Gliptins

background

New drugs for DM

Researchers used to believe that insulin was released in direct response to increasing blood glucose levels But then they noticed an odd thing:
Injecting glucose into the bloodstream doesnt raise insulin levels as much as giving the same amount of glucose by mouth.

An unseen drama unfolds inside your body:

In response to a meal, Hormones called incretins or active glucagon-like peptide-1 (GLP-1) is secreted by the L cells of the intestines.

New drugs for DM

Incretins race from the gut to the pancreas and tell that organ to produce more insulin. But, a killer enzyme called dipeptidyl peptidase IV (DPP4) gives chase & destroys it Drugs targeting the incretin pathway are the latest addition to the available antidiabetes agents.

New drugs for DM

Without the presence of an Incretin-based therapy , GLP-1 is rapidly inactivated and degraded by the enzyme dipeptidyl peptidase IV (DPP4); Incretin-based therapy is either delivered:
1. orally (dipeptidyl peptidase-4 [DPP-4]) inhibitors or 2. injected subcutaneously (glucagon-like peptide1 [GLP-1] mimetics and analogues). 3. Active GLP-1 causes the pancreas to increase insulin release. With a gliptin, one binds the DPP4, allowing GLP-1 to remain active.

India
Eli Lilly has Byetta (exenatide injection) [GLP-1 agonist] There are 6 DPP-4 inhibitors currently available
1. Sitagliptin (Merck & Co. Januvia), 2. Vildagliptin (Novartis, Galvus), 3. Saxagliptin (BMS, Onglyza), 4. Linagliptin (Boehringer Ingelheim, Tradjenta), 5. Dutogliptin (by Phenomix Corporation), 6. Gemigliptin (by LG Life Sciences,Korea)

Modes of action of incretin based drugs

Modes of action of incretin based drugs

Dipeptidyl peptidase-4 inhibitors are effective with a low incidence of hypoglycemia and no weight gain either as a single or combination therapy with lowering of
1. glycated hemoglobin, fasting and postprandial glucose levels.

HUMALOG

Humalog
Humalog is a mealtime insulin with a more rapid onset and a shorter duration of action than regular human insulin. When given subcutaneously, Humalog should be given within 15 minutes before or immediately after a meal and should generally be used in regimens that include an intermediate- or long-acting insulin.

Humalog
Humalog is engineered through recombinant DNA technology, the penultimate lysine and proline residues on the C-terminal end of the B-chain are reversed.

Humalog
This modification does not alter receptor binding, but blocks the formation of insulin dimers and hexamers. This permits larger amounts of active monomeric insulin to be immediately available for postprandial injections