Is Amaryl (glimepiride) a Sodium-Glucose Linked Transporter (SGLT) inhibitor?

Is Amaryl an SGLT Inhibitor?

No, Amaryl (glimepiride) is not an SGLT inhibitor—it is a third-generation sulfonylurea that works by stimulating insulin release from pancreatic beta cells, not by blocking glucose reabsorption in the kidneys. 1, 2

Mechanism of Action: Sulfonylurea, Not SGLT Inhibitor

• Glimepiride stimulates insulin secretion from functional pancreatic beta cells in response to glucose by binding to sulfonylurea receptors on beta cells 1, 3
• This mechanism is fundamentally different from SGLT2 inhibitors (like dapagliflozin, empagliflozin, and canagliflozin), which block sodium-glucose cotransporter 2 in the proximal renal tubule to increase urinary glucose excretion 4, 5
• Glimepiride may also have extrapancreatic mechanisms of action, but these do not involve SGLT inhibition 1

Clinical Distinction from SGLT2 Inhibitors

Glimepiride (Amaryl) Characteristics:

• Dosing: 1-8 mg once daily, with greatest glucose-lowering effects in the first 4 hours after dosing 1, 2
• Hypoglycemia risk: Occurs in 10-20% of patients on monotherapy and ≥50% when combined with insulin, though lower risk than older sulfonylureas like glyburide 1, 6
• Weight effect: Neutral to slight weight gain 7
• Cardiovascular effects: The CAROLINA trial showed glimepiride had similar cardiovascular safety to DPP-4 inhibitors, with no increased MACE risk 4

SGLT2 Inhibitors Characteristics:

• Mechanism: Block renal glucose reabsorption, promoting glucosuria 4, 5
• Hypoglycemia risk: Very low when used alone 4
• Weight effect: Reduce body weight by 1.5-3.5 kg 4
• Cardiovascular/renal benefits: Reduce major cardiovascular events, heart failure hospitalizations, and CKD progression 4

Common Pitfall to Avoid

• Do not confuse drug classes based on glucose-lowering effects alone—while both glimepiride and SGLT2 inhibitors lower HbA1c by approximately 0.5-1.0%, their mechanisms, side effect profiles, and cardiovascular/renal outcomes differ dramatically 4, 1, 2
• Glimepiride requires functional pancreatic beta cells to work, while SGLT2 inhibitors work independently of insulin secretion 1, 5

When Each Drug Class Is Preferred

Use Glimepiride when:

• Cost is a major barrier (glimepiride is inexpensive) 4
• Patient has no established cardiovascular disease, heart failure, or CKD 4
• Rapid glucose lowering is needed in the first weeks of treatment 1, 2

Use SGLT2 Inhibitors when:

• Patient has heart failure (HFrEF or HFpEF) to prevent hospitalizations 4
• Patient has CKD with eGFR 20-60 mL/min/1.73 m² and/or albuminuria to slow progression 4
• Patient has established atherosclerotic cardiovascular disease to reduce MACE 4
• Weight loss is a treatment goal 4