Dipeptidyl peptidase 4 (DPP-4) inhibitors

Exert action, in part, by slowing the inactivation of the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP).

Dipeptidyl peptidase 4 (DPP-4) is a homodimeric type II transmembrane receptor identical to the leukocytes surface antigen CD 26 is also present a soluble, enzymatically active form in plasma.
DDP-4 is involved in multiple biologic processes including: insulin release, stromal cell derived factor 1-induced  homing of stem cells, hematopoietic cytokine activity, and T cell immune function.
They inhibit the enzyme that degrades glucagon-like peptide-1, and gastric inhibitory polypeptide.
DPP4  inhibitors can achieve a 0.6-0.9%  A-1 C reduction and are typically weight neutral.
On T cells CD26 or DPP-4  has a co-similarity function and enhancing T cell activation.

Gliptin class of drugs.

DPP-4 Inhibitors block an enzyme (DPP-4) that normally deactivates a protein (GLP-1) that keeps insulin circulating in the blood.

Oral medications that block DDP-4 and allow for endogenous levels of GLP-1 and GIP to increase.

These agents have the same effects as GLP-1 analogs, but are milder.

DDP-R inhibitors are better tolerated than GLP-1 analogs.

Novel class of oral antidiabetic medications that potentiate the glucose-dependent incretin effect for serum glucose reduction , and associated with an acceptable risk of hypoglycemia while achieving better glycemic control.

Slowing the deactivation process helps reduce sugar production, lowering blood glucose levels.

Increase the concentration of intestinally produced hormones GLP-1 and GIP which are decreased in patients with type 2 diabetes.

Incretin hormones are released by the intestine throughout the day and are increased in response to a meal.

Incretin hormones increase insulin secretion, suppress glucagon release, delay gastric emptying and cause satiety.

Slow the inactivation of the incrretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic Polypeptide (GIP).

DPP-4 inhibitors target postprandial glucose and decrease fasting plasma glucose levels.

Incretin hormones stimulate insulin release from pancreatic beta cells in response to meals and they are rapidly inactivated DPP-4 enzymes.

Oral agents that inhibited the degradation of GLP-1 and result in modest elevations of circulating GLP-1.

Not associated with weight gain.

These agents increase the concentration of incretin hormones in the bloodstream reducing fasting and postprandial glucose concentrations.

Agents include alogliptin (Nesina), sitagliptin (Januvia), saxagliptin (Onglyza), Linagliptin (Tradjenta).

All DPP-4 inhibitors, as monotherapy reduce hemoglobin A-1 C by 0.5%-0.8%.

All DPP-4 inhibitors may be dosed once daily.

The most common side effects or headache, increased respiratory infections, and urinar y tract infections.

They are associated with an increased risk of pancreatitis and are contraindicated in patients with a history of pancreatitis.

Januvia (sitagliptin phosphate) was the first of the DPP-4 inhibitors to be approved by the Food and Drug Administration.

Januvia is an oral medication which is taken once a day, either alone with diet and exercise, or in combination with other oral diabetes medications.

These agents mimic the action of incretin hormones which help the body make more insulin.

Only increase insulin when glucose is high, so are unlikely to cause hypoglycemia.

These agents palso slow the rate of digestion so that glucose enters the blood more slowly.

People on incretin mimetics feel full longer, which reduces food intake, which helps some people lose weight while on the medication.

Alogliptin, sitagliptin, , and saxagliptin require adjustments with renal impairment.

Linagliptin does not require adjustments in patients with renal impairment.

DDP-4 inhibitors has an increased risk for acute kidney injury compared with nonusers.

DDP-4 inhibitors associated with heart failure.

May be associated with inflammatory bowel disease.

One of every three patients with type two diabetes and chronic kidney disease receives inappropriate dosing of DPP-4 inhibitors, which is associated with a high risk of ED visits, severe hypoglycemia and mortality.

Sitagliptin, In combination with tacrolimus and sirolimus resulted in low incidence of grade IIto IV graft versus host disease by day 100 after myeloablative allogeneic hematopoetic stem cell transplantation: DDP-4 inhibitors decreases T cell activity.

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