Mechanism of Action

How does Linagliptin work?

Linagliptin is a ‘gliptin’ and an inhibitor of the enzyme DPP-4 (dipeptidyl peptidase-4), which is involved in the inactivation of the incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide). Both incretin hormones are involved in the physiological regulation of glucose homeostasis and these hormones are rapidly degraded by the enzyme DPP-4.¹ Linagliptin selectively inhibits DPP-4, which leads to a glucose-dependent increase in insulin secretion and a reduction in glucagon secretion thus resulting in an overall improvement in glucose homeostasis.¹ DPP-4 inhibitors prolong the action of GLP-1 and GIP by working in a glucose-dependent way.^2,3

Increase glucose dependent insulin secretion leading to increased glucose utilisation by muscle and adipose tissue.¹

Increase glucose dependent glucagon suppression leading to decreased hepatic glucose release improving overall glucose control.¹

Linagliptin is excreted primarily via the bile.¹

Only 5% of Linagliptin is excreted through the kidney and it can therefore be used in patients at any stage of renal function.¹

Proportions of medication excreted via the kidney

Infographic comparison chart of Linagliptin and other drugs excreted via the kidney

Please refer to the individual product SmPC for full information. Renal monitoring should be undertaken as per NICE guidelines.

Simple dosing and administration

Patients and practitioners can harness the simplicity of one dose, once daily, for adult patients with type 2 diabetes.^1†

Established safety profile via clinical studies

Cardiovascular (CV) safety is an important concern when managing adult patients with type 2 diabetes (T2D). Linagliptin demonstrated a safety profile across a broad range of T2D patients in 2 CVOTs including over 13,000 patients.^8-11*

Simplicity of Linagliptin

Linagliptin is the only globally available DPP-4i that combines proven efficacy¹², a demonstrated CV and kidney safety profile^8,11 and the convenience of always one dose, once daily.¹

Abbreviations:

3P-MACE: 3-point major adverse cardiac events; CV: cardiovascular; CVOT: cardiovascular outcome trial; MI: myocardial infarction; T2D: type 2 diabetes.

Footnotes

*
CARMELINA® and CAROLINA® included 6,979 and 6,033 patients respectively.^8,11 Primary endpoint for these trials: Time to first occurrence of any of the following CV components: CV death (including fatal stroke and fatal MI), non-fatal MI (excluding silent MI), or non-fatal stroke (3P-MACE).^8,11
†
Sulphonylureas and insulin are known to cause hypoglycaemia. Therefore, caution is advised when linagliptin is used in combination with a sulphonylurea and/or insulin. A dose reduction of the sulphonylurea or insulin may be considered (Linagliptin SmPC).

References

Linagliptin Summary of Product Characteristics. SmPC available at EMC.
Drucker DJ. Expert Opin Invest Drugs 2003;12:87-100.
Ahrén B. Curr Diab Rep 2003;3:365-372.
Sitagliptin Summary of Product Characteristics. SmPCs available at EMC.
Vildagliptin Summary of Product Characteristics. SmPC available at EMC.
Saxagliptin Summary of Product Characteristics. SmPCs available at EMC.
Alogliptin Summary of Product Characteristics. SmPCs available at EMC.
Rosenstock J et al. JAMA 2019;321(1):69–79.
Rosenstock J, et al. Cardiovasc Diabetol. 2018;17:39.
Marx N, et al. Diab Vasc Res. 2015;12:164–74.
Rosenstock J, et al. JAMA. 2019;322(12):1155–1166.
Del Prato S, et al. J Diab Compl. 2013; 27:274-9.

Linagliptin is indicated in adults with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycaemic control as:

monotherapy when metformin is inappropriate due to intolerance, or contraindicated due to renal impairment
in combination with other medicinal products for the treatment of diabetes, including insulin, when these do not provide adequate glycaemic control

PC-GB-112451 | May 2026

Reporting adverse events

Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Boehringer Ingelheim Drug Safety on 0800 328 1627 (freephone).

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