This document provides information on drugs used to treat diabetes mellitus. It discusses the types of diabetes, signs and symptoms, and effects of insulin on metabolism. It describes various insulin preparations including short-acting, intermediate-acting, and long-acting insulins. It also discusses oral hypoglycemic drugs including sulfonylureas, glinides, biguanides, thiazolidinediones, and alpha-glucosidase inhibitors. The goals of diabetes treatment are to maintain normal blood glucose levels, promote normal metabolism, prevent complications, and prevent hypoglycemia.

1. Unit-1: Drugs used in
endocrine disorder
Antidiabetic Agents
Dr Muslim Abbas

2. Personal Information
• Name: Muslim Abbas
• Current Affiliation: Jinnah Medical and Dental College
• Current Position: Assistant Professor of Pharmacology
• I practice general dentistry at my own clinic in evening since 2013
• Qualification:
• B.D.S (Jinnah Medical and Dental College)-2012
• M.Phil. (University of Karachi) -2018

3. Diabetes Mellitus
• Diabetes mellitus is a chronic systemic disease characterized by metabolic
and vascular abnormalities
• A major clinical manifestation of disordered metabolism is hyperglycemia.
• Clinical manifestations of vascular disorders may include hypertension,
myocardial infarction, stroke, retinopathy, blindness, nephropathy, and
peripheral vascular disease.

4. Types of Diabetes Mellitus
• There are two types of Diabetes Mellitus- type 1 & 2
• Type 1 diabetes is a common chronic disorder of childhood which results
from an autoimmune disorder that destroys pancreatic beta cells.
• Type 2 is caused by decrease release and resistance of insulin.
• Insulin resistance means that higher-than usual concentrations of insulin are
required

5. Sign and Symptoms-Diabetes Mellitus
• Hyperglycemia
• Polydipsia- thirst
• Polyuria- urine
• Dehydration
• Polyphagia- appetite

6. EFFECTS OF INSULIN ON METABOLISM
• Insulin increases glucose transport into the liver, skeletal muscle, adipose
tissue, the heart, and some smooth muscle organs, such as the uterus.
• Insulin promotes transport of glucose into fat cells, where it is broken down
• When insulin is lacking, fat is released into the bloodstream as free fatty
acids.
• Blood concentrations of triglycerides, cholesterol, and phospholipids are also
increased

7. EFFECTS OF INSULIN ON METABOLISM
• Insulin increases the total amount of body protein by increasing transport
of amino acids into cells and synthesis of protein within the cells

8. Drugs Used For the Treatment of DM
Insulin:
• Exogenous insulin used to replace endogenous insulin
• Insulin and its analogs lower blood glucose levels by increasing glucose
uptake by body cells, especially skeletal muscle and fat cells
• Decreasing glucose production in the liver
• Insulin is the only effective treatment for type 1
• The only clear-cut contraindication to the use of insulin is hypoglycemia

9. Insulin and its types
• Human insulin means that the synthetic product is identical to endogenous
insulin
• Insulin cannot be given orally because it is a protein that is destroyed by
proteolytic enzymes in the GI tract.
• It is given only parenterally, most often SC
• Short acting, Intermediate acting or long acting.

10. Insulin and its types
• Short-acting insulins have a rapid onset and a short duration of action.
• Intermediate- and long-acting insulins (except for insulin glargine) are
modified by adding protamine (a large, insoluble protein), zinc, or both to
slow absorption and prolong drug action.
• Several mixtures of an intermediate- and a short-acting insulin are available
and commonly used

11. Short Acting Insulin
• Regular insulin
• Hypoglycemic drug of choice for diabetics experiencing acute or emergency
situations, diabetic ketoacidosis, hyperosmolar nonketotic coma, severe
infections or other illnesses, major surgery, and pregnancy
• Only insulin preparation that can be given IV

12. Intermediate-acting Insulins
• NPH
• Commonly used for long-term administration
• Modified by addition of protamine (a protein) and zinc
• Given only SC
•

13. Long-acting Insulin
• Ultralente
• Modified by addition of zinc and formation of large crystals, which are
slowly absorbed
• Given SC

14. Insulin Analogs
• Lispro, aspart and Glargine
• Lispro and aspart have faster onset and a shorter duration of action than
human regular insulin and given 15 minutes before meal
• Glargine is long acting
• All are given SC

15. Oral Hypoglycemic drugs
• Sulfonylureas- Glipizide, Glyburide and Glimepiride
• Alpha glucosidase inhibitors- Acarbose
• Biguanides- Metformin
• Glitazones- Pioglitazone and rosiglitazone
• Meglitinides- Nateglinide and repaglinide

16. Sulfonylureas
• Called as insulin secretogogues
• MOA: Stimulates release of insulin from beta cell of pancreas by blocking
ATP sensitive K channels resulting in depolarization Ca influx and insulin
exocytosis
• Reduce hepatic glucose production
• Increase peripheral insulin sensitivity

17. Sulfonylureas
• AE: Weight gain, hyper insulinemia, hypoglycemia
• Should be used with caution in renal impaired patients
• Glyburide can be used in pregnancy

18. Glinides
• Called insulin secrotogogues
• Stimulates insulin secretion by binding to distinct sites on beta cells closing
ATP sensitive K channels
• Rapid onset and short duration of action is main difference from
sulfonylureas
• Can not be used with sulfonylureas as hypoglycemia can occur
• Also called post prandial glucose regulators

19. Glinides
• AE: Hypoglycemia, weight gain
• Less chances as compared to sulfonylureas

20. Biguanides
• Called as insulin sensitizer
• Increases glucose uptake and use by target tissues there by decreasing insulin
resistance
• Do not promote release of insulin so no problem of hyperinsulinemia and
no hypoglycemia
• MOA: Decrease hepatic gluconeogenesis, Slows intestinal absorption of
sugars and improves peripheral glucose uptake and utilization

21. Biguanides
• AE: Mostly gastrointestinal, interfere with vit B12 absorption
• Contraindicated in renal impairment as it can cause lactic acidosis
• Also used in the treatment of PCOD by lowering insulin resistance it
promotes ovulation and possibly pregnancy

22. Thiazolidinediones (TZDs)
• Called as insulin sensitizers
• MOA: Agonist of Peroxisome proliferator activated receptor (PPAR).
• Activation of this receptor regulates transcription of several insulin
responsive genes resulting in increase insulin sensitivity in adipose tissue, liver
and skeletal muscles
• ADA recommends pioglitazone as second or third line drug for diabetes

23. Thiazolidinediones (TZDs)
• Rosiglitazone is less used due to cardiac problems
• Should be avoid in nursing mothers
• AE: Liver toxicity, Weight gain due to deposition of fat and fluid retention
• Osteopenia and fractures
• Also used in PCOD

24. Alpha glucosidase inhibitor
• Alpha glucosidase enzyme complex glucose into simpler form so it can
absorbed
• Results in lower postprandial glucose level
• AE: flatulence, diarrhea and abdominal cramping
• CI: Inflammatory bowel disease,colonic ulceration, intestinal obstruction

25. Principle of therapy
The goals of treatment are
• Maintain blood glucose at normal or near-normal levels
• Promote normal metabolism of carbohydrate, fat, and protein
• Prevent acute and long-term complications
• Prevent hypoglycemic episodes.

26. Principles of therapy
• Strict control of blood sugar delays the onset and slows progression of complications of diabetes
• Limited intake of dietary protein
• Prompt treatment of urinary tract infections
• Avoidance of nephrotoxic drugs when possible.