ORAL ANTIDIABETICS

Drugs That Primarily Stimulate Insulin Release by Binding to the Sulfonylurea Receptor

Drugs That Primarily Stimulate Insulin Release by Binding to the Sulfonylurea Receptor

Drugs That Primarily Lower Glucose Levels by Their Action on the Liver, Muscle and Adipose

Tissue

Drugs That Primarily Lower Glucose Levels by Their Action on the Liver, Muscle and Adipose

Tissue

Drugs That Affect Absoprtion of Glucose Drugs That Affect Absoprtion of Glucose Drugs That Mimic Incretin Effect or Prolong

Incretin Action

Drugs That Mimic Incretin Effect or Prolong Incretin Action

Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitors

Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitors

Other Hypoglycemic Drugs Other Hypoglycemic Drugs

Sulfonylureas, Meglitinide Analogs

Biguanides, Thiazolidinediones α-glucosidase inhibitors

GLP-1 agonists, DPP-4 inhibitors

Pramlintide, Colesevelam HCL, Bromocriptine

SGLT2 inhibitors

Subclass, Drug Mechanism of action Effects Clinical application Pharmacokinetics, Toxicities, Interactions SULFONILUREAS

• Glipizide

• Glyburide

• Glymepride

• Gliclazide

Insulin

secretagogues:

Close K

channels in beta cells

Increase insülin release

Reduce circulating glucose in patient with functioning beta cells

Type 2 Diabetes Orally active

• Duration 10-24 h

• Toxicity:

Hypoglycemia, weight gain

• Tolazamide, tolbutamide, chlorpropamide, acetohexamide: Older sulfonylureas, lower potency, greater

toxicity; rarely used

MEGLITINIDE ANALOGS; D-

PHENYLALANINE DERIVATIVE

• Repaglinide, nateglinide

• Mitiglinide

Insulin

secratagogue:

Similar to

sulfonylureas with some overlap in binding sited

In patients with functioning beta cells, reduce

circulating glucose

Type 2 Diabetes Oral

• Very fast onset of action

• Duration 5-8 h, nateglinide<4 h

• Toxicity:

Hypoglycemia

Subclass, Drug Mechanism of action Effects Clinical application Pharmacokinetics, Toxicities, Interactions BIGUANIDES

• Metformin Activates AMP kinase

Reduces hepatic and renal

gluconeogenesis

Decreases

circulating glucose Type 2 Diabetes Oral

• Maximal plasma concentration in 2-3 h

• Toxicity: GI symptoms, lactic acidosis (rare)

• Cannot use if impaired

rebal/hepatic function,

congestive heart failure (CHF), hypoxic/acidotic states,

alcoholism

ALPHA-

GLUCOSIDASE INHIBITORS

• Acarbose, miglitol

• Voglibose

Inhibit intestinal α-

glucosidases Reduce conversion of starch and

disaccharides to monosaccharides Reduce

postprandial hyperglycemia

Type 2 Diabetes Oral

• Rapid onset

• Toxicity; GI symptoms

• Cannot use if impaired

renal/hepatic function,

intestinal

disorders

Subclass, Drug Mechanism of

action Effects Clinical application Pharmacokinetics,

Toxicities, Interactions THIAZOLIDINEDIONS

• Poglitazone,

rosiglitazone Regulate gene expression by binding to PPAR- γ and PPAR-α

Reduce insülin

resistance Type 2 Diabetes Oral

• Long acting (> 24 h)

• Toxicity; Fluid retention, edema, anemia, weight gain, macular edema, bone fractures in women

• Cannot use if

CHF, hepatic

disease

GLP-1 RECEPTOR AGONISTS

• Exenatide, liraglutide, albiglutide, dulaglutide

Analog of GLP-1:

Binds to GLP-1 receptors

Reduce post meal glucose

excursions:

Increase glucose mediated insulin release, lower glucagon levels, slow gastric

emptying, decrease appetite

Type 2 Diabetes Parenteral (sc)

• Toxicity; Nausea, headache,

vomiting,

anorexia, mild

weight loss,

pancreatitis, C-

cell tumors in

rodents

Subclass, Drug Mechanism of action Effects Clinical application Pharmacokinetics, Toxicities, Interactions DPP-4 INHIBITORS

• Sitagliptin, saxagliptin, linagliptin, alogliptin, vildagliptin

Blocks degredation of GLP-1, raises circulating GLP-1 levels

Reduce post meal glucose

excursions:

Increase glucose mediated insulin release, lower glucagon levels, slow gastric

emptying, decrease appetite

Type 2 Diabetes Oral

• Half life ~ 12 h

• 24 h duration of action

• Toxicity:

Rhinitis, upper respiratory infections, headaches,

pancreatitis, rare

allergic reactions

♦ Canagliflozin

♦ Dapagliflozin

♦ Empagliflozin

Subclass, Drug Mechanism of action Effects Clinical application Pharmacokinetics, Toxicities, Interactions SGLT2 INHIBITORS

• Canagliflozin, dapagliflozin, empagliflozin

Block renal glucose

resoption Increase

glucosuria, lower plasma glucose levels

Type 2 Diabetes Oral

• Half life ~ 10-14 h

• Toxicity: Genital and urinary tract infections,

polyuria,

pruritus, thirst,

osmotic diuresis,

constipation

ISLET AMYLOID POLYPEPTIDE ANALOG

• Pramlintide Analog of amylin:

Binds to amylin receptors

Reduce post meal glucose

excursions: Lowers glucagon levels, slows gastric emptying,

decreases appetite

Type 1 and Type 2

Diabetes Parenteral (sc)

• Rapid onset

• Half life ~ 48 min

• Toxicity: Nausea, anorexia,

hypoglycemia,

headache

Subclass, Drug Mechanism of

action Effects Clinical application Pharmacokinetics,

Toxicities, Interactions BILE ACID

SEQUESTRANT

• Colesevelam

HCL Bile acid binder:

Lowers glucose through

unknown mechanism

Reduces glucose

levels Type 2 diabetes Oral

• 24 h duration of action

• Toxicity:

Constipation, indigestion, flatulence DOPAMINE

AGONIST

• Bromocriptine D

receptor

agonist: Lowers glucose through unknown

mechanism

Reduces glucose

levels Type 2 diabetes Oral

• 24 h action

• Toxicity:

Nausea,

vomiting,

dizziness,

headache

•Alogliptin (Nesina)

•Alogliptin and metformin (Kazano)

•Alogliptin and pioglitazone (Oseni)

•Linagliptin (Jentadueto)

•Linagliptin and metformin (Tradjenta)

•Saxagliptin (Ongylza)

•Saxagliptin and metformin (Kombiglyze)

•Sitagliptin (Januvia)

•Sitagliptin and metformin (Janumet)

GLUCAGON

• Increases gluconeogenesis

•Increases ketogenesis

•Increases catabolism of storage glycogen

•Potent inotropic-chronotropic effect on

heart (cAMP increase), similar effect to beta agonists

•High doses stimulate relaxation in the gut

Severe Hypoglycemia Severe Hypoglycemia

Endocrine Diagnosis Endocrine Diagnosis

Beta-Adrenoceptor Blocker Overdose Beta-Adrenoceptor

Blocker Overdose

Radiology of the Bowel

Radiology of the Bowel