GLIPTINS

Glucose homeostasis in human body is regulated by number of hormones(insulin, glucagon etc.) through number of mechanisms.Gastrointestinal tract plays a vital role in maintaining normal blood glucose levels by secreting hormones like "glucagon like peptide" (GLP) and "glucose dependent insulinotropic polypeptide" (GIP).These hormones are known as incretins and regulate glucose homeostasis by:-

1. Stimulating insulin secretion.

2. Inhibiting glucagon synthesis.

3. Delaying gastric emptying.

Incretins secreted in gastrointestinal tract are rapidly inactivated by the enzyme called "dipeptidyl peptidase -4 (DPP-4).Gliptins are novel oral anti-diabetic medication that prolong the actions of endogenous incretins (GLP) by antagonising the effect of DPP-4.Gliptins that are currently in use include vildagliptin ,sitagliptin and saxagliptin.Gliptins are prescribed for Diabetes type-2 as monotherapy or in combination with other oral hypoglcemic drugs.Some of the adverse effects of Gliptins may include headache,dizziness,sore throat and running nose.

α- GLUCOSIDASE INHIBITORS

α-glucosidases are the enzymes that help in the digestion of carbohydrates in small intestines and α-glucosidase inhibitors are the drugs that inhibit α-glucosidases therefore slows down the absorption of polysacharides and sucrose.α-glucosidase inhibitors have mild anti-hyperglycemic action and are used as an adjuvant to diet or in combination with other oral hypoglycemic drugs.α-glucosidase inhibitors whic are in use are:-

1. Acarbose :- it is a complex oligosaccharide which inhibits α-glucosidases.Acarbose may prove helpful to control postprandial hyperglycemia.Total daily dose of acarbose is 150-300 mg taken in three divided doses at the begining of each big meal.Most common side effect associated with its use is loose stools and intestinal flatulence.

2. Voglibose :- voglibose delays glucose absorption in small intestines and prevent postprandial glucose rise.Daily dose of voglibose is 200-30mcg thrice daily.

3. Miglitol :- Another member from this class is miglitol and the mechanism of action is same as that of other members of this group.Dosage of miglitol is 25mg thrice daily in the begining of each big meal.

4. Guargum :- It is dietary fibre (polysaccharide) from indian cluster beans(Guar).It delays gastric emptying and absorption of carbohydrates thus beneficial for lowering postprandial blood glucose levels.Guargum is taken either just before or with big meals in daily dose of 2.5-5g in divided doses.


don't take this drug unless prescribed by your physician.


 

THIAZOLIDINEDIONES

This class of oral anti-diabetic drugs are selective agonists for the
nuclear 'peroxisome proliferator-activated receptor' which enhances the transcription of several insulin responsive genes . Thiazolidinediones are used to treat type2 diabetes mellitus and their glucose lowering action  without increasing the levels of circulating insulin can be explained as :-

1. Improving the entry of glucose into muscle and fat cells by stimulating GLUT4 expression.

2. Suppresing hepatic gluconeogenesis(glucose production in liver).

3. Reversing insulin resistance by activating the genes regulating lipogenesis in fat cells.

4. Apart from reversing insulin resistance pioglitazone lowers serum triglyceride level and raises HDL level thus improving lipid metabolism.


Two members of this group are Rosiglitazone and pioglitazone but Rosiglitazone is no longer in use because of serious liver toxicity caused by it,therefore thiazolidinediones are contraindicated in liver diseases.Pioglitazone can be used as monotherapy or in combination with sulphonylureas or metformin.


Drug                           Plasma      Duration     Daily     No. of doses
                                     t1/2 (hrs)             of action               dose              per day


1. Rosiglitazone                               4                      12-24                  4-8 mg               1-2

2. Pioglitazone                                 3-5                    24                      15-45                   1


Some of the adverse effects associated with thiazolidinedione use are edema, weight gain, headache, myalgia and anaemia.


Don't take this drug unless prescribed by your physician.



 

MEGLITINIDE ANALOGUES

This class of oral hypoglycemic drugs are also insulin secretagogues and cause release of insulin from the beta cells of the pancreas.Like sulphonylureas, meglitinide analogues bind to the sulphonylurea receptors of the beta cells but stimulates the first phase of insulin secretion resulting in rapid onset short lasting insulin release, therefore it is given before each meal to control post prandial hyperglycemia and has no effect on fasting blood glucose. .Maglitinide analogues are prescribed for type2 diabetes mellitus and are used as an alternative to sulphonylureas or in combination with metformin. Meglitinide analogues that are in use are :-


Drug               Plasma       Duration         Daily dose      No. of doses
                               t1/2 (hrs)                  of action                                      per day

1.Repaglinide.    <1             2-3(hrs)               1.5-8 mg                3-4

2.Nateglinide.     1.5            2-3(hrs)                180-480 mg           3-4


Adverse effects :-Some of the adverse effects of maglitinide analogues are dizziness, nausea and joint pain.



Don't take this drug unless prescribed by your doctor.

METFORMIN (BIGUANIDES)

Biguanides are oral hypoglycemic drugs used alone or in combination with other oral hypoglycemic agents to treat type2 diabetes mellitus.Two members of this class are metformin and phenformin,however phenformin has been withdrawn from many countries because of increased incidence of lactic acidosis. Biguanides are the first line oral hypoglycemic drugs for type2 diabetes but are also used in other conditions associated with insulin resitance.Biguanides are not insulin secretagogues, ie;does not stimulate insulin beta cells of the pancreas to secrete insulin therfore does not cause hypoglycemia except in overdose.The mechanisms by which biguanides lower blood glucose level are as follows:-

1. Biguanides suppress hepatic gluconeogenesis(synthesis of glucose in liver) and glucose output from liver.

2. Biguanides promote insulin mediated glucose disposal in muscle and fat cells thus decreasing the insulin resistance of the body to fat and mucle cells.

3. Biguanides increase peripheral uptake of glucose by enhancing anaerobic glycolysis.

4. Biguanides inhibit intestinal absorbtion of sugars(hexoses) ,vitB and aminoacids.

5. Biguanides also have anorexigenic property ,ie; overall food intake may be reduced which contributes to weight loss.

Biguanides that are in use :-

Drug                  Half life     Duration    Daily dose     No. of doses
                           in hrs.        of action                             per/day


1. Phenformin      3-10          8-12            25-150 mg          1-3

2. Metformin       1.5-3          6-8              0.5-2 mg             2-4


Adverse effects :-The most serious complication associted with biguanide use is lactic acidosis,however it is less common with metformin compared to phenformin.Metformin also inhibits absorbtion of vit.B12 and may cause Vit B12 deficiency.Apart from that high doses of metformin may cause adverse effects like abdominal pain, metallic taste and tiredness.