DRUGS

FOR DIABETES
By : Queenie B. Biang
BSN II A
 OVERVIEW

The pancreas produces the peptide hormones insulin,

glucagon, and somatostatin. The peptide hormones
are secreted from cells in the islets of Langerhans.
These hormones play an important role in regulating
metabolic activities of the body, particularly glucose
homeostasis. A relative or absolute lack of insulin, as
seen in diabetes mellitus, can cause serious
hyperglycemia. Left untreated, retinopathy,
nephropathy, neuropathy, and cardiovascular
complications may result.
 DIABETES MELLITUS
Diabetes is not a single disease. Rather, it is a
heterogeneous group of syndromes characterized by
elevated blood glucose attributed to a relative or
absolute deficiency of insulin. The American Diabetes
Association (ADA) recognizes four clinical
classifications of diabetes: type 1 diabetes, type 2
diabetes, gestational diabetes, and diabetes due to other
causes such as genetic defects or medications.
 WHAT ARE THE
DIFFERENT TYPES
OF DIABETES?
 Type Type
1 2
most commonly
accounts for greater
afflicts children,
than 90% of cases.
adolescents, or young
Type 2 diabetes is
adults, but some latent
influenced by genetic
forms occur later in
factors, aging, obesity,
life. The disease is
and peripheral insulin
characterized by an
resistance, rather than
absolute deficiency of
autoimmune
insulin
processes.
 INSULIN
is a polypeptide hormone consisting
of two peptide chains that are
connected by disulfide bonds. It is
synthesized as a precursor
(proinsulin) that undergoes
proteolytic cleavage to form insulin
and C-peptide, both of which are
secreted by the β cells of the
pancreas.
 INSULIN
Insulin secretion is regulated by
blood glucose levels, certain amino
acids, other hormones, and
autonomic mediators. Secretion is
most often triggered by increased
blood glucose, which is taken up by
the glucose transporter into the β
cells of the pancreas.
MECHANISM OF ACTION
• Exogenous insulin is administered to
replace absent insulin secretion in type
1 diabetes or to supplement
insufficient insulin secretion in type 2
diabetes.
PHARMACOKINETICS
• the amino acid sequence of human insulin produces insulins with different
pharmacokinetic properties. Insulin preparations vary primarily in their onset and
duration of activity. Dose, injection site, blood supply, temperature, and physical activity
can also affect the onset and duration of various insulin preparations. Because insulin is
a polypeptide, it is degraded in the gastrointestinal tract if taken orally. Therefore, it is
generally administered by subcutaneous injection, although an inhaled insulin
formulation is also available. [Note: In a hyperglycemic emergency, regular insulin is
administered intravenously (IV).
PHARMACOKINETICS
• Continuous subcutaneous insulin infusion (also called the
insulin pump) is another method of insulin delivery. This
method of administration may be more convenient for
some patients, eliminating multiple daily injections of
insulin. The pump is programmed to deliver a basal rate of
insulin. In addition, it allows the patient to deliver a bolus
of insulin to cover mealtime carbohydrate intake and
compensate for high blood glucose.
ADVERSE EFFECT
• Hypoglycemia is the most serious
and common adverse reaction to
insulin
• weight gain, local injection site
reactions, and lipodystrophy
 INSULIN
PREPARATIONS
AND TREATMENT
 Insulin preparations are classified as rapid-, short-,
intermediate-, or long-acting.
summarizes onset of action, timing of peak level, and
duration of action for the various types of insulin. It is
important that clinicians exercise caution when
adjusting insulin treatment, paying strict attention to
the dose and type of insulin.
 RAPID-ACTING
AND SHORT-
ACTING INSULIN
PREPARATIONS
Intermediate-Acting Insulin
Long-Acting Insulin Preparations
 STANDARD TREATMENT
VERSUS INTENSIVE
TREATMENT
Standard Insulin therapy involves twice daily injections.
In contrast, Intensive Treatment utilizes three or more
injections daily with frequent monitoring of blood
glucose levels. intensive therapy show a significant
reduction in microvascular complications of diabetes
such as retinopathy, nephropathy, and neuropathy
compared to patients receiving standard care
 SYNTHETIC AMYLIN
ANALOG
Amylin is a hormone that is cosecreted with insulin from β cells following food intake.
It delays gastric emptying, decreases postprandial glucagon secretion, and improves
satiety. Pramlintide is a synthetic amylin analog that is indicated as an adjunct to
mealtime insulin therapy in patients with type 1 and type 2 diabetes. Pramlintide is
administered by subcutaneous injection immediately before meals. When pramlintide is
initiated, the dose of mealtime insulin should be decreased by 50% to avoid a risk of
severe hypoglycemia. Other adverse effects include nausea, anorexia, and vomiting.
Pramlintide may not be mixed in the same syringe with insulin, and it should be
avoided in patients with diabetic gastroparesis (delayed stomach emptying), cresol
hypersensitivity, or hypoglycemic unawareness.
 GLUCAGON-LIKE
PEPTIDE RECEPTOR
AGONISTS
Oral intake of glucose results in a higher secretion of insulin than
occurs when an equal load of glucose is given IV. This effect is
referred to as the "incretin effect and is markedly reduced in type 2
diabetes. . lncretin hormones are responsible for 60% to 70% of
postprandial insulin secretion. Albiglutide, dulaglutide, exenatide ,
liraglutide , lixisenatide and semaglutide are injectable GLP-1
receptor agonists used for the treatment of type 2 diabetes.
Liraglutide is also approved to reduce the risk of cardiovascular
events and cardiovascular mortality in patients with type 2 diabetes
and cardiovascular disease
 MECHANISM OF ACTION

These agents are analogs of GLP-1 that exert their

activity by improving glucose-dependent insulin
secretion, slowing gastric emptying time, reducing
food intake by enhancing satiety (a feeling of fullness),
decreasing postprandial glucagon secretion, and
promoting β cell proliferation.
 PHARMACOKINETICS

GLP-1 receptor agonists are administered

subcutaneously, since they are polypeptides.
Albiglutide, dulaglutide, liraglutide, and semaglutide
are considered long-acting GLP-1 receptor agonist
 ADVERSE EFFECTS

The main adverse effects of the incretin mimetics

consist of nausea, vomiting, diarrhea, and constipation.
GLP-1 receptor agonists have been associated with
pancreatitis and should be avoided in patients with
chronic pancreatitis.
 ORAL
AGENTS
Oral Agents are useful in the treatment of patients who
have type 2 diabetes that is not controlled with diet.
Patients who developed diabetes after age 40 and have
had diabetes less than 5 years are most likely to
respond well to oral glucose-lowering agents
 SULFONYLUREAS
These agents are classified as insulin secretagogues,
because they promote insulin release from the β cells
of the pancreas. Used in clinical practice are the
second-generation drugs glyburide , glipizide and
glimepiride.
Mechanism Of Action Pharmacokinetics Adverse effects

These agents stimulate Given orally, these drugs

insulin release from the β bind to serum proteins, Adverse effects of the
cells of the pancreas. are metabolized by the sulfonylureas include
Blocks ATP-sensitive K+ liver, and are excreted in hypoglycemia,
channels, resulting in the urine and feces. The hyperinsulinemia, and
depolarization, Ca2+ duration of action ranges weight gain
influx, and insulin from 12 to 24 hours.
exocytosis
 GLINIDES

This class of agents includes repaglinide and

nateglinide. Glinides are also considered insulin
secretagogues.
Mechanism Of Action Pharmacokinetics Adverse effects

have a rapid onset and a

Glinides should be taken
short duration of action. hypoglycemia and
prior to a meal and are
They are particularly
well absorbed after oral weight gain. The
effective in the early
administration. Both incidence is lower
release of insulin that
occurs after a meal and glinides are metabolized than that with
are categorized as to inactive products by sulfonylureas.
postprandial glucose cytochrome
regulators.
 BIGUANIDES

Metformin , the only biguanide, is classified as an

insulin sensitizer. It increases glucose uptake and use
by target tissues, thereby decreasing insulin resistance.
Mechanism Of Action Pharmacokinetics Adverse effects

Metformin is well These are largely

absorbed after oral gastrointestinal, including
administration, is not diarrhea, nausea, and
reduction of hepatic vomiting. These effects can
bound to serum proteins,
gluconeogenesis. be alleviated by titrating the
and is not metabolized.
dose of metformin slowly
Excretion is via the and administering doses
urine. with meals. Metformin is
contraindicated in renal
dysfunction due to the risk
of lactic acidosis.
 THIAZOLIDINEDIONES

The thiazolidinediones are also insulin sensitizers. The

two agents in this class are pioglitazone and
rosiglitazone. Although insulin is required for their
action
Mechanism Of Action Pharmacokinetics Adverse effects

expand adipose tissue Liver toxicity has

Pioglitazone and occasionally been reported
mass via the maturation of
rosiglitazone are well with these drugs, and
preadipocytes into mature
absorbed after oral baseline and periodic
adipocytes and increase monitoring of liver function
administration and are
fat storage by increasing is recommended. Weight
extensively bound to
free fatty acid movement gain can occur because TZDs
serum albumin
into cells. may increase subcutaneous
fat and cause fluid retention.
These drugs should be
avoided in patients with
severe heart failure.
A-GLUCOSIDASE INHIBITORS

Acarbose and Miglitol are oral agents used for the

treatment of type 2 diabetes.
Mechanism Of Action Pharmacokinetics Adverse effects

Acarbose and miglitol Acarbose is poorly

The most common adverse
reversibly inhibit a- absorbed. lt is metabolized
effects are flatulence,
glucosidase enzymes. When primarily by intestinal diarrhea, and abdominal
taken at the start of a meal, bacteria, and some of the cramping. Adverse effects
these drugs delay the digestion metabolites are absorbed limit the use of these agents
of carbohydrates, resulting in and excreted into the urine. in clinical practice. Patients
lower postprandial glucose Miglitol is very well with inflammatory bowel
levels. Since they do not absorbed but has no disease, colonic ulceration,
stimulate insulin release or systemic effects. It is or intestinal obstruction
increase insulin sensitivity,
excreted unchanged by the should not use these drugs
these agents do not cause
kidney.
hypoglycemia when used as
monotherapy.
DIPEPTIDYL PEPTIDASE-4 INHIBITORS

Alogliptin, linagliptin , saxagliptin and sitagliptin are

oral dipeptidyl peptidase-4 {DPP-4) inhibitors used for
the treatment of type 2 diabetes.
Mechanism Of Action Pharmacokinetics Adverse effects

most common adverse effects

The DPP-4 inhibitors are well being nasopharyngitis and
absorbed after oral administration. headache. Although infrequent,
These drugs inhibit the
Food does not affect the extent of pancreatitis has occurred with
enzyme DPP4, which is absorption. Alogliptin and
responsible for the the use of DPP-4 inhibitors.
sitagliptin are mostly excreted
Agents in this dass may also
inactivation of incretin unchanged in the urine. The primary
increase the risk of severe,
hormones such as GLP-1 route of elimination for saxagliptin
and the metabolite is renal. disabling joint pain. Alogliptin
Linagliptin is primarily eliminated and saxagliptin have also been
via the enterohepatic system. All shown to increase the risk of
DPP-4 inhibitors except linagliptin heart failure hospitalizations and
require dosage adjustments in renal should be used with caution in
dysfunction. patients with or at risk for heart
failure.
 SODIUM-GLUCOSE
COTRANSPORTER 2 INHIBITORS

Canagliflozin, Dapagliflozin, Empagliflozin , and

Ertugliflozin are oral agents for the treatment of type 2
diabetes. Empagliflozin is also indicated to reduce the
risk of cardiovascular death in patients with type 2
diabetes and cardiovascular disease.
Mechanism Of Action Pharmacokinetics Adverse effects

Is responsible for reabsorbing These agents are given once

filtered glucose in the tubular daily in the morning.
common adverse effects with
lumen of the kidney. These Canagliflozin should be
SGLT2 inhibitors are female
agents decrease reabsorption taken before the first meal
genital mycotic infections
of glucose, increase urinary of the day. All drugs are
(for example, vulvo vaginal
glucose excretion, and lower mainly metabolized by candidiasis), urinary tract
blood glucose, may reduce glucuronidation to inactive infections,
systolic blood pressure. metabolites. These agents
However, they are not should be avoided in
indicated for the treatment of
patients with renal
hypertension.
dysfunction.
THANK YOU!