Diabetes medications

Background

• Hypoglycemics
  • Sulfonylureas
  • Benzoic acid derivatives
• Antihyperglycemics
  • Biguanides
  • Alpha glucosidase inhibitors
  • Thiazolidinediones

Common Anti-hyperglycemic Drugs and Pharmacology

Drug	Pharmacology
	Onset	Peak	Duration
Rapid-acting insulin Aspart (Novolog) Lispro (Humalog)	15-30min	1-2h	3-5h
Short-acting insulin Regular	30-60min	2-4h	6-10h
Intermediate-acting insulin NPH (Humulin, Novolin)	1-3h	4-12h	18-24h
Long-acting insulin Glargine (Lantus)	2-4h	None	24h
Sulfonylurea Glimepiride Glipizide (Glucotrol) Glyburide (Glycron, Micronase)	–	2-6h	12-24h

See also GLP-1 agonists

Biguanides (Metformin)

Suppresses liver glucose production

Dose

Metformin 500mg PO BID is first-line agent for type II diabetics

• Do not prescribe if creatinine > 1.4 (GFR <40), CHF, hepatic insufficiency, ETOH abuse
• Should be withheld for 48hr after IV contrast

Side Effects

• Lactic acidosis (due to increased lactate production)
  • Seen almost exclusively in patients with renal failure
• Nausea, diarrhea, crampy abdominal pain

Toxicity

• Almost never causes hypoglycemia when taken alone, but can exacerbate hypoglycemia when taken in combination with hypoglycemic agents
• Toxic dose unknown
• Management: Supportive care

Sulfonylureas

• Glipizide, glyburide
• Increase insulin secretion
• Hypoglycemia is the major adverse effect (especially with glyburide)

Alpha Glucosidase Inhibitors

• Acarbose, miglitol, voglibose
• Competitively and reversibly inhibit alpha glucosidase brush border hydrolase enzyme- makes postprandial decrease in carbohydrate absorption since complex polysaccharides not broken down into absorbable monosaccharides. Does not affect lactose absorption
• Taken with first bite of each meal
• Since limited absorption, stays in gut and side effects mostly GI- bloating, gas, diarrhea
  • acarbose- can cause transaminitis/ liver inj
• Contraindications- cirrhosis, IBD, malabsorption syndrome
• Do not cause hypoglycemia when used as monotherapy
  • If hypoglycemic- sucrose/ table sugar will not work- use glucose- PO or IV
• Since minimal absorption- systemic toxicity from OD unlikely

Thiazolidinediones

• Rosiglitazone and poiglitazone
• Enhance insulin effect on muscle, fat, liver without increasing pancreatic insulin secretion
• Protein bound and hepatic metabolism - avoid in patients with liver disease
• Side effects- induces ovulation, decreases effectiveness of OCP's, increases plasma volume (bad if CHF)

Benzoic Acid Derivatives

• Repaglinide- monotherapy or combined with metformin
• binds to ATP dependent potassium channel like sulfonyls but at different site.
• Unlike sulfonyls, it decreases insulin levels
• Dose 30 min before meal to decrease postprandial hyperglycemia

GLP-1 agonists

• Exanatide (Byetta and Bydureon), Liraglutide (Victoza)
• Synthetic glucagon-like peptide-1 (GLP-1) receptor agonists
• Stimulates insulin release from pancreatic islet cells
• May promote weight loss by slowing gastric emptying and increasing satiety

DPP-4 inhibitors

• Sitagliptin, saxagliptin, linagliptin, alogliptin
• Block DPP-4, which leads to increased activity of incretins, which inhibit glucagon release, which in turn increase insulin secretion and slow gastric emptying, ultimately decreasing blood glucose levels
• Potential serious adverse events include acute pancreatitis, anaphylaxis/angioedema, SJS

SGLT-2 inhibitors

• Canagliflozin (Invokana), Dapagliflozin (Farxiga), Empagliflozin (Jardiance)
• Inhibit sodium-glucose cotransporter 2, decreasing glucose reabsorption in the proximal tubule
• Potential serious adverse event: euglycemic DKA

See Also

• Diabetes Mellitus (Main)