What is the recommended dosing of evogliptin for an adult with type 2 diabetes, including adjustments for estimated glomerular filtration rate, hepatic impairment, and elderly patients?

Evogliptin Dosing for Adults with Type 2 Diabetes

Evogliptin 5 mg once daily is the standard dose for adults with type 2 diabetes, regardless of renal function, hepatic impairment, or age, making it the simplest DPP-4 inhibitor to prescribe. 1

Standard Dosing

• Administer evogliptin 5 mg once daily without regard to meals, as this single dose has demonstrated non-inferiority to linagliptin 5 mg in reducing HbA1c by approximately 0.85–0.94% over 12–24 weeks. 1
• The 5 mg dose is the only approved strength; no dose titration is required or recommended. 1

Renal Impairment Adjustments

• No dose adjustment is necessary for any degree of renal impairment, including patients with eGFR < 30 mL/min/1.73 m² or those on dialysis, because evogliptin shares the renal-friendly profile of linagliptin (minimal renal excretion). 2, 3
• This contrasts sharply with other DPP-4 inhibitors: sitagliptin requires reduction to 25 mg daily when eGFR < 30 mL/min/1.73 m², saxagliptin to 2.5 mg daily when eGFR ≤ 45 mL/min/1.73 m², and alogliptin to 6.25 mg daily when eGFR < 30 mL/min/1.73 m². 4, 2
• For patients with eGFR 30–60 mL/min/1.73 m², evogliptin 5 mg daily is preferred over sitagliptin (which requires 50 mg daily) or saxagliptin (which requires 2.5 mg daily) because it eliminates the need for dose calculation and reduces prescribing errors. 4, 2
• For patients with eGFR < 30 mL/min/1.73 m² or on dialysis, evogliptin 5 mg daily is preferred over sitagliptin 25 mg daily because the single-dose simplicity improves adherence and safety. 2, 3

Hepatic Impairment

• No dose adjustment is required for hepatic impairment of any severity, as evogliptin undergoes primarily hepatic metabolism without accumulation of toxic metabolites. 2, 3

Elderly Patients

• No dose adjustment is required based on age alone, even in patients > 65 years, because evogliptin's renal-independent clearance eliminates the age-related decline in kidney function as a dosing concern. 2, 3
• Elderly patients with fluctuating or severe renal impairment benefit from evogliptin's fixed 5 mg dose, which avoids the complexity of frequent dose recalculations required with sitagliptin or saxagliptin. 2, 3

Clinical Positioning and Guideline Context

• Evogliptin is positioned as an alternative DPP-4 inhibitor when SGLT2 inhibitors or GLP-1 receptor agonists cannot be used (e.g., due to contraindications, intolerance, or cost), particularly in patients with eGFR ≥ 30 mL/min/1.73 m². 2
• For patients with established atherosclerotic cardiovascular disease, heart failure, or albuminuric chronic kidney disease (UACR ≥ 200 mg/g), SGLT2 inhibitors or GLP-1 receptor agonists are strongly preferred over evogliptin because of superior mortality and cardiovascular outcome data. 2, 3
• When metformin plus an SGLT2 inhibitor does not achieve glycemic targets, a GLP-1 receptor agonist should be added before considering evogliptin, as GLP-1 agonists provide cardiovascular protection and require no renal dose adjustment. 2

Efficacy and Safety

• Evogliptin reduces HbA1c by approximately 0.4–0.9%, comparable to other DPP-4 inhibitors, with minimal hypoglycemia risk when used as monotherapy. 3, 1
• In the EVERGREEN study, evogliptin reduced mean amplitude of glycemic excursion (MAGE) by 24.6 mg/dL, demonstrating improved glycemic variability without serious adverse events. 1
• At 24 weeks, 80.2% of patients achieved HbA1c < 7.0% on evogliptin 5 mg daily, with a sustained HbA1c reduction of 0.94%. 1
• The most common adverse events are upper respiratory tract infection, headache, and urinary tract infection, occurring at rates comparable to placebo. 5, 1

Cardiovascular Safety

• Like other DPP-4 inhibitors, evogliptin has demonstrated cardiovascular safety but no cardiovascular benefit in outcomes trials, distinguishing it from SGLT2 inhibitors and GLP-1 receptor agonists. 2, 3
• Evogliptin does not increase heart failure hospitalization risk, unlike saxagliptin (27% relative increase) and alogliptin, making it safer in patients with cardiac disease. 3

Combination Therapy

• Evogliptin can be combined with metformin, sulfonylureas, or thiazolidinediones when monotherapy provides inadequate glucose control. 1
• When adding evogliptin to sulfonylurea therapy, reduce the sulfonylurea dose by approximately 50% to prevent hypoglycemia, as the combination increases hypoglycemia risk by approximately 50% compared with sulfonylurea alone. 3
• Do not combine evogliptin with GLP-1 receptor agonists, as the combination provides no additional clinical benefit and is not recommended. 2

Practical Decision Algorithm

1. Assess renal function and albuminuria (eGFR and UACR). 2
2. Prioritize first-line agents: If eGFR ≥ 30 mL/min/1.73 m², start metformin + SGLT2 inhibitor; if further glucose lowering is needed, add GLP-1 receptor agonist. 2
3. Consider evogliptin only when SGLT2 inhibitors and GLP-1 receptor agonists are unsuitable (contraindications, intolerance, or cost). 2, 3
4. Prescribe evogliptin 5 mg once daily regardless of eGFR, hepatic function, or age—no dose adjustment is ever required. 2, 1
5. Monitor HbA1c every 3 months during treatment to determine if additional intensification is needed. 2

Common Pitfalls to Avoid

• Do not use evogliptin as first-line therapy in patients with established atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease with albuminuria—SGLT2 inhibitors or GLP-1 receptor agonists are strongly preferred. 2, 3
• Do not combine evogliptin with other DPP-4 inhibitors (e.g., sitagliptin, linagliptin), as this provides no additional benefit and increases adverse event risk. 2, 3
• Do not delay adding prandial insulin when basal insulin exceeds 0.5 units/kg/day without achieving targets; evogliptin is insufficient for severe hyperglycemia requiring insulin intensification. 6
• Do not prescribe evogliptin in hospitalized patients requiring insulin therapy, as DPP-4 inhibitors are not recommended for routine use in hospital settings. 3