Diabetes Drugs

Drug Name Class Clinical Uses Onset Action Peak Action Effective Duration
• Diabetic ketoacidosis
Regular Short-Acting Insulin, synthetic • Perioperative management of insulin-
requiring diabetics • 30-60 min • 2 hr • 6-8 hr
Insulin (IV) analog
• Used to treat hyperkalemia, given w/ glucose to
prevent hypoglycemia
Lipsro, Aspart, Rapidly-Acting Insulin, reduced
• Pre-prandial (meal) use • 5-15 min • 1-1.5 hr • 3-4 hr
Glulisine hexamer/polymer formation
NPH (neutral Intermediate-Acting Insulin • Basal use
protamine - Delayed absorption due to • Usually mixed w/ regular or rapid and given • 2-4 hr • 6-7 hr • 10-20 hr
hagedorn) combining w/ protamine 2-4x/day
• Acidic formulation, precipitates in body
Glargine Long-Acting Insulins (Peak- pH. Allows insulin molecules to slowly • 0.5-1 hr • Flat • ~24 hr
less) dissolve from crystals.
- Basal use
• Reversible albumin binding. Less weight
Detemir - Used w/ bolus of • 0.5-1 hr • Flat • 17 hr
gain than glargine.
Rapid-Acting at meals
Degludec • Self-associates into multihexameric chains • 0.5-1.5 hr • Flat • > 42 hr
• Preprandial insulin
Inhaled Insulin
Technosphere • CONTRA: pts w/ asthma and COPD. May • 5-15 min • 1 hr • 3 hr
Rapid onset, shorter duration
reduce lung function (decreased FEV)
Side Eff.: Hypoglycemia - blood glucose < 60 mg/dl. Due
to: Too much insulin and/or not enough food (glucose)
• Sweating, anxiety, increased irritability Agents which (­) blood glucose (esp. in Agents which may (­) the risk of insulin
• Tachycardia, palpitations, tremor diabetics) hypoglycemia
• Weakness, Hunger, Blurred vision • Catecholamines Thyroid hormone • Ethanol
• Severe: Seizures, Coma • Isoniazid Glucocorticoids • ACE inhibitors Somatostatin
• Increased sympathetic output • Fluoxetine
• Calcitonin Phenothiazines MAO inhibitors
Weight Gain:
• Insulin promotes fatty acid & protein synthesis
• Oral contraceptives Somatropin • Anabolic steroids b adrenergic blockers
Other adverse: • Morphine • vigorous, unaccustomed exercise
• Hypertrophy of subcutaneous fatty tissue if inject repeatedly
at same site – prevent by avoiding specific injection site
£ blood glucose levels through • Emergency treatment of severe hypoglycemic Side Effects
activation of glucagon receptor: reactions in pts w/ T1DM when unconsciousness • Transient nausea and occasional vomiting can
Gs coupled receptor: • Reversing the cardiac effects of an overdose of β- result from glucagon administration.
Glucagon • £ cAMP leading to blocking agents because of its ability to increase • These are generally mild, and glucagon is
catabolism of stored glycogen cAMP production in the heart independent of β- relatively free of severe adverse reactions.
• £ gluconeogenesis, and receptor function (due to independent activation of Contraindicated in patient with
ketogenesis cAMP). pheochromocytoma
- Weight loss, exercise: improve glycose levels
- First-line treatment usually lifestyle modification for 3-6 months, if initial A1c is not markedly £
Drug Name MOA Clinical Uses Side Effects Contraindications Other
Insulin Secretagogues
Sulfonylureas
• Act. of sulfonylurea • Hypoglycemia • Caution in patients with
Glipizide • Orally administered
• Weight gain cardiovascular disease or in elderly
Glyburide receptor on ATP- • Inexpensive!!
sensitive K channels Type 2 diabetes • Disulfiram-like patients
Glimepiride +

(close) in pancreatic w/ changes to diet & rxns Certain drugs may potentiate action by
b-cells resulting in £ exercise (sulfonylureas) displacing it from plasma protein-binding • Orally administered
Meglitinides more depolarization, HbA1c ¤: 1-2% • GI disturbances sites (β blockers, chloramphenicol, coumarin, • Rapid onset (1 hr post
increased insulin (N/V/D, anorexia, MAOIs, NSAIDs, probenicid, salicylates, and ingestion), useful in
Repaglinide sulfonamide) or altering its metabolism controlling
secretion hunger) (gemfibrozil, itraconazole, trimethoprim,
cyclosporin, simvastatin, clarithromycin). postprandial glucose
Sulfonylureas Interactions
• Drugs that compete for protein binding (NSAIDS, probenecid, sulfonamides, warfarin)
Enhanced • Antacids might increase the absorption of the sulfonylureas and produce a higher peak concentration of the drug
hypoglycemia • Allopurinol, chloramphenicol, cimetidine, and erythromycin inhibit the metabolism of the drugs→higher [drug]
• Ethanol may enhance action of sulfonylureas
• Corticosteroids, diuretics (thiazide) & lithium have intrinsic hyperglycemic activity; dosage of sulfonylurea may need to be modified.
Decreased
• β-adrenergic blocking agents can ¤ hypoglycemic effects of sulfonylureas by inhibiting insulin secretion, £peripheral insulin resistance.
effect of
• Endotehlin receptor antagonist bosentan (only with glyburide)
sulfonylureas
• Phenytoin, phenobarbitone, rifabutin and rifampicin induce the hepatic enzymes which metabolize the drugs→lower [drug]
Biguanides (Insulin Sensitizer) à Action on Liver, Muscle, Adipose to Lower Glucose
Act. of AMP-activated
kinase (AMPK): • GI disturbances
• First-line • NO weight gain
• ¯ hepatic glucose (N/V/D, cramping) • Patients susceptible to lactic
therapy! (maybe weight loss??)
production (inhibits • Lactic acidosis acidosis such as those with renal
Type 2 diabetes or hypoglycemia
Metformin gluconeogenesis) (rare, life- insufficiency & renal failure, liver
w/ changes to diet & • Held when pt acutely
• ­ muscle and fat threatening) disease or alcohol abuse, acute heart
£ exercise ill & for IV contrast
glycolysis & glucose • ¤ vitamin B12 failure, hypoxia…
• HbA1c ¤: 1-2% tests
uptake absorption
• £ insulin sensitivity
Thiazolidinediones (TZDs) (Insulin Sensitizer) à PPAR-g Activators
• Activation of peroxisome • Orally administered
proliferator activated • Type 2 diabetes • Metabolized by CYP2C8 and
receptor-g, a nuclear w/ changes to diet • Weight gain Contraindicated: CYP3A4 to active metabolites à can
hormone receptor for glucose and increased • Edema, heart • Patients with affect bioavailability of many drugs
Pioglitazone and lipid metabolism including estrogen-containing oral
exercise failure moderate-severe
• ¤ insulin resistance HbA1c ¤: 0.5- • Bone fracture heart failure contraceptives
• £ insulin sensitivity/ 1.4% • NO hypoglycemia
glucose utilization • ¤ triglycerides & £ HDL
a-Glucosidase Inhibitors à Decreased/Slows Glucose Absorption
• ¯ GI (small intestine) • Type 2 diabetes
• Orally administered
glucose absorption via w/ changes to diet and • GI disturbances (diarrhea,
Acarbose • Decreases postprandial glycemia
inhibition of a- £ exercise flatulence, nausea/vomiting)
• NO weight gain or hypoglycemia
glucosidase • HbA1c ¤: 0.5-0.8%
Glucagon-Like Peptide 1 (GLP-1) Agonist à Incretin Mimic & Inhibitor
• Glucagon-like peptide 1 • GI disturbances
(GLP-1) receptor • Type 2 diabetes, w/ (nausea/vomiting)
• SQ injection, ¤ some CV risk factors
agonists à potentiate changes to diet & £ • Possible pancreatitis
Exenatide • Weight LOSS (2-3 kg)
glucose-mediated insulin exercise • Possible thyroid tumor
• No hypoglycemia
secretion and suppress • HbA1c ¤: 0.5-1.5% Contraindicated in those ­ risk
glucagon release for thyroid cancer, renal impair
DPP-4 Inhibitors à Incretin Mimic & Inhibitor
• Well tolerated although
• Inhibit DDP-4 resulting • Type 2 diabetes, w/
potential for hypersensitivity
in prolonged action of changes to diet & £ • Orally administered
Sitagliptin reactions (anaphylaxis,
endogenous GLP-1 and exercise • N) weight gain or hypoglycemia
angioedema, exfoliative skin
GIP • HbA1c ¤: 0.5-0.8%
reactions)
Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitor
• ­ incidence of genital infections Contraindicated
• Decrease glucose and UTIs • Pts w/ renal • Orally administered
• Type 2 diabetes, w/
reabsorption from • Osmotic diuresis resulting in disease • Efficacy reduced in
changes to diet & £
Canagliflozin proximal tubule resulting intravascular volume • Pts w/ T1DM chronic kidney disease
exercise
in increased renal contraction and hypotension (due to DKA) • Weight LOSS (2-3 kg)
• HbA1c ¤: 0.9-1.2%
glucose excretion • Potential £ in bone fractures • T2DM prone to • No hypoglycemia
• Modest increase in LDL ketosis
Amylin Mimetic; Amylin is normally released from b-cells with insulin but is absent in T1 and diminished in T2 DM
• SQ Injection w/ insulin
• Amylin polypeptide analog that • Type 1 and 2 diabetes, • Hypoglycemia
• Should not be mixed with insulins in the
Pramlintide suppresses glucagon release. postprandial • GI (nausea/vomiting,
syringe, increases satiety
• Slow gastric emptying • HbA1c ¤: 0.25-0.5% anorexia)
• Weight LOSS
Bile Acid-Binding Resins
• Bile acid sequestrants, unclear • T2DM w/ changes to • GI (constipation, nausea) • Orally administered
Colesevelam how lowers glucose may reduce diet & £ exercise • May decrease absorption of • Can £ triglycerides, ¤LDL
glucose absorption • HbA1c ¤: 0.25-0.5% other drugs • No weight gain or hypoglycemia