7.4 Antidiabetic Drugs

Antidiabetic Drugs
A. Alfia Muthmainnah T
Bagian Farmakologi FK Untad
2020
Introduction
Diabetes is a group of metabolic diseases characterized by
hyperglycemia resulting from defects in insulin secretion,
insulin action, or both
Diabetes can be classified into the following general

categories
• Type 1 diabetes
• Type 2 diabetes
• Gestational diabetes mellitus (GDM)
• Specific types of diabetes due to other causes
Pathogenesis
Pathogenesis
The Egregious Eleven

Diagnosis
Treatment: Insulin
• insulin is a small protein with a molecular weight in humans of
5808
• insulin is released from pancreatic beta cells at a low basal
rate
• response to a variety of stimuli, especially glucose, amino
acids, hormones such as glucagon-like polypeptide-1 (GLP-1),
glucose-dependent insulinotropic polypeptide (GIP), glucagon,
cholecystokinin, high concentrations of fatty acids, and β-
adrenergic sympathetic activity are recognized.
Treatment: Insulin
Treatment: Insulin
Anabolic action
↑ protein synthesis
↑ glycogen synthesis
↑ triglyceride storage
Treatment: Insulin
Insulin Delivery Systems

• Standard Delivery
• Portable Pen Injectors
• Continuous Subcutaneous Insulin Infusion Devices (CSII,
Insulin Pumps)
Treatment: Insulin
Treatment: Insulin
Types and Duration of Action of Insulin Preparations

Treatment: Insulin
Insulin diperlukan pada keadaan
• HbA1c > 9% dengan kondisi dekompensasi metabolik
• Penurunan berat badan yang cepat
• Hiperglikemia berat yang disertai ketosis
• Krisis Hiperglikemia
• Gagal dengan kombinasi OHO dosis optimal
• Stres berat (infeksi sistemik, operasi besar, infark miokard akut, stroke)
• Kehamilan dengan DM/Diabetes melitus gestasional yang tidak
terkendali dengan perencanaan makan
• Gangguan fungsi ginjal atau hati yang berat
• Kontraindikasi dan atau alergi terhadap OHO
• Kondisi perioperatif sesuai dengan indikasi
Treatment: Insulin
Complications
• Hypoglycemia
• Insulin allergy
• Lipodystrophy at Injection Sites
• Increased Cancer Risk
Treatment: Glucagon-like Polypeptide-1
(Glp-1) Receptor Agonists
the release of glucagon-like polypeptide is diminished
postprandially
synthetic analogs of glucagon-like polypeptide, exenatide and

liraglutide
actions
• potentiation of glucose mediated insulin secretion
• suppression of postprandial glucagon
• release through as-yet unknown mechanisms, slowed gastric
emptying,
• central loss of appetite
Treatment: Glucagon-like Polypeptide-1
(Glp-1) Receptor Agonists
PK
• Peak levels are obtained in 8–12 hours
• prolonged half-life
• injected subcutaneously within 60 minutes before a meal;
Decrease of HbA 1c from 0.8% to 1.5% & weight loss ranges

from nominal to 3.2 kg
side effects
• headache, nausea, and diarrhea; antibody formation,
urticaria, and other immune reactions
• also are observed hypoglycemia can occur with concomitant
sulfonylurea
• pancreatitis
Treatment
Treatment: Sulfonylureas
Mechanism of Action  SECRETAGOGUES
• increase insulin release from the pancreas
• reduction of serum glucagon levels
• closure of potassium channels in extrapancreatic tissue
FIRST-GENERATION
• Tolbutamide  is well absorbed but rapidly metabolized in the
liver. Its duration of effect is relatively short, with an elimination
half-life of 4–5 hours
• Chlorpropamide  half-life of 32 hours and is slowly
metabolizedapproximately 20–30% is excreted unchanged in the
urine. Contraindicated in patients with hepatic or renal
insufficiency.
• Tolazamide comparable to chlorpropamide in potency but has a
shorter duration of action, more slowly absorbed than the other
sulfonylureas, andhalf-life is about 7 hours
Treatment: Sulfonylureas
SECOND-GENERATION SULFONYLUREAS
• Glyburide is metabolized in the liver into products with very
low hypoglycemic activity, contraindicated in the presence of
hepatic impairment and in patients with renal insufficiency
• Glipizide has the shortest half-life (2–4 hours) of the more
potent agents, should be ingested 30 minutes before
breakfast, 90% of glipizide is metabolized in the liver to
inactive products, and 10% is excreted unchanged in the urine
• Glimepiride is approved for once-daily use as monotherapy or
in combination with insulin, has a long duration of effect with
a half-life of 5 hours
Treatment: Meglitinide
INSULIN SECRETAGOGUE: Repaglinide
• modulate betacell insulin release by regulating potassium
efflux through the potassium channels
PK
• very fast onset of action, with a peak concentration and
peak effect within approximately 1 hour after ingestion,
• duration of action is 4–7 hours
• Hepatically cleared by CYP3A4 with a plasma half-life of 1
hour.
• Because of its rapid onset, repaglinide is indicated for use
in controlling postprandial glucose excursions
Treatment: BIGUANIDES
Mechanisms of Action
• reduce hepatic glucose production through activation of the enzyme
AMP-activated protein kinase (AMPK)
PK
• half-life of 1.5–3 hours
• not bound to plasma proteins, not metabolized, and is excreted by
the kidneys as the active compound
AEs
• Gastrointestinal (anorexia, nausea, vomiting, abdominal discomfort,
and diarrhea)
• reduced Absorption of vitamin B 12
• risk of lactic acidosis
Treatment: Thiazolidinediones
Mechanisms of Action: pioglitazone
and rosiglitazone
• decrease insulin resistance
PK
• absorbed within 2 hours of ingestion; although food may delay uptake,

• total bioavailability is not affected.
• metabolized by CYP2C8 and CYP3A4 to active metabolites
AEs
• fluid retention which presents as a mild anemia and peripheral edema

• increase the risk of heart failure
Treatment: α-glucosidases inhibitor
Mechanisms of Action: Acarbose and miglitol

• competitive inhibitors of the intestinal α-glucosidases
and reduce postmeal glucose excursions by delaying
the digestion and absorption of starch and
disaccharides
AEs
• flatulence, diarrhea, and abdominal pain
• hypoglycemia may occur with concurrent sulfonylurea
treatment
Treatment: DPP-IV and SGLT-2 inhibitor
DPP-IV inhibitor
• inhibitors of DPP-4, the enzyme that
degrades incretin hormones
• e.q.:Sitagliptin, saxagliptin, and linagliptin
SGLT-2 inhibitor
• Inhibit reabsorbsi glucose in distal tubule 
inhibitor glucose transporter
• e.q.: canaglifozin, dapaglifozin
Treatment
Treatment

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Antidiabetic Drugs

Diabetes can be classified into the following general

The Egregious Eleven

Insulin Delivery Systems

Types and Duration of Action of Insulin Preparations

synthetic analogs of glucagon-like polypeptide, exenatide and

Decrease of HbA 1c from 0.8% to 1.5% & weight loss ranges

• absorbed within 2 hours of ingestion; although food may delay uptake,

• fluid retention which presents as a mild anemia and peripheral edema

Mechanisms of Action: Acarbose and miglitol

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