TREATMENT OF

DIABETES MELLITUS
BY: SHEWANI CHAWLA
IRFANULLAH SOLANGI
 Diabetes Mellitus:
• It is a clinical syndrome characterized by an increase in
plasma blood glucose (hyperglycaemia).

Types:
Type-1 DM
Type-2 DM
Gestational DM
Management Of Diabetes
For new cases of Diabetes, adequate glycaemic control can be
obtained by diet and lifestyle modifications alone in almost
50%; however 20-30% will need oral hypoglycaemic drugs and
rest 20-30% will require insulin.

The treatment of choice is determined by the capacity of the

residual B-cell function.
Diet and Lifestyle
• Lifestyle changes such as undertaking regular physical activity,
taking a healthy diet and reducing alcohol consumption play a
very important role in improving glycaemic control, although
many people esp. the middle-aged and elderly find them difficult
to sustain.
Eating Healthy
• Carbohydrates:
Both the amount and source of carbohydrate affect post-
prandial glucose.
Consumption of foods with a low GI is encouraged because
they produce a slow, gradual rise in blood glucose.
e.g. starchy foods as basmati rice, spaghetti, beans and lentils.
Weight Management & Exercise
• Obesity, particularly central obesity with increased waist circumference
predicts insulin resistance and cardiovascular risk.
The diabetic patients should be counselled to achieve a regular physical
activity as; walking, swimming, cycling or gardening.
Alcohol:
Beneficial as well as harmful
Should be taken in moderation
High in calorie content
Supresses gluconeogenesis increases hypoglycaemia
 Hypoglycaemic Drugs
1) Biguanides
• Metformin is the only biguanide available now.
Indications:
Used as first line therapy for Type-2 diabetes irrespective of weight.
Used in combination with insulin in obese patients with Type-1 diabetes.
Mechanism Of Action:
Acts as insulin sensitizer
Reduces hepatic glucose production
Increases peripheral glucose uptake
Impairs gut glucose uptake
Clinical Use:
• Metformin is a weight-neutral, potent glucose lowering drug.
It does not cause hypoglycaemia.
Effective in microvascular disease.
Dose: Started at low dose (500mg BD daily)
Maintenance dose: 1g BD daily
Side effects: GI upset and increased susceptibility to lactic acidosis.
Contraindications: Renal Failure
Impaired Hepatic function
Excessive Alcohol Intake
 2) Sulfonylureas
• These agents are classified as insulin secretagogues because they promote
insulin release from pancreatic B-cells.
Commonly used drugs are Glyburide (glibenclamide), Glipizide and
Glimepiride.

Mechanism Of Action
Sulfonylureas block the ATP-sensitive K+ channels resulting in
depolarization, Ca+ influx and insulin exocytosis.
Clinical Use:
• Sulfonylureas are an effective therapy for lowering blood glucose.
Often used as an add-on to metformin
Effective for microvascular complications.
Dose: 0.5mg at starting.
Adverse Effects: Weight gain and hypoglycaemia.
They should be used with caution in hepatic or renal insufficiency.
 3) Glinides
• Glinides are also considered insulin secretagogues.
Agents used are: Repaglinide and Nateglinide.

They are sulfonylurea like drugs although short acting.

The incidence to cause weight gain and hypoglycaemia is lower than that
with the sulfonylureas.
Glinides should not be used in combination with sulfonylureas due to
overlapping mechanisms of action.
 4) Alpha-glucosidase inhibitors
• Acarbose and Miglitol are the oral agents.

They inhibit the disaccharidases and delay the digestion of carbohydrates

resulting in lower postprandial glucose levels.
These agents do not cause hypoglycaemia when used as monotherapy.
They can be combined with sulphonylurea.

Adverse effects: Flatulence, Diarrhoea, Abdominal bloating.

 5) Thiazolidinediones
• Also called as TZD’s, glitazones or insulin sensitizers

TZD’s lower insulin resistance by acting as PPAR , a nuclear hormone

receptor.
Members of this class are Rosiglitazone and Pioglitazone.
Rosiglitazone increases the risk for MI and so is withdrawn now.
Pioglitazone is effective at lowering blood glucose esp. in insulin-resistant
patients.
Often given with metformin, may be given with insulin therapy.
Adverse effects: Weight gain and fluid retention.
 6) Incretin-based therapies
DPP-inhibitors & GLP-1 analogues
• Oral glucose results in a higher secretion of insulin than occurs when an
equal load of glucose is given IV, this is called “incretin effect”.
This effect occurs because gut release incretin hormones and it is
markedly reduced in type 2 diabetes.
The DPP-4 inhibitors or gliptins inhibit the enzyme DPP-4.
The class of agents includes Sitagliptin, Saxagliptin, Vildagliptin and
Linagliptin.
These agents are well-tolerated and weight neutral.
 GLP-1 analogues (incretin mimetics)
• Currently available GLP-1 analogues are Exenatide, Exenatide MR and
Liraglutide.
These agents are not orally active and are given by S/C injections.
Mechanism Of Action:
They exert their activities by acting as GLP-1 receptor agonists.
These agents delay gastric emptying, reduces food intake by enhancing
satiety and decreases postprandial glucagon secretion.
GLP-1 agonists lower blood glucose and result in weight loss, a desirable
therapy.
Therapeutic Goals in DM Type 1
The primary therapy in Diabetes Type 1 is Insulin therapy.
There are four basic forms of Insulin
1. Rapid Acting
2. Short Acting
3. Intermediate Acting
4. Long Acting
 SGLT2 inhibitors
• The sodium-glucose cotransporter 2 is responsible for reabsorption of
filtered glucose in kidney. Inhibition of SGLT2 increases the glucose
excretion and lowers blood glucose.
Drugs are Canagliflozin and Dapagliflozin.
Stepwise Management
 Rapid Acting Insulin
Type Onset Peak Duration

Insulin Lipsro
(Humanlog) 15-30min 1-2 3-5

Insulin Aspart
(Novolog) 15-30min 1-2 3-5
 Short Acting Insulin

Type Onset Peak Duration

Regular Insulin
0.5-1 h 2-3 3-6h
 Intermediate Acting

Type Onset Peak Duration

NPH 2-4 4-6 8-12

Lente 3-4 6-12 12-18

 Long Acting Insulin

Type Onset Peak Duration

Glargine 4-5 Peak less 22-24

Permanent Treatment of DM
• Early attempts at the transplantation of pancreatic cells have largely
failed, mostly due to immune reactions against donor cells that cause
destruction of implanted cells.
• The most advanced alternative comes from the Diabetic Research
Institute in US, in which a bioengineered mini-organ where insulin-
producing cells are encapsulated within a protective barrier.
ERCP (Endoscopic Retrograde
Cholangiopancreatography)
Present Scenario of Diabetes Mellitus
• The statistics of 2012 shows that violence killed 620,000
people. 800,000 people committed suicide but diabetes
has killed 1.5 million people singly!!
• The WHO report of 2016 says that 1.6 million deaths
directly caused by diabetes mellitus.
• By 2030, it is estimated that half of the world population
would be obese which is the number one risk factor of
diabetes mellitus.
THANKYOU!