Clinical Utility of the Dipeptidyl Peptidase-4 Inhibitor Linagliptin

Abstract

Linagliptin is a xanthine-based, oral DPP-4 inhibitor that has been approved in the United States and Europe. It has been evaluated extensively in clinical trials, and results in improved glycemic control when used as monotherapy, initial combination therapy with metformin or pioglitazone, add-on therapy to metformin and/or a sulfonylurea, or add-on therapy to basal insulin (with or without oral antidiabetic drugs). Consistent with other members of its class, the benefits of linagliptin also include a low risk of hypoglycemia and weight gain. However, linagliptin is the first DPP-4 inhibitor to be approved as a once-daily, 5-mg dose and, due to its primarily non-renal route of excretion, no dosage adjustment is required for patients with renal or hepatic impairment. The pharmacokinetics and pharmacodynamics of linagliptin are not affected to a clinically meaningful degree by race or ethnicity and linagliptin has very low potential for drug-drug interactions.

Linagliptin improved glycaemic control without weight gain or hypoglycaemia in patients with Type 2 diabetes inadequately controlled by a combination of metformin and pioglitazone: a 24‐week randomized, double‐blind study

“…Because of the progressive decline of b-cell function in Type 2 diabetes, most patients eventually require intensification of anti-diabetes therapy to maintain glycaemic control [1]. Given the complementary mechanisms of action of linagliptin, metformin and pioglitazone, triple combination therapy with these oral anti-hyperglycaemic drugs is theoretically an attractive treatment strategy [7,[23][24][25]. These results support the use of this combination as an effective third-line therapeutic option when dual therapy with metformin and pioglitazone fails.…”

“…The addition of a dipeptidyl peptidase‐4 (DPP‐4) inhibitor to this combination is an attractive treatment option, offering an additional complementary mechanism of action. DPP‐4 inhibitors increase active levels of glucagon‐like peptide 1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide, increasing insulin secretion and inhibiting glucagon secretion . The increase in GLP‐1 may also improve β‐cell function .…”

Single-pill combination therapy for type 2 diabetes mellitus: linagliptin plus empagliflozin

“…The Phase 3 program also demonstrated that linagliptin treatment was weight neutral and that the rate of serious adverse events (AEs) across all trials was low 17,18 . The risk of hypoglycemia with linagliptin is low, except when used in combination with a sulfonylurea or insulin 17,18,25 .…”

“…The risk of hypoglycemia with linagliptin is low, except when used in combination with a sulfonylurea or insulin 17,18,25 .…”

Linagliptin in Combination With Metformin Ameliorates Diabetic Osteoporosis Through Modulating BMP-2 and Sclerostin in the High-Fat Diet Fed C57BL/6 Mice

“…Metformin reduces fracture risk and protects bone health as per several clinical, preclinical, and in-vitro studies (41)(42)(43)(44)(45)(46)(47)(48). Currently, linagliptin is clinically prescribed either as a monotherapy in metformin intolerant patients or as a combination with metformin for better glycemic control (35,49,50). However, the role of the combination of linagliptin and metformin in type 2 diabetesassociated osteoporosis has not been investigated yet.…”