Oral Antidiabetic Agents

Question 1

Metformin

Answer 1

Oral Antidiabetic agents
Advantages
-weight neutral
-does not cause hypoglycemia
-reduces hg A1C by 1.5-2%
-indirectly reduces insulin levels
-reduces fasting plasma glucose
-biguanides
MOA (works on liver and muscle)
-reduces hepatic glucose production (DEC gluconeogenesis)
-DEC intestinal absorption of glucose
-INC peripheral glucose uptake by helping to improve insulin sensitivity
ADE
-lactic acidosis (due to anaerobic metabolism)
-GI issues most common (N, abdominal pain, bloating)
-DEC Vitamin B12
-start w/ low does and increase slowly to avoid side effects
Contraindications
-Serum creatinine
-alcohol abuse
-liver/kidney failure
-hold prior to administration of IV radiocontrast dye
-not for Type I DM
Drug interactions
-alcohol
-cationic meds (cimetidine, furosemide, nifedipine)
-

Question 2

(Glyburide, glipizide, glimepiride)

Answer 2

Oral antidiabetic agents = Sulfonylureas
Advantages
-*contributes to reduction in post-prandial glucose=like rapid acting insulin
-reduces hg A1C by 1-2%
-reduces fasting plasma glucose
Therapeutic considerations
-*use w/ caution in elderly and in pts w/ renal impairment
-*secondary failure
MOA
-stimulates insulin release from pancreatic B-cells
-reduces glucose output from liver
-INC insulin sensitivity of peripheral target sites
ADE
-*hypoglycemia
-*weight gain
-heart burn
-nausea
-Disulfuram-like rx
-abnormal liver fx tests
Contraindications
-hypersensitivity to sulfonamides
-pregnancy
-type I DM
Drug interactions
-INC effects of CYP inhibitors (azole antifungals, gemfibrozil, MAOIs, H2RAs)
-DEC effects of CYP inducers (hydantoins, rifampin, diuretics)

Question 3

(Repaglinide, nateglinide)

Answer 3

Oral antidiabetic agents = Meglitinide Derivatives
Advantages
-*reduces post prandial blood glucose
-*may be useful in pats who skip meals
-reduces HG A1C by 0.5-1.5%
-short duration of action
MOA
-stimulates insulin release from pancreatic B-cells
ADE
-hypoglycemia
-weight gain
-HA
-diarrhea
Contraindications
-*use caution in pts w/ reduced hepatic function or renal impairment
-Type I DM
Drug interactions
-INC effects of CYP inhibitors (NSAIDs, B-blockers, MAOIs, statins, azole antifungals)

Question 4

(Pioglitazone, rosiglatazone)

Answer 4

Oral antidiabetic agents = Thiazolindinediones (TZDs)
Advantages
-*does not cause hypoglycemia
-*reduces fasting plasma glucose
-reduces HG A1C 0.5-1.4%
-favorable effects on lipids
MOA
-agonist for peroxisome proliferator-activated receptor-gamma (PPARgamma)
-improves target cell responses to insulin (INC sensitivity)
ADE
-CHF
-hepatic dysfx
-*weight gain
-edema
Contraindications
-*Class III or IV heart failure
-elevated transaminases (ALT, AST)
-use caution in *premenopausal women
-*bladder cancer
Drug interactions
-INC effects (atazanavir, ritonavir, gemifibrozil)
-DEC effects (rifampin, carbamazepine, phenytoin)

Question 5

(Acarbose)

Answer 5

Oral antidiabetic agent = a-glucosidase inhibitor
Advantages
-reduces post prandial glucose
-acts locally in the gut
-*weight neutral
-reduces HG A1C 0.5-0.8%
MOA
-competitive inhibitor of pancreatic a-amylase and intestinal brush border a-glucosidases
-reduces absorption of glucose from the gut
-delays hydrolysis of ingested complex carbohydrates
-inhibits the metabolism of sucrose to glucose and fructose
ADE
-GI issues (farts, abdominal pain, diarrhea)
-elevated serum transaminases (severe adverse events)
Contraindications
-partial or potential for small bowel obstruction
-inflammatory bowel disease chronic ulceration

Question 6

(Sitagliptin, Linagliptin)

Answer 6

Oral antidiabetic agents = Dipeptidyl Peptidase IV Inhibitors (DPP-IV)
-unclear effect regarding specificity and long term side effects
-limited data regarding efficacy, safety
MOA
-inhibits enzyme resulting in prolonged active incretin levels
ADE
-*pancreatitis
-HA
-diarrhea
Contraindications
-Type I DM
-DKA

Question 7

(Canagliflozin, dapagliflozin)

Answer 7

Oral antidiabetic agent = SGLT2 Inhibitors
-novel class of agent
-safety and efficacy data lacking
-may be useful when metformin or other orals contraindicated or not tolerated
Advantages
-reduces fasting plasma glucose
-weight neutral or weight loss
-unique MOA
-reduces HG A1C by 0.5-1%
-does not cause hypoglycemia
MOA
-inhibition of sodium-glucose co-transporter
-enhancement of urinary glucose excretion
ADE
-GU (balanitis, vulvovaginitis, genital mycotic infx)
-CV (hypotension, intravascular volume depletion)
-electrolyte abnormalities
Contraindications
-*renal dysfx