MATERI KULIAH FARMAKOTERAPI 2

FAKULTAS FARMASI UNIVERSITAS HASANUDDIN

DIABETES MELLITUS

OLEH
USMAR
 Introduction
• Diabetes mellitus (DM) is a group of metabolic
disorders characterized by hyperglycemia.
• Associated with abnormalities in carbohydrate, fat,
and protein metabolism and results in chronic
complications including microvascular,
macrovascular, and neuropathic disorders.
• DM is the leading cause of blindness in adults aged
20 to 74 years, and the leading contributor to
development of endstage renal disease.
• Also accounts for approximately 71,000 lower
extremity amputations annually.
• A cardiovascular event is responsible for two-thirds
of deaths in individuals with type 2 DM.
 Introduction
• Optimal management of the patient with DM
will reduce or prevent complications, and
improve quality of life.
• Research and drug development efforts over
the past several decades have provided
valuable information that applies directly to
improving outcomes in patients with DM and
have expanded the therapeutic
armamentarium.
• Additionally, interventions in an attempt to
prevent complications and the onset of
diabetes have been reported for type 1 and 2
DM.
 Epidemiology
• Type 1 DM is an autoimmune disorder developing in childhood or early
adulthood, although some latent forms do occur.
• Type 1 DM idiopathic is a nonimmune form of diabetes frequently seen
in minorities, especially Africans and Asians, with intermittent insulin
requirements.
• Type 1 DM accounts for 5% to 10% of all cases of DM and is likely
initiated by the exposure of a genetically susceptible individual to an
environmental agent.
• Candidate genes and environmental factors are reportedly prevalent in
the general population, but development of β-cell autoimmunity occurs
in less than 10% of the genetically susceptible population and
progresses to type 1 DM in less than 1% of the population.
• The prevalence of -cell autoimmunity appears proportional to the
incidence of type 1 DM in various populations. For instance, the
countries of Sweden, Sardinia, and Finland have the highest prevalence
of islet cell antibody (3%–4.5%) and are associated with the highest
incidence of type 1 DM; 22 to 35 per 100,000.
• The prevalence of type 1 DM has been increasing over the last hundred
years, but the cause of the increase is not fully understood.6
 Epidemiology
• Markers of autoimmunity have been detected in 14%
to 33% of persons with type 2 DM in some
populations and manifest with early failure of oral
agents and insulin dependence. This type of DM has
also been referred to as latent autoimmune diabetes
in adults (LADA).
• Maturity onset diabetes of youth (MODY), which can
be due to one of at least six genetic defects, and
endocrine disorders such as acromegaly and Cushing
syndrome, can be secondary causes of DM. These
unusual etiologies, however, only account for 1% to
2% of the total cases of type 2 DM.
 Epidemiology
• The prevalence of type 2 DM is increasing.
• Multiple risk factors for the development of type 2 DM :
 family history (i.e., parents or siblings with diabetes);
 obesity (i.e., 20% over ideal body weight, or body mass index [BMI]
25 kg/m2);
 habitual physical inactivity;
 race or ethnicity ;
 impaired glucose tolerance, impaired fasting glucose, or HbAlc 5.7%–
6.4%;
 hypertension (140/90 mm Hg in adults);
 high-density lipoprotein (HDL) cholesterol 35 mg/dL and/or a
triglyceride level 250 mg/dL;
 history of gestational diabetes mellitus (GDM) or delivery of a baby
weighing >9 pounds;
 history of vascular disease;
 presence of acanthosis nigricans;
 polycystic ovary disease.
 Epidemiology
• The prevalence of type 2 DM increases with age, it is more
common in women than in men in the United States, and
varies widely among various racial and ethnic populations,
being especially increased in some groups of Native
Americans, Hispanic American, Asian American, African
American, and Pacific Island people.
• While the prevalence of type 2 DM increases with age, the
disorder is increasingly being recognized in adolescence.
• Much of the rise in adolescent type 2 DM is related to an
increase in adiposity and sedentary lifestyle, in addition to
an inheritable predisposition.
• Most cases of type 2 DM do not have a well-known cause;
therefore, it is uncertain whether it represents a few or
many independent disorders manifesting as
hyperglycemia.
Classification of Diabetes
 Treatment
The primary goals of DM management are
• to reduce the risk for microvascular and
macrovascular disease complications
• to ameliorate symptoms
• to reduce mortality,
• to improve quality of life
 Nonpharmacologic Therapy (1) - Diet
• Medical nutrition therapy is recommended for all persons with DM
• For individuals with type 1 DM, the focus is on regulating insulin
administration with a balanced diet to achieve and maintain a
healthy body weight.
• A meal plan that is moderate in carbohydrates and low in
saturated fat (<7% of total calories), with a focus on balanced
meals is recommended.
• Patients with type 2 DM often require caloric restriction to
promote weight loss, and portion size and frequency are often
issues.
• Rather than a set diabetic diet, advocate a diet using foods that
are within the financial reach and cultural milieu of the patient.
• As most patients with type 2 DM are overweight or obese,
bedtime and between-meal snacks are not needed if
pharmacologic management is appropriate.
 Nonpharmacologic Therapy (2) - Activity
• Most patients with DM can benefit from increased activity
• Aerobic exercise improves insulin sensitivity and glycemic control
in the majority of individuals, and reduces cardiovascular risk
factors, contributes to weight loss or maintenance, and improves
well-being.
• The patient should choose an activity that she or he is likely to
continue. Start exercise slowly in previously sedentary patients.
• In addition, several complications (uncontrolled hypertension,
autonomic neuropathy, insensate feet, and retinopathy) may
require restrictions on the activities recommended.
• Physical activity goals include at least 150 minutes/week of
moderate (50%–70% maximal heart rate) intensity exercise. In
addition, resistance training, in patients without retinal
contraindications, is recommended for 30 minutes 3 times/week.
 Pharmacologic Therapy

• Until 1995, only two options for pharmacologic

treatment were available for patients with
diabetes; sulfonylureas (for type 2 DM only)
and insulin (for type 1 or 2).
• Since 1995, a number of new oral agents,
injectables, and insulins have been introduced
in the United States.
 Pharmacologic Therapy
Currently, eight classes of oral agents are approved
for the treatment of type 2 diabetes:
1. α-glucosidase inhibitors
2. Biguanides
3. Meglitinides
4. peroxisome proliferator activated receptor
agonists (which are also commonly identified as
thiazolidinediones or glitazones)
5. dipeptidyl peptidase 4 (DPP-4) inhibitors
6. dopamine agonists
7. bile acid sequestrants
8. Sulfonylureas.
 Pharmacologic Therapy
Oral antidiabetic agents are often grouped
according to their glucose-lowering mechanism of
action.
Biguanides and thiazolidinediones are often
categorized as insulin sensitizers due to their
ability to reduce insulin resistance.
Sulfonylureas and meglitinides are often
categorized as insulin secretagogues because
they enhance endogenous insulin release.
 Pharmacologic Therapy

• Diabetes treatment options continue to evolve,

with newer oral agents and non-insulin
injectables potentially altering future algorithms
for the treatment of diabetes. The subsequent
sections describe the current antidiabetic
medications that are available to treat type 1 and
type 2 diabetes mellitus.