Stay Curious!

Your Brother In This Struggle

Dr. Shoaib Ahmad