Which of these drugs will cause glycosuria without hyperglycemia: Angiotensin-Converting Enzyme Inhibitors (ACEI), Calcium Channel Blockers (CCB), Diuretics, or Sympathomimetic agents?

Which Drug Causes Glycosuria Without Hyperglycemia?

SGLT2 inhibitors are the only drugs among the options that cause glycosuria without hyperglycemia, but they are not listed among the choices (ACEI, CCB, Diuretics, or Sympathomimetics). Among the given options, none typically cause glycosuria without hyperglycemia as their primary mechanism of action.

Analysis of Each Drug Class

Diuretics

• Thiazide and loop diuretics can cause hyperglycemia through multiple mechanisms:
  • Inhibition of glycolytic enzymes (hexokinase, phosphofructokinase, pyruvate kinase) 1
  • Decreased insulin sensitivity 2
  • Hypokalemia-induced impairment of insulin secretion
  • In ALLHAT, diabetes incidence after 4 years was 11.8% with chlorthalidone therapy 3
• Diuretics do not directly cause glycosuria without hyperglycemia

ACE Inhibitors (ACEI)

• ACEIs have neutral or beneficial effects on glucose metabolism
• They are often preferred in diabetic patients due to their renoprotective effects 3
• ACEIs do not cause glycosuria without hyperglycemia
• They are recommended for hypertensive patients with diabetes or metabolic syndrome due to their favorable metabolic profile 3

Calcium Channel Blockers (CCB)

• CCBs are generally metabolically neutral 3
• They do not directly affect glucose handling in the kidneys
• No evidence suggests they cause glycosuria without hyperglycemia
• Dihydropyridine CCBs are often used in combination with RAS blockers in diabetic patients 3

Sympathomimetics

• Sympathomimetics (beta-agonists, alpha-agonists) typically raise blood glucose through:
  • Increased glycogenolysis
  • Decreased insulin secretion
  • Increased gluconeogenesis
• They do not cause isolated glycosuria without hyperglycemia

Important Clinical Context

For comparison, SGLT2 inhibitors (not listed in the options) are the only major drug class that causes glycosuria without hyperglycemia as their primary mechanism:

• They inhibit sodium-glucose cotransporter 2 in the proximal tubule
• This prevents reabsorption of filtered glucose, causing glycosuria regardless of blood glucose levels 4, 5
• The amount of glycosuria is proportional to GFR and degree of hyperglycemia 4

Clinical Implications

Understanding which medications affect glucose handling is important for:

1. Managing patients with diabetes or prediabetes
2. Interpreting urinalysis results correctly
3. Selecting appropriate antihypertensive therapy in metabolic syndrome or diabetes

Among the options provided (ACEI, CCB, Diuretics, Sympathomimetics), none characteristically cause glycosuria without hyperglycemia as their primary mechanism of action.