This document discusses several classes of oral antihyperglycemic drugs used to treat type 2 diabetes, including their pharmacological actions, clinical uses, dosages, and adverse effects. It describes biguanides like metformin, sulfonylureas, thiazolidinediones, meglitinides, alpha-glucosidase inhibitors, and DPP-4 inhibitors. It also discusses treating and managing common long-term complications of diabetes such as retinopathy, neuropathy, gastroparesis, nephropathy, and peripheral vascular disease.

1. Jehan Zeb khan
Pharm.D

2. Biguanides
Sulfonylureas
Meglitidines
Thiazolidinediones
Alpha-glucosidase inhibitors
Dipeptidyl Peptidase-4 (DPP-4) Inhibitors

3.  Biguanides:
Metformin (Glucophage)
Phenformin
 Sulfonylureas:
1ST Generation:Tolbutamide, Chlorpropamide,Tolazolide
2nd Generation: glyburide, glibenclamide, glipizide, glimipride,
 Thiazolidinediones
Pioglitazone, rosiglitazone, troglitazone
 Meglitinides
Repaglinide
 Alpha-glucosidase inhibitors
Acarbose, Meglitol.
 Dipeptidyl Peptidase-4 (DPP-4) Inhibitors
Valdegliptin, sitagliptin

4. Pharmacological Effects:
>increase insulin sensitivity
>Increases glucose uptake and utilisation
>reduces hepatic glucose production
>decreases glucose absorption from GIT
>decrease plasma glucagon level
Decrease blood glucose
>Metformin has no direct effect on the β cells, although insulin levels
are reduced, reflecting increases in insulin sensitivity.

5. Clinical uses:
Hyperglycemia due to ineffective insulin action.
>Type II diabetes +-Tzd or insulin
secretagogues
>Prevention of type II DM
Dosage: 500mg to maximum 2.55gm daily with
the lowest effective dose being
recommended. Dosage always be divided
since dose greater than 1000mg provoke GI-
upsets.

6. Adverse Effects:
>GI-Upsets: anorexia, nausea, vomiting,
abdominal discomfort, diarrhea.
>DecreaseVitaminB12 absorption.
>lactic acidosis: more common with phenformin
than with metformin.
Contraindications:
Renal disease
Hepatic disease
Conditions predisposing to tissue anoxia

7. Pharmacological actions:
>Decrease insulin resistance
>Enhance insulin sensitivity
>Increase uptake and utilization of glucose in
muscles and adipose tissues

8. Indications:
 As monotherapy or in combination with biguanides or
Sulfonylureas in type II DM
Adverse effects:
 Fluid retention
 Weight gain
 Increased fracture rate
 Anovulatory women may starts ovulation and risk of
pregnancy
 Hepatotoxicity
Contraindications:
 Liver disease
 Heart failure
 pregnancy

9. Pharmacological action:
Inhibit alpha glucosidases (sucrase,
maltase,dextranase,glycoamylase) that
converts complex starches, oligosaccharides
and disaccharides to their respective
monosacharides.
Their inhibition causes decrease absorption of
glucose.
How to treat hypoglycemia here?!

10. Adverse effects:
Flatulence, diarrhea, abdominal pain.

11. Pharmacological actions:
 Insulin release from beta cells of pancreas
Through inhibition of ATP-sensitive potassium
channels that results in depolarization and
opens calcium channels with results in influx
of calcium ions and the release of insulin.
 Reduces glucagon secretion

12. Uses:
Sulfonylureas are used primarily for the treatment of
diabetes mellitus type 2. Sulfonylureas are ineffective
where there is absolute deficiency of insulin
production such as in type 1 diabetes
Adverse effects:
Hypoglycemia as a result of excesses in insulin release.
Abdominal upsets, headache and hypersensitivity
reactions.
Impairment of liver or kidney function increase the risk
of hypoglycemia, and are contraindications.

13.  Retinopathy: Patients with established
retinopathy should be examined by an
ophthalmologist at least every 6 to 12 months.
 Neuropathy: Paresthesias, numbness, or pain
can be the predominant symptom. If neuropathy
is painful, symptomatic therapy is empiric,
including low-dose tricyclic antidepressants,
anticonvulsants (gabapentin, pregabalin,
carbamazepine, and maybe phenytoin),
duloxetine, venlafaxine, topical capsaicin, and
various pain medications, including tramadol
and nonsteroidal antiinflammatory drugs.

14.  Gastroparesis can be severe and debilitating.
Improved glycemic control, discontinuation of
medications that slow gastric motility, and use of
metoclopramide.
 Patients with orthostatic hypotension may require
mineralocorticoids or adrenergic agonists.
 Diabetic diarrhea is commonly nocturnal and
frequently responds to a 10- to 14-day course of an
antibiotic such as doxycycline or metronidazole.
Octreotide may be useful in unresponsive cases.
 Erectile dysfunction is common, and initial treatment
should include one of the oral medications currently
available (e.g., sildenafil, vardenafil, tadalafil).

15.  Nephropathy:
 Glucose and blood pressure control are most
important for prevention of nephropathy, and blood
pressure control is most important for retarding the
progression of established nephropathy.
 Angiotensin-converting enzyme inhibitors and
angiotensin receptor blockers have shown efficacy in
preventing the clinical progression of renal disease in
patients with type 2 DM. Diuretics are frequently
necessary due to volume-expanded states and are
recommended second-line therapy.

16.  PeripheralVascular Disease and Foot Ulcers
 Coronary Heart Disease