Linagliptin and Empagliflozin Combination Therapy for Type 2 Diabetes
For patients with type 2 diabetes, the fixed-dose combination of empagliflozin and linagliptin (Glyxambi) is recommended as an effective treatment option, particularly for patients with established cardiovascular disease or high cardiovascular risk, due to empagliflozin's proven cardiovascular mortality benefits and renal protective effects. 1
Mechanism of Action and Efficacy
The combination of empagliflozin (SGLT2 inhibitor) and linagliptin (DPP-4 inhibitor) provides complementary mechanisms of action:
- Empagliflozin: Reduces glucose reabsorption in the kidneys, leading to increased urinary glucose excretion 2
- Linagliptin: Increases incretin hormones that stimulate insulin secretion and decrease glucagon levels 3
Clinical studies have demonstrated that this combination:
- Provides significant HbA1c reduction (0.6-1.2% greater than individual components) 4, 5
- Offers weight loss benefits compared to linagliptin alone 4
- Has low risk of hypoglycemia 4, 6
Patient Selection and Indications
The empagliflozin/linagliptin combination is particularly beneficial for:
Patients with established cardiovascular disease or high CV risk: Empagliflozin reduces cardiovascular mortality by 38% and hospitalization for heart failure by 35% 1
Patients with chronic kidney disease: Empagliflozin reduces progression of diabetic kidney disease 1, 7
Patients with inadequate glycemic control on metformin: As a second-line therapy when both medications are appropriate 7
Patients with obesity: The combination provides weight loss benefits 5
Dosing and Administration
The fixed-dose combination (Glyxambi) is available as:
- 10 mg empagliflozin/5 mg linagliptin
- 25 mg empagliflozin/5 mg linagliptin
Administered as a once-daily oral tablet, which may improve medication adherence compared to taking multiple pills 8, 9.
Cardiovascular and Renal Benefits
The combination therapy offers significant advantages beyond glycemic control:
Cardiovascular protection: Empagliflozin demonstrated a 14% reduction in the composite outcome of MI, stroke, and cardiovascular death (HR 0.86; 95% CI 0.74-0.99) 1
Heart failure reduction: Empagliflozin reduces hospitalization for heart failure, making it particularly valuable for patients with or at risk for heart failure 7, 1
Renal protection: Empagliflozin slows progression of diabetic kidney disease 1
Safety Considerations
Key safety considerations include:
Low hypoglycemia risk: The combination has a low risk of hypoglycemia compared to sulfonylureas 4, 6
Urinary tract infections: Monitor for UTIs, particularly mycotic infections with empagliflozin 7
Euglycemic diabetic ketoacidosis: Rare but serious risk with SGLT2 inhibitors, particularly in patients with poor food intake 7
Blood pressure effects: The combination may reduce blood pressure, requiring monitoring in patients prone to hypotension 8
Place in Therapy Algorithm
First-line: Metformin remains first-line therapy for most patients with type 2 diabetes 7
Second-line options:
- For patients with established cardiovascular disease or high CV risk: Empagliflozin/linagliptin is recommended 1
- For patients with BMI >35 kg/m²: GLP-1 RAs may be preferred, though empagliflozin/linagliptin is an acceptable option 7
- For patients with BMI <30 kg/m²: DPP-4 inhibitors and SGLT2 inhibitors are equally preferable options 7
Third-line therapy: When dual therapy is insufficient, combination therapy with empagliflozin/linagliptin plus metformin may be considered 7
Conclusion
The fixed-dose combination of empagliflozin and linagliptin offers a convenient, effective treatment option with complementary mechanisms of action for patients with type 2 diabetes. Its cardiovascular and renal benefits make it particularly valuable for patients with established cardiovascular disease or high cardiovascular risk.