Medication used in Diabetes Mellitus (Part 2)

ORAL HYPOGLYCEMIC AGENTS

• Alpha-glucosidase inhibitors
• Insulin Secretagogues o Carbohydrate analogs that act as competitive
o Sulfonylureas inhibitors within the intestine for alpha-
▪ Increase insulin release from pancreas, glucosidase
reduce serum glucagon level (in long o Polysaccharides broken down by the
term use) glucosidase take longer to be broken down,
▪ Closure of potassium channels in reducing absorption rate of glucose
extrapancreatic tissue and pancreatic B
cell membrane, opening calcium • GLP1 agonists
channel and triggers insulin release o Potentiates glucose-mediated insulin secretion
o Meglitinides o Slows gastric emptying time and facilitates
central loss of appetite (sometimes utilized for
• Biguanides weight loss)
o Activates AMP-activated protein kinase
(AMPK), reducing glucogenesis • DPP4 Inhibitors
o Reduces plasma glucagon level o Dipeptidyl-peptidase 4 (DPP4) is an enzyme
o Slows GI absorption of glucose and stimulates that degrades incretin and GLP-1
glycolysis in tissues and blood glucose removal o Increases glucose-mediated insulin release and
o Facilitates lactate production, which can lead to decreases glucagon levels
lactic acidosis
• Islet Amyloid Polypeptide (IIAPP, amylin)
• Thiazolidinediones (Glitazones)- Euglycemics o Derived from islet amyloid deposits in pancreas
o Activates peroxisome proliferator-activated material from patients with longstanding type 2
receptor gamma (PPAR-y), a regulator the diabetes
transcription of genes encoding proteins o Modulate insulin release by acting as a negative
involved in carbohydrate and lipid metabolism, feedback on insulin secretion
thus resulting in glucose uptake, inhibited o Reduces glucagon secretion, slows gastric
gluconeogenesis, reduced lipid metabolism and emptying and decreases appetite
reduced hyperglycemia
• Bile acid sequestrants
o Inhibits farnesoid X receptor (FXR) activation, a
nuclear receptor with multiple effects on
cholesterol, glucose, and bile acid metabolism

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 DRUG DESCRIPTION/USE/EFFECT ADVERSE EFFECT
First-generation Tolbutamide Hypoglycemia
sulfonylureas • Safest sulfonylurea for elderly diabetics Glyburide and Glipizide
• Tolbutamide Chlorpropamide • Hypoglycemia is more common
• Chlorpropamide • Prolonged hypoglycemia more common in the elderly;
• Tolazamide tolazamide is similar, but with shorter duration and Tolbutamide and chlorpropamide
more slowly absorbed; it has active metabolites • Extensively bound to serum
proteins
• Drugs that compete for protein
Second-generation Used with caution in patients with CV disease or in elderly binding may enhance
sulfonylureas patients hypoglycemia
• Flushing (chlorpropamide,
Glyburide a.k.a. glibenclamide glyburide)
• Has (very slightly) active metabolites • Hematotoxicity
• Micronized form with questionable bioequivalence (chlorpropamide)
• CI in renal and hepatic disease
Glipizide (chlorpropamide, glyburide)
• Shortest half-life of 2nd gen sulfonylureas (2-4 h)
• Less likely to produce serious hypoglycemia than
Insulin
glyburide
Secretagogues
Glimepiride
• Single daily dose at a lowest of 1 mg is effective
in lowering bloodglucose, and has a long duration
of action

Meglitinides Repaglinide
• Repaglinide • Very fast onset of action, peak effect after 1 h, and is taken just before each meal for
• Nateglinide postprandial
• Caution in patients with hepatic or renal impairment
• Can be used for NIDDM patients with sulfur or sulfonylurea allergy

Nateglinide
• A phenylalanine deriva tive, and is the newest insulin secretagogue as of late
• Helps restore the immediate insulin release in response to a glucose load
• Has a special role in patients with isolated postprandial hyperglycemia
• Lowest incidence of hypoglycemia of all secretagogues, and is safe in reduced renal function
Metformin, FIRST-LINE drugs for type 2 DM • GI distress (nausea, diarrhea) is
phenformin • Used for new onset DM in middle-aged, obese most common
with impaired glucose tolerance and fasting • Impaired absorption of vitamin
Biguanides
hyperglycemia B12 after long-term therapy
• May impair hepatic metabolism of lactic acid
(dose related complication)
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 • Phenformin is the older biguanide associated with • CI: Renal or liver disease,
lactic acidosis alcoholism or conditions
predisposing to tissue anoxia
• Increased risk of lactic acidosis
Glitazones Used as monotherapy (70% efficacy) or in combination • Mild anemia and edema
with insulin or other oral antidiabetic drugs • Weight gain
• CHF
Pioglitazone • Increase bone fracture risk in
• With PPAR-alpha as well as PPAR-gamma women
Thiazolidine activity • Possible worsened cardio-
diones • Triglyceride effect is more significant than other vascular risk (rosiglitazone) and
thiazolidinediones hepatotoxicity (troglitazone)

Rosiglitazone
• Rapidly absorbed and highly protein bound, and is
metabolized to minimally active metabolites
Acarbose, • Reduced postprandial hyperglycemia, with lacks • Flatulence, diarrhea, and
voglibose, miglitol an effect on FBS abdominal pain
• Used as monotherapy or in combination with • CI in patients with inflammatory
Alpha- other antidiabetics disease conditions, renal
glucosidase • Both target the alpha -glucosidases impairment, and hepatic
inhibitors • Miglitol is six times more potent in inhibiting disease (acarbose)
sucrose, and patients with hypoglycemia taking
miglitol should be supplemented with glucose
(sucrose will not be useful in this case)
Exenatide, Exenatide • Nausea, vomiting and diarrhea
liraglutide • Synthetic analogue of glucagon-like-polypeptide 1 • Weight loss
(GLP-1), and is the first incretin therapy available • Necrotizing and hemorrhagic
GLP-1 pancreatitis
Liraglutide
agonists
• Long-acting synthetic GLP-1 analog
• Gained popularity because of improved glucose
control and associated anorexia and weight loss
in some users
Bile acid Colesevelam Used for DM 2 taking other medications or have not achieved adequate control with diet and exercise
sequestrant
Gliptins Adjunctive therapy to diet and exercise in the treatment of • Upper respiratory infections
DPP-4 individuals with type 2 diabetes who have failed to achieve • Headaches
Inhibitors glycemic • Allergic reactions
goals

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