Empagliflozin/Linagliptin as Add-On to Metformin Therapy in Type 2 Diabetes

ADA Diabetes Care Journal:

Metformin is the recommended first-line pharmacotherapy for patients with type 2 diabetes, but most patients will ultimately require additional therapies to maintain glycemic control.

Maintaining intensive glucose control early in the disease process may lead to legacy benefits that persist beyond the period of treatment.

Therefore, when metformin fails to achieve glycemic control, add-on combination therapy with two oral antidiabetes agents may be beneficial.


The authors of this study evaluated the efficacy and safety of combinations of empagliflozin and linagliptin in lowering HbA1c levels in patients with type 2 diabetes with inadequate response to metformin.

Reductions in HbA1c at week 24 with combined empagliflozin and linagliptin added to metformin were superior to those with empagliflozin or linagliptin alone.

Efficacy of treatment was maintained during the 52-week study, and the proportion of adverse events was similar across treatment arms.

In conclusion, in patients with type 2 diabetes, combined empagliflozin/linagliptin as add-on to metformin provided greater glucose-lowering efficacy and significantly reduced HbA1c than the individual components, with a low risk of hypoglycemia. Empagliflozin/linagliptin was well tolerated, with safety profiles similar to the known safety profiles of empagliflozin and linagliptin.

These results suggest that immediate use of triple therapy in patients who have failed on metformin may provide advantages over the traditional staggered treatment approach.

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To evaluate the efficacy and safety of combinations of empagliflozin/linagliptin as second-line therapy in subjects with type 2 diabetes inadequately controlled on metformin.


Subjects were randomized to a combination of empagliflozin 25 mg/linagliptin 5 mg (n = 137), empagliflozin 10 mg/linagliptin 5 mg (n = 136), empagliflozin 25 mg (n = 141), empagliflozin 10 mg (n = 140), or linagliptin 5 mg (n = 132) as add-on to metformin for 52 weeks. The primary end point was change from baseline in HbA1c at week 24.


At week 24, reductions in HbA1c (mean baseline 7.90-8.02% [62.8-64.1 mmol/mol]) with empagliflozin/linagliptin were superior to those with empagliflozin or linagliptin alone as add-on to metformin. In these groups, respectively, 61.8, 57.8, 32.6, 28.0, and 36.1% of subjects with baseline HbA1c ≥7% (≥53 mmol/mol) had HbA1c <7% (<53 mmol/mol) at week 24. Efficacy was maintained at week 52. The proportion of subjects with adverse events (AEs) over 52 weeks was similar across treatment arms (68.6-73.0%), with no hypoglycemic AEs requiring assistance.


Combinations of empagliflozin/linagliptin as second-line therapy for 52 weeks significantly reduced HbA1c compared with the individual components and were well tolerated.

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This is for informational purposes only. You should consult your clinical textbook for advising your patients.