Professional Documents
Culture Documents
Medical Education-
Damietta University
Level 2
Semester 3
Module 1A
Drug therapy
for
diabetes mellitus
Mohamad-Hesham Daba
Mohamad-Hesham Daba
Prof. of clinical pharmacology
• Contact: clinical pharmacology Department.
• Official email: mhdaba@du.edu.eg
• Mobile (optional): 01119950988
• Academic hours:
Sunday day: 11:00-12:00 AM
Wednesday day: 11:00-12:00 AM
Learning Outcomes
By the end of the 3 lecture, the students will be able to:
1. List different insulin preparations
2. Describe the mechanism of action of insulin
3. Select appropriate dosage forms in clinical situations
4. Recognize side effects of insulin
5. Describe the mechanism of action and side effects of sulphonylureas,
metformin, acarbose, glitazones
6. Recognize side effects of sulphonylureas, metformin, acarbose,
glitazones
7. Describe newer antidiabetic drugs.
Case scenario, Clinical Correlate, Practice points
A 16-year-old boy working at Pizza shop presents with a history of
polyuria, polydipsia, and weight loss of 6 kg over 2 months.
His biochemical evaluation shows fasting plasma glucose –280 mg/dl,
postprandial plasma glucose – 380 mg/dl and HbA1c 8.5 %.
How would you manage?
Diabetes mellitus
• Definition of DM: It is a clinical syndrome
• Manifestations: Polyuria, polydipsia, polyphagia.
• Complications: neuropathy, retinopathy, nephropathy, DKA……….
• Laboratory investigations:
1. Urine analysis:
2. Blood glucose: fasting and 2-hrs postprandial.
3. Glycated hemoglobin (HbA1C): Indicates average blood sugar level
for the past 2-3 months
Normal Prediabetes DM
# patients,
in millions
15
0
total type 1 type 2
• Type 1 diabetes:
can develop at any age, but occurs most frequently in children and
adolescents.
• Type 2 diabetes:
is more common in adults and accounts for around 90% of all diabetes
cases.
• Gestational diabetes (GDM):
is a type of diabetes that consists of high blood glucose during
pregnancy and is associated with complications to both mother
and child.
Lines of treatment:
1. Diet control.
Insulin, U/ml
100
Glucose, mg/dl
80 80
60
40
20
Basal
Minutes 0 30 60 90 120
Sources of insulin:
Traditional (animal) insulin:
Human insulin:
- Identical to human insulin
- Prepared by recombinant DNA technology.
- Less antigenic & rare development of insulin resistance.
Insulin analogs:
- Few a.a. of the human insulin are switched or replaced
- The different molecule have different pharmacokinetic properties.
Insulin preparations:
Generic
Category Features Onset Peak Duration
names
(1)
Rapid acting
insulin analogs (1) insulin lispro
Given just before 0-15
(2) insulin aspart 1-2 h. 3-5 h.
meal min
Generic
Category Features Onset Peak Duration
names
(3) Made by
Intermediate Isophane insulin adding
acting (N.P.H.) protamine to
Insulin: insulin to 1-2 h. 4-6 h. 12-16 h.
increase the
duration of
action
Category Generic name Features Onset Peak Duration
(5)
Premixed Humalin 70/30 Rapid onset
Insulin (NPH/Reg.) (mixtard) <30 12-16 h.
(Biphasic) Long duration min
Mechanism of action of insulin:
Indications of insulin:
Type 1 DM.
Type 2 DM in some conditions:
After failure of oral drugs.
“stress conditions” e.g. infections, surgery,
or pregnancy.
Diabetic ketoacidosis (DKA):
regular insulin is the only type used i.v.
Insulin administration:
• All insulins are given by s.c.
injection.
• Regular insulin is the only type
that can be given i.v. in diabetic
emergencies.
• The standard insulin
concentration is 100 units/mL.
• It should be injected with a
standard U-100 syringe.
Insulin requirement
• A total daily dose of 0.4
units/kg/d is given initially
to a newly diagnosed
patient.
2 - Hepatotoxicity.
3 - Teratogenicity.
4 - Hypersensitivity reactions.
Glinides: repaglinide & nateglinide
• They increase insulin secretion
by the same mechanism like sulfonylureas .
• Adverse effects:
Hepatotoxicity
Salt and water retention leading to:
peripheral edema & weight gain.
(avoid in patients with CHF).
α-Glucosidase inhibitors: Acarbose
• They act by competitive
inhibition of intestinal α-
glucosidase enzyme → ↓
digestion & absorption of
carbohydrates. (starch blockers)
• GIT side effects are common:
Flatulence, diarrhea, abdominal
pain.
Case Discussion/reflection
• According to the current recommendation of professional guidelines, the patient
should be prescribed metformin therapy concurrently with dietary and lifestyle
measures. This is based on the finding that metformin can delay progression of
diabetes and prevent microvascular as well as macrovascular (heart attack,
stroke) complications. Metformin does not increase circulating insulin, reduces
insulin resistance, is unlikely to induce hypoglycaemia and may have a positive
influence on pancreatic p cell health. Lack of serious toxicity over several decades
of use of metformin is well established. No other antidiabetic drug has all these
favourable features, and therefore, it is considered the first-choice drug.
Metformin is particularly suitable for this patient who is overweight, because it
can help weight reduction. A combination of antidiabetic drugs is not indicated at
this stage. Another drug needs to be added only when the target blood glucose
and HbA1 , levels are not attained by metformin alone.
Q1
Dulaglutide:
• is a very long acting GLP-1 receptor agonists which need to be
injected once weekly.
Dipeptidyl peptidase 4 inhibitors (Gliptins):
Sitagliptin
Mechanism of action:
inhibits dipeptidyl peptidase 4 (DPP-4),
the enzyme responsible for the proteolysis of the incretins (GLP-1).
Therapeutic uses:
Type 2 DM: given orally
Used alone or in combination with metformin.
Side effects:
headache and nausea.
Sodium-glucose cotransporter-2 (SGLT2) inhibitors
• Treatment:
1. If the patient is conscious or semiconscious → give him sugar solution.
2. If the patient is in deep coma:
(1) i.v. glucose
(2) Glucagon i.m.
Treatment of diabetic ketoacidosis
• Fluids:
isotonic saline solution i.v. immediately.
• Regular insulin:
i.v infusion (0.1 unit/kg/hr). switch to s.c. insulin
when the patient is biochemically stable.
• Potassium: is given according to K+ level.
• Bicarbonate (HCO3): only in severe acidosis.
• Treatment of precipitating factors e.g. antibiotics for infection.
Q1. Sitagliptin acts by:
a) Reducing the absorption of carbohydrate from the gut
b) Increasing the uptake of glucose in peripheral tissues
c) Reducing the hepatic gluconeogenesis
d) Inhibits dipeptidyl peptidase 4 (DPP-4)
Q2. One the main advantages of Liraglutide over exenatide is that
A. It longer in duration.
B. It is a synthetic amylin analogue.
C. It increases glucagon secretion.
D. It is used instead of insulin in type 1 diabetes
Q3. Dapagliflusin acts by:
a) Reducing the absorption of carbohydrate from the gut
b) Inhibits sodium-glucose cotransporter-2 (SGLT2)
c) Reducing the hepatic gluconeogenesis
d) Inhibits dipeptidyl peptidase 4 (DPP-4)
Q4. What is the first step in the management of diabetic
ketoacidosis?
a. To provide fluids intravenously
b. To provide insulin
c. To provide bicarbonate
d. To initiate insulin and fluids simultaneously
Q5. In a patient with type 2 diabetes, which drug mimics the action of
incretins to augment glucose-dependent insulin secretion?
(A) Acarbose
(B) Glucagon
(C) Exenatide
(D) Metformin
Nice to know
Amylin analogue: Pramlintide
• Amylin is produced by pancreatic beta cells and is stored in the same
granules as insulin. As such it is secreted along with insulin. acts in the
brain to reduce glucagon secretion from alpha cells.
• Pramlintide is a synthetic amylin analogue which is used to with
insulin injection when insulin alone fails to control postprandial
glycemic peak.
• Hypo glycaemia is the most important adverse effect.
Q4. Pramlintide is
A. a synthetic amylin analogue
B. a synthetic GLP-1 analogue
C. Sodium-glucose cotransporter-2 (SGLT2) inhibitor
D. An Alpha-glucosidase inhibitor
GLUCAGON
• It is secreted by the alpha cells of the islets of Langerhans and
commercially produced now by recombinant DNA technology.
• Uses
I. Hypoglycaemia Use of glucagon to counteract insulin/ oral
hypoglycaemic drug induced hypoglycaemia is only an appropriate
measure for the emergency, and must be followed by oral
glucose/sugar given repeatedly till the blood glucose level
stabilizes.
II. Glucagon may be used to stimulate the heart in beta adrenergic
blocker treated patients.
Simplified flow chart of management approaches in
diabetes mellitus (nice to know)
References or further readings