Because of their pharmacokinetic characteristics, pharmacodynamic properties glucose-dependent glucose-lowering effect and good overall tolerability profile, DPP-4 inhibitors may have a key role to play in elderly patients [ ]. Other than the surrogate endpoint of improved glycemic control though, data on clinically relevant benefits of DPP-4 inhibitors in the treatment of type 2 diabetes mellitus in older adults is scarce.
DPP-4 inhibitors might have a lower risk of hypoglycemia compared to other antidiabetic drugs but data show conflicting findings for long-term benefits. Further studies are needed to guide specific recommendations [ ]. Dipeptidyl peptidase-4 DPP-4 inhibitors are oral diabetes medications that inhibit the enzyme DPP-4, a ubiquitous enzyme that is expressed on the surface of most cell types and deactivates a variety of other bioactive peptides, including glucose-dependent insulinotropic polypeptide GIP and glucagon-like peptide-1 GLP DPP-4 inhibitors thus affect glucose regulation by augmenting the incretin system.
Given the large number of substrates cleaved by DPP-4 with diverse effects particularly in the immune and endocrine systems, the long term safety of DPP-4 inhibitors in human studies merits careful consideration and analysis. Generally, the DPP-4 inhibitors comprise of a group of chemically diverse compounds, which differ in terms of their potency to inhibit the DPP-4 enzyme, their duration of action and their metabolism and elimination, as well as isolated compound-specific characteristics [ 44 ].
They are all apparently well tolerated side-effect profile resembles placebo and result in clinically meaningful reductions in blood glucose fasting and postprandial and HbA1c levels, with minimal risk of hypoglycemia and without weight gain. They are used without the need for dose titration and give broadly similar HbA1c lowering efficacy to other oral antidiabetic agents. At present, although there are some practical differences between the different DPP-4 inhibitors with respect to dosing frequency and their ability to be used in different patient subpopulations, there seems to be little to distinguish between them in terms of their efficacy as antidiabetic agents and their safety.
In particular, linagliptin might be a good choice as initial therapy in a patient with chronic kidney disease at risk for hypoglycemia. Other DPP-4 inhibitors may be used in the setting of chronic kidney disease with proper dose adjustment. On the other hand, their long-term benefits and durability of glycemic effects remain unclear. Hence, they are not recommended as initial therapy for treatment of T2D.
They do appear to be a reasonable second-line add-on therapy to metformin, especially in individuals at high risk for hypoglycemia i. Additionally, in high cardiovascular risk patients, the cardiac effects have been neutral, and other classes of antidiabetic medications in particular SGLT-2 inhibitors or GLP-1 agonists are preferred [ 63 ].
The risk of hospitalization for heart failure remains poorly understood, and risk factors such as prior heart failure and chronic kidney disease should be considered when prescribing this class of therapy [ 47 ].
National Center for Biotechnology Information , U. Published online Jul Konstantinos Makrilakis. Author information Article notes Copyright and License information Disclaimer. Thoma St. Received Jul 1; Accepted Jul This article has been cited by other articles in PMC. Abstract Type 2 diabetes mellitus is a growing global public health problem, the prevalence of which is projected to increase in the succeeding decades.
Keywords: Diabetes mellitus type 2, treatment, DPP-4 inhibitors. Introduction Diabetes mellitus DM is a complex, chronic illness requiring continuous medical care with multifactorial risk-reduction strategies in order to reduce complications.
The DPP-4 Enzyme Dipeptidyl peptidase-4 DPP-4 , originally described as a lymphocyte cell surface protein identical to the T-cell activation antigen cluster of differentiation CD , is a ubiquitously expressed transmembrane-spanning glycoprotein exopeptidase of kDa, that exerts biological activity through pleiotropic actions. DPP-4 Inhibitors There are five DPP-4 inhibitors in the market today, including sitagliptin, saxagliptin, linagliptin, alogliptin in the United States and Europe , and vildagliptin only available in Europe [ 44 ].
Table 1 Comparison of currently marketed DPP-4 inhibitors. Open in a separate window. Cardiovascular Effects All agents for treatment of hyperglycemia in diabetes are evaluated for efficacy in lowering blood glucose levels and overall safety and are subjected to particularly rigorous screening for cardiovascular safety through randomized controlled trials.
Mortality DPP-4 inhibitors do not appear to have any effect on overall mortality. Adverse Effects The DPP-4 inhibitors as a class appear to be very well tolerated, and rates of adverse effects have been low, and generally not different from a placebo or comparator. Use in Special Populations Patients with Renal Insufficiency Because most of DPP-4 inhibitors are eliminated renally, it is expected that their pharmacokinetic profile will be influenced by impairments in renal function and that their plasma levels will increase in proportion to renal failure [ 44 ].
Table 2 Dosage of DPP-4 inhibitors in renal and hepatic insufficiency. Conclusions Dipeptidyl peptidase-4 DPP-4 inhibitors are oral diabetes medications that inhibit the enzyme DPP-4, a ubiquitous enzyme that is expressed on the surface of most cell types and deactivates a variety of other bioactive peptides, including glucose-dependent insulinotropic polypeptide GIP and glucagon-like peptide-1 GLP Scheme 1.
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DPP-4 inhibitors work by blocking the action of DPP-4, an enzyme which destroys the hormone incretin. Incretins help the body produce more insulin only when it is needed and reduce the amount of glucose being produced by the liver when it is not needed. These hormones are released throughout the day and levels are increased at meal times. GLP-1 helps the body lower blood sugar levels by causing the pancreas to produce insulin after a meal.
So, more GLP-1 means more insulin production and lower glucose levels. DPP-4 inhibitors are used by people with type 2 diabetes.
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