This document summarizes various oral hypoglycemic drugs used to treat type 2 diabetes mellitus. It discusses the mechanisms of action, pharmacokinetics, side effects, drug interactions, and important considerations for sulfonylureas, meglitinides, DPP-4 inhibitors, biguanides, thiazolidinediones, alpha-glucosidase inhibitors, amylin analogues, dopamine D2 agonists, SGLT2 inhibitors, bile acid binding resins, aldose reductase inhibitors, and dual PPAR agonists. The document provides detailed information on the classification, properties and use of these different classes of antidiabetic medications.

1. ORAL HYPOGLYCEMIC DRUGS
DIABETES MELITTUS HAS BEEN CLASSIFEID AS
FOLLOWS-
TYPE I(IDDM/JUVENILE ONSET DM)
TYPE II(NIDDM/MATURITY ONSET DM)
TYPE III(SPECIFIC GENETIC DEFECT LIKE MATURITY
ONSET DIABETES OF YOUNG{MODY}),OTHER
ENDOCRINE DISORDER,PANCREATECTOMY)
TYPE IV(GESTATIONAL DM)
THESE ARE THE DRUGS WHICH ARE MAINLY USED IN
TYPE II DIABETES MELLITUS WHICH LOWERS BLOOD
GLUCOSE.

2. CLASSIFICATION
• A.ENHANCE INSULIN SECRETION:-
1.SULFONYLUREAS (KATP CHANNEL BLOCKERS)
1ST GEN-TOLBUTAMIDE,TOLAZOMIDE,CHLORPROPAMIDE
2ND GEN-GLIBENCLAMIDE(GLYBURIDE),
GLIMEPRIDE,GLIPIZIDE,GLICLAZIDE
2.GLUCAGON LIKE PEPTIDE(GLP-1) RECEPTOR AGONIST
EXENETIDE ,LIRAGLUTIDE
3.MIGLITINIDE/PHENYLALANINE ANALOGUE
REPAGLINIDE,NATEGLINIDE
4.DIPEPTIDYL PEPTIDASE-4(DPP4) INHIBITORS
SITAGLIPTIN,VIDAGLIPTIN,LINAGLIPTIN, SAXAGLIPTIN,GEMIGLIPTIN
ALOGLIPTIN
B.OVERCOME INSULIN RESISTANCE

3. SULFONYLUREAS(KATP CHANNEL
BLOCKERS)
• THESE ARE INSULIN SECRETAGOGUES CAUSING INSULIN RELEASE
FROM BETA CELLS OG PANCREAS.
MOA-
1.THEY BLOCK THE ATP DEPENDENT POTASSIUM CHANNELS
RESTRICTING K IONS INFLUX RESULTING IN DEPOLARISATION AND
INFLUX OF Ca ION FROM INTRACELLULAR STORES.THESE Ca IONS
CAUSES FUSION OF INSULIN CONTAINING INTRACELLULAR GRANULES
WITH THE PLASMA MEMBRANE AND EXOCYTOTIC RELEASE OF INSULIN
OCCURS.
2.REDUCTION IN HEPATIC GLUCOSE PRODUCTION.
3.INCREASE IN PERIPHERAL INSULIN SENSITIVITY BY INCREASING
INSULIN RECEPTORS.
NOTE:-INSULIN RELEASE OCCURS EVEN AT LOW GLUCOSE LEVEL

4. • PHARMACOKINETICS:- GIVEN ORALLY,THESE DRUGS
BINDS TO SERUM PROTEINS.
METABOLISED BY LIVER AND EXCRETED IN URINE.
ADVERSE EFFECT:-
HYPOGLYCEMIA IS VERY COMMON.
WEIGHT GAIN
NAUSEA,VOMITING,FLATULANCE,DIARRHOEA OR
CONSTIPATION, HEADACHE, PARAESTHESIA ARE MILD
AND INFREQUENT.
RASHES,PURPURA, PHOTOSENSITIVITY ARE RARE.

5. • SHOULD BE CAUTIOUSLY USED IN PATIENT WITH
HEPATIC OR RENAL INSUFFICIENCY BECAUSE
DELAYED EXCRETIONMAY CAUSE ACCUMULATION
OF DRUGS AND CAUSE HYPOGLYCEMIA.
• THEY ARE SECRETED IN MILK HENCE SHOULD NOT
BE GIVEN TO LACTATING MOTHERS.
NOTE:-GLYBURIDE HAS MINIMAL TRANSFER ACROSS
THE PLACENTA AND CAN BE SAFE ALTERNATIVE TO
INSULIN THERAPY FOR DIABETES IN PREGNENCY.

6. DRUG INTERACTION
ENHANCE ACTION OF SULFONYLUREAS:-
SALICYLATES, SULFONAMIDES BY DISPLACING FROM
PROTEIN BINDING.
KETOCONAZOLE,SULFONAMIDES,WARFARIN, ACUTE
ALCOHOLISM,CHLORAMPHENICOL INHIBITS
METABOLISM.
SALICYLATES,PROPRANOLOL,THEOPHYLLINE
PROLONGS PHARMACODYNAMICS.
DECREASES ACTION OF SULFONYLUREAS:-
PHENYTOIN,PHENOBARBITONE,RIFAMPICIN, CHRONIC
ALCOHOLISM,CORTICOSTEROID,THIAZIDE, OCP ETC.

7. FEW IMPORTANT ONE LINERS
• CHLORPROPAMIDE IS WITHDRAWN DUE TO
ITS LONG DURATION OF ACTION(2 DAYS)
OTHER SIDE EFFECTS ARE- SIAD(SYNDROME OF
INAPPROPRIATE ANTIDIURESIS),
AGRANULOCYTOSIS, CHOLESTATIC JAUNDICE,
DISULFIRAM LIKE REACTION.

8. MEGLITINIDE/D-PHENYLALANINE
ANALOGUES(KATP CHANNEL BLOCKER)
• THESE ARE KATP CHANNEL BLOCKERS WITH A QUICK AND SHORT
LASTING INSULINEMIC ACTION.
MOA:-THERE ACTION IS DEPENDENT ON FUNCTIONING BETA CELLS.
IT IS SAME AS SULFONYLUREAS.
PHARMACOKINETICS- ABSORBED ORALLY
METABOLISED TO INACTIVE PRODUCTS BY CYP3A4 IN
LIVER AND EXCRETED IN BILE.
REPAGLINIDE- IT IS GIVEN BEFORE EACH MAJOR MEAL AS IT CAN
CONTROL POST PARANDIAL HYPERGLYCEMIA.
S/E- MILD HEADACHE, DYSPEPSIA, ARTHRALGIA, WEIGHT GAIN.
IT SHOULD BE AVOIDED IN LIVER DISEASE.
NATEGLINIDE- S/E- DIZZINESS,NAUSEA, FLU LIKE SYMPTOMS AND
JOINT PAIN.

9. DIPEPTIDYL PEPTIDASE-4(DPP-
4)INHIBITORS
• DPP-4 ARE THE ENZYME WHICH CAUSES DEGRADATION
OF GLP-1(INCRETINS)
MOA- DPP-4 INHIBITORS INCREASES INCRETIN
LEVELS(GLP-1 AND GIP) WHICH INHIBITS GLUCAGON
RELEASE,WHICH IN TURN INCREASES INSULIN
SECRETION,DECREASES GASTRIC EMPTYING AND
DECREASES BLOOD GLUCOSE LEVELS.
SITAGLIPTIN:- IT IS COMPTETIVE AND SELECTIVE DPP-4
INHIBITOR.
IT BOOSTS POST PARANDIAL INSULIN RELEASE,
DECREASES GLUCAGON SECRETION AND LOWERS MEAL
TIME AS WELL AS FASTING BLOOD GLUCOSE IN TYPE II
DM.

10. • IT DOES NOT CAUSES WEIGHT LOSS.
• LOW RISK OF HYPOGLYCEMIA WHEN USED
ALONE.
• LOWERS HbA1C AS SAME AS METFORMIN.
• USED AS MONOTHERAPY WHEN METFORMIN
CANNOT BE USED.
• AS AN ADJUVANT DRUG IT IS USED WHEN
BLOODSUGAR IS NOT WELL CONTROLLED BY
METFORMIN/SU/ PIOGLITAZONES OR
INSULINS.

11. • PHARMACOKINETICS:- ABSORBED ORALLY.
EXCRETED IN URINE.
DOSE REDUCTION IS NEEDED IN RENAL
IMPAIRMENT BUT NOT IN LIVER DISEASES.
S/E:- NAUSEA, LOOSE STOOL, HEADACHE, RASHES,
ALLERGIC REACTIONS, OEDEMA
RARELY NASOPHARYNGITIS AND COUGH,
PANCREATITIS.

12. • VIDAGLIPTIN:- IT BINDS TO DPP-4 COVALENTLY
RESULTING IN VERY SLOW DISSOCIATION CAUSING
PERSISTANT DPP-4 INHIBITION EVEN AFTER
CLEARANCE OF FREE DRUG FROM
CIRCULATION.DUE TO THIS,DESPITE OF SHORT
PLASMA T1/2 OF 2-4 HRS IT HAS DURATION OF
ACTION OF 12 -24 HRS.
PHARMACOKINETICS:- ELIMINATION IS BY HEPATIC
METABOLISM.
20-25% IS EXCRETED UNCHANGED IN URINE.
DOSE REDUCTION IS NEEDED IN LIVER AND KIDNEY
DISEASE.
SAXAGLIPTIN:-SAME AS VIDAGLIPTIN.
METABOLISED BY CYP3A4.

13. ONE LINERS
REVERSIBLE DPP-4 INHIBITORS-
SITAGLIPTIN AND ALOGLIPTIN
IRREVERSIBLE DPP-4 INHIBITORS-
VIDAGLIPTIN AND SAXAGLIPTIN
RECENT STUDIES SHOWS JOINT PAIN AS
IMPORTANT SIDE EFFECT.

15. BIGUANIDES
• THESE ARE THE DRUGS WHICH DOESNOT CAUSE HYPOGLYCEMIA IN
NON DIABETICS AND EVEN IN DIABETICS,EPISODES OF
HYPOGLYCEMIA ARE RARE.
MOA-PRESENCE OF INSULIN IS ESSENTIAL FOR ITS ACTION HENCE IT IS
NON FUNCTIONAL IN PANCREATECTOMISED AND IN TYPE I DIABETICS.
THERE IS ACTIVATION OF AMP DEPENDENT PROTEIN KINASE WHICH
CAUSES-
*SUPPRESSION OF GLUCONEOGENESIS.
*ENHANCES GLUCOSE UPTAKE AND DISPOSE IT TO SKELETAL MUSCLE
AND FAT.
*PROMOTES PERIPHERAL GLUCOSE UTILIZATION THROUGH
ANAEROBIC GLYCOLYSIS BY INTERFERING WITH MITOCHONDRIAL
RESPIRATORY CHAIN.
*RETARDS INTESTINAL ABSORPTION OF GLUCOSE.

16. • PHARMACOKINETICS:- ABSORBED ORALLY,NOT BOUND TO
SERUM PROTEIN.
EXCRETION IS VIA URINE.
IT ACCUMULATES IN RENAL FAILURE AND INCREASES RISK OF
LACTIC ACIDOSIS.
A/E:- GASTROINTESTINAL DISTURBANCES SUCH AS
PAIN,ANOREXIA, BLOATING, NAUSEA,METALLIC TASTE,MILD
DIARRHOEA AND TIREDNESS.
VIT B12 DEFECIENCY BY INTERFERING IN ITS ABSORPTION.
RARELY LACTIC ACIDOSIS.
C/I:- HYPOTENSION,HEART FAILURE,SEVERE RENAL HEPATIC AND
RESPIRATORY DISEASE,ALCOHOLICS.
DRUG INTERACTION:-CIMETIDINE AND FUROSEMIDE COMPETE
WITH METFORMIN EXCRETION.

17. FEW ONE LINERS
• WEIGHT LOSS PROMOTING.
• PREVENT MACRO AND MICROVASCULAR
COMPLICATION.
• SLOW DOWN BETA CELL
EXHAUSTION/FAILURE IN TYPE II DM.
• REDUCES HbA1C.
• CAN BE USED TO IMPROVE OVULATION AND
FERTILITY IN PCOD.

18. THIAZOLIDINEDIONES
• THESE ARE SELECTIVE AGONISTS FOR THE NUCLEAR
PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR
GAMA(PPAR GAMA).
MOA:- THESE DRUGS BINDS WITH PPAR GAMA
NUCLEAR HORMONE RECEPTOR.LIGANDS FOR PPAR
GAMA REGULATE ADIPOCYTE PRODUCTION AND
SECRETION OF FATTYACIDS AS WELL AS GLUCOSE
METABOLISM,RESULTING IN INCREASE INSULIN
SENSITYVITY IN ADIPOSE TISSUE,LIVER AND SKELETAL
MUSCLE.
HEPATIC GLUCONEOGENESIS IS ALSO SUPPRESSED.

19. • PIOGLITAZONE ALSO LOWERS SERUM
TRYGLYCERIDES LEVEL AND RAISES HDL WITHOUT
MUCH CHANGE IN LDL LEVEL.
• PHARMACOKINETICS:- ABSORBED ORALLY AND
BOUND TO SERUM ALBUMIN.
UNDERGO EXTENSIVE METABOLISM BY
CYTOCHROME P450 ISOENZYME.
PIOGLITAZONE:-RENAL ELIMINATION IS
NEGLIGIBLE,METABOLITES ARE EXCRETED IN BILE AND
ELIMINATED IN FECES.
ROSIGLITAZONE:-METABOLISED ARE EXCRETED IN
URINE.

20. • A/E:- PLASMA VOLUME EXPANSION.
OEDEMA
WEIGHT GAIN
HEADACHE
MYALGIA AND MILD ANEMIA
CHF MAY BE PRECIPITATED OR WORSENED
IN VERY FEW CASES CAUSES
HEPATOTOXICITY.
OSTEOPENIA AND INCREASED FRACTURE RISK

21. ALFA-GLUCOSIDASE INHIBITORS
• IT WORKS BY PREVENTING DIGESTION OF
CARBOHYDRATE.
MOA- DRUGS INHIBITS REVERSIBLY ALFA-
GLUCOSIDASES WHICH IS A FINAL ENZYME FOR
CARBOHYDRATE DIGESTION CAUSING SLOWING
DOWN AND DECREASES DIGESTION AND
ABSORPTION OF POLYSACCHARIDES AND SUCROSE.
GLP-1 RELEASE IS ALSO PROMOTED.
MAINLY REDUCES POSTPARANDIAL HYPERGLYCEMIA.

22. • PHARMACOKINETICS:- ACARBOSE IS METABOLISED
BY INTESTINAL BACTERIA AND EXCRETED IN THE
URINE.
MIGLITOL IS WELL ABSORBED BUT HASNO
SYSTEMIC EFFECT,EXCRETED UNCHANGED BY KIDNEY.
A/E:-GI DISTURBANCE SUCH AS
FLATULANCE,DIARRHOEA, CRAMPING.
HEPATIC TRANSAMINASES MAY RISE.
NOTE:-IT IS ONLY ORL ANTIHYPERGLYCEMIC
EFFECTIVE IN TYPE I DM.
ACARBOSE CAN REDUCE FIBRINOGEN LEVEL.

23. AMYLIN ANALOGUE
• AMYLIN IS ALSO CALLED AMYLOID POLYPEPTIDE
PRODUCED BY PANCREATIC BETA CELLS AND ACT IN
BRAIN(HIND BRAIN) TO REDUCE GLUCAGON
SECRETION FROM ALFA CELLS.
• IT SUPPRESSES APPETIET.
• DELAYS GASTRIC EMPTYING.
• IT IS APPROVED FOR BOTH TYPE I AND II DM,ONLY IN
COMBINATION WITH ISULIN.
• GIVEN S/C BEFORE MEAL.
• REDUCTION IN BODY WEIGHT IS ADDITIONAL BENEFIT.

24. DOPAMINE D2 AGONISTS
• BROMOCRIPTINE:-WHEN TAKEN EARLY IN THE
MORNING IT ACTS ON HYPOTHALAMIC
DOPAMINERGIC SYSTEM TO CONTROL CIRCARDIAN
RHYTHM OF HORMONE RELEASE AND RESET IT TO
REDUCE INSULIN RESISTANCE.

25. SODIUM GLUCOSE CO-TRANSPORT-2
INHIBITOR(SGLT2)
• GLUCOSE WHICH IS FILTERED AT GLOMERULUS IS
REABSORBED IN PCT WITH THE HELP OF SGLT-2.
• WHEN SGLT-2 IS INHIBITED, GLYCOSURIA IS
INDUCED RESULTING IN LOWERING OF BLOOD
GLUCOSE IN TYPE II DM AS WELL AS CAUSES
WEIGHT LOSS.
A/E-URINARY AND GENITAL INFECTION.
ELECTROLYTE IMBALANCE
INCREASED URINARY FREQUENCE
DIABETIC KETOACIDOSIS

26. BILE ACID BINDING RESINS
• IT DECREASES THE ABSORPTION OF GLUCOSE
FROM GIT.

27. ALDOSE REDUCTASE INHIBITORS
• REDUCES THE CONVERSION OF GLUCOSE TO
SORBITOL,HENCE REDUCES THE DIABETIC
NEPHROPATHIC COMPLICATION.

28. DUAL PPAR AGONIST
• IT REDUCES BOTH LIPID AND GLUCOSE LEVEL.
• APPROVED FOR DIABETIC DYSLIPIDEMIA.

31. THANK YOU