Pharmacology related to diabetes mellitus. Insulin & other hypoglycemic medicines. Diabetes Mellitus type 1 & type 2 insulin dependent & non insulin dependent diabetes.

1. Diabetes
Mellitus
Dr.
Naveed
Khalid

2. Diabetes comes from a Greek word
meaning ‘to pass or flow through’ (i.e.
excessive urination) and mellitus means
‘sweet’. It is a disease caused by a relative
or absolute deficiency of insulin.
There are two main types of diabetes

3.  Type 1 is also known as juvenile onset diabetes or
insulin dependent diabetes mellitus (IDDM).
 • Loss of pancreatic B cells
 Type 2 is also known as maturity onset diabetes or
non-insulin dependent diabetes mellitus (NIDDM).
 Decreased response to insulin
 Type 1 has an autoimmune causation which is also
responsible for a late-onset form known as late
onset autoimmune diabetes in adults (LADA).

5. Clinical features
The classic symptoms of uncontrolled diabetes are:
 Polyuria
 Polydipsia
 Loss of weight (type 1)
 Tiredness and fatigue
 Propensity for infections, especially of the skin and
genitals (vaginal thrush)
 The young person with type 1 diabetes typically
presents with a brief 2–10 week history of the
classic triad of symptoms:
DxT : thirst + polyuria + weight loss → type 1 diabetes

6. Insulin

14. Insulin regimens
for type 1 diabetes
The most commonly used insulin injection
preparations are the ‘artificial’ human insulins.
Insulins are classified according to their time
course of action:
 rapid-acting and short duration (ultra-short)—
 insulin lispro, insulin aspart
 short-acting—
 neutral (regular, soluble)

15.  intermediate-acting—
 isophane (NPH) or lente
 long-acting—
 ultralente, insulin detemir, insulin
glargine
 pre-mixed short/intermediate—
 biphasic (neutral + isophane)
Insulin regimens
for type 1 diabetes

22. Methods of giving insulin injections
When
Suggest the patient develops a set routine, such as eating
meals on time and giving the injection about 30 minutes
before the meal.
Where
Into subcutaneous tissue—the best place is the abdomen.
The leg is also acceptable. It is advisable to keep to one
area (usually abdomen) and avoid injections into the arms,
near joints and the groin. The injection should be given at a
different place each time, at least 3 cm from the previous
injection. This reduces the risk of the development of
lipodystrophy. The means of delivery is the insulin syringe or
the insulin delivery pen.
1.

23. Methods of giving insulin injections
How
Pinch a large area of skin on the abdomen between
the thumb and fingers and insert the needle.
Guidelines for the patient
Take your insulin every day, even if you feel ill.
Do not change your dose unless instructed by your
doctor or you are competent to do so yourself.

24. Type 2 diabetes:
First-line treatment (especially if obese)
 Diet therapy
 Exercise program
 Weight loss

25. Biguanides
(Increase insulin sensitivity)
● Drug: Metformin
● Mechanism: involve ↑ tissue sensitivity to insulin and/or
↓ hepatic gluconeogenesis
● Side Effects: GI upset, lactic acidosis (use with caution in
renal insufficiency), vitamin B12 deficiency. Weight loss
(often desired).
● “Euglycemic,” ↓ postprandial glucose levels, but does not
cause hypoglycemia or weight gain

26. Thiazolidinediones
(Increase insulin sensitivity)
● Drugs: Pioglitazone and Rosiglitazone
● Mechanism: bind to nuclear peroxisome
proliferator-activating receptors (PPARγ) involved in
transcription of insulin-responsive genes →
sensitization of tissues to insulin, plus ↓ hepatic
gluconeogenesis and triglycerides and ↑ insulin
receptor numbers.
● Side effects: less hypoglycemia than sulfonylureas,
weight gain, edema, HF

27. Sulfonylureas (Increase insulin
secretion)
● Sulfonylureas (1st gen): Chlorpropamide, tolbutamide
● Sulfonylureas (2nd gen): Glipizide, glyburide
● Mechanism: Close K+ channels in pancreatic B cell
membrane  Ž
cell depolarizes  Ž
insulin release via •
Ca2+ influx.
● Side Effects: Hypoglycemia, Weight gain, Drug
interactions mainly with first-generation drugs

28. GLP-1 analogs (Increase glucose-
induced insulin secretion)
● Drugs: Exenatide, liraglutide
● Mechanism: •
GLP-1 is an incretin released from the
small intestine. It augments glucose-dependent insulin
secretion.
● ↓ glucagon release, 
↓ gastric emptying, •
↑ glucose-
dependent insulin release.
● Parenteral administration
● Adverse Effects: Nausea, vomiting, pancreatitis.
● Weight loss (often desired), satiety (often desired).

29. DPP-4 inhibitors (Increase glucose-
induced insulin secretion)
● Drugs: “-glips” Linagliptin, saxagliptin, sitagliptin
● Mechanism: Inhibit DPP-4 (dipeptidyl peptidase-4)
enzyme that deactivates GLP-1.
↓ glucagon release, 
↓ gastric emptying. 
↑ glucose-dependent insulin
release.
● Oral administration
● Side effects: Respiratory and urinary infections,
weight neutral, satiety (often desired).

30. Sodium-glucose Cotransporter 2
inhibitors (SGLT-2)
(Decrease glucose absorption)
● Drugs: “-glifs” Canagliflozin, dapagliflozin, empagliflozin
● Mechanism: Block reabsorption of glucose in proximal
convoluted tubule.
● Oral
● Adverse Effects: Glucosuria (UTIs, vulvovaginal
candidiasis), dehydration (orthostatic hypotension), weight
loss.
● Use with caution in renal insufficiency (
↓ efficacy with ↓
GFR).

31. α-glucosidase inhibitors
(Decrease glucose absorption)
● Drugs: Acarbose, miglitol
● Mechanism: Inhibit intestinal brush-border α-
glucosidases Ž
 delayed carbohydrate hydrolysis and
glucose absorption  Ž
• ↓ postprandial hyperglycemia.
● Oral administration
● Adverse Effects: GI upset, bloating.
● Not recommended in renal insufficiency.

32. Amylin analogs
● Drugs: Pramlintide
● Mechanism: •
Analog of amylin activates amylin
receptors. ↓ glucagon release, •
↓ gastric emptying.
● Parenteral administration
● Adverse Effects: Hypoglycemia, nausea, •
satiety
(often desired).