Does Vildagliptin Cause Glucosuria?
No, vildagliptin (a DPP-4 inhibitor) does not cause glucosuria—this is a mechanism specific to SGLT2 inhibitors, not DPP-4 inhibitors.
Mechanism of Action: Why Vildagliptin Does NOT Cause Glucosuria
Vildagliptin works by inhibiting the DPP-4 enzyme, which prevents the degradation of incretin hormones (GLP-1 and GIP), thereby enhancing insulin secretion and inhibiting glucagon secretion in a glucose-dependent manner 1, 2.
The drug increases endogenous GLP-1 levels by reducing its deactivation, which stimulates insulin secretion from pancreatic beta cells and suppresses glucagon release from alpha cells 3, 4.
Vildagliptin reduces blood glucose primarily through three mechanisms: enhanced insulin secretion, suppressed glucagon secretion, and reduced hepatic glucose production—none of which involve renal glucose excretion 4, 2.
The Class That DOES Cause Glucosuria: SGLT2 Inhibitors
SGLT2 inhibitors (dapagliflozin, empagliflozin, canagliflozin) are the drug class that causes glucosuria, as they work by inhibiting renal tubular SGLT2 responsible for glucose reabsorption from urine, reducing the renal glucose threshold and promoting urinary glucose excretion 1.
This is a completely different mechanism from DPP-4 inhibitors like vildagliptin, which work through incretin enhancement rather than renal glucose excretion 1.
Clinical Implications and Common Pitfalls
Do not confuse DPP-4 inhibitors with SGLT2 inhibitors—they are distinct drug classes with entirely different mechanisms of action 1, 3.
Vildagliptin's main side effects are NOT related to glucosuria but rather include potential gastrointestinal complaints, and when combined with sulfonylureas, an increased risk of hypoglycemia 3, 5.
The glucose-lowering effect of vildagliptin is modest (HbA1c reduction of 0.4-0.9%), with a low risk of hypoglycemia when used alone and weight-neutral effects 1, 3.
Vildagliptin requires dose adjustment in moderate-to-severe renal impairment, unlike linagliptin which requires no dose adjustment regardless of renal function 1, 3.