Emerging drug candidates of dipeptidyl peptidase IV (DPP IV) inhibitor class for the treatment of Type 2 Diabetes.
Dipeptidyl peptidase IV (DPP IV) is a key regulator of insulin-stimulating hormones, glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), thus it is a promising target for the treatment of Type 2 Diabetes mellitus (T2DM). Inhibition of plasma DPP IV enzyme leads to enhanced endogenous GLP-1 and GIP activity, which ultimately results in the potentiation of insulin secretion by pancreatic beta-cells and subsequent lowering of blood glucose levels, HbA[1(c)], glucagon secretion and liver glucose production. Various classes of structurally different DPP IV inhibitors are currently being explored and few of them such as Sitagliptin and Vildagliptin were successfully launched. These drugs have been approved as a once-daily oral monotherapy or as a combination therapy with current anti-diabetic agents like pioglitazone, glibenclamide, metformin etc. for the treatment of T2DM. Several other novel DPP IV inhibitors are in pipeline. The present review summarizes the latest preclinical and clinical trial data of different DPP IV inhibitors with a special emphasis on their DPP8/9 fold selectivity and therapeutic advantages over GLP-1 based approach.
Gupta
Rajesh
R
New Drug Discovery, R & D Center, Matrix Laboratories Limited, Anrich Industrial Estate, Bollaram, Jinnaram Mandal, Medak District, Andhra Pradesh, 502 325, India.
Walunj
Sameer S
SS
Tokala
Ranjeet K
RK
Parsa
Kishore V L
KV
Singh
Santosh Kumar
SK
Pal
Manojit
M
D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology; D018819:Dipeptidyl Peptidase 4 / Q000009:adverse effects*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011759:Pyrrolidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000068900:Sitagliptin Phosphate; D013379:Substrate Specificity; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000077597:Vildagliptin
D054873:Dipeptidyl-Peptidase IV Inhibitors; D015507:Drugs, Investigational; D007004:Hypoglycemic Agents; D009570:Nitriles; D011719:Pyrazines; D011759:Pyrrolidines; D014230:Triazoles; D018819:Dipeptidyl Peptidase 4; D000077597:Vildagliptin; D000218:Adamantane; D000068900:Sitagliptin Phosphate