Drugs to Treat Diabetes Flashcards
What is the standard treatment for type 1 diabetics?
insulin replacement therapy
What are the goals of therapy for treating type 1 diabetics?
maintain normal blood glucose levels (pre-meal: 90-130 mg/dL, post-meal: <180 mg/dL) and prevent tissue damage associated with hyperglycemia
What is the mechanism of action of insulin?
-activate insulin receptors
-regulate gene expression
-promote glucose transport
-promote synthesis of glycogen, lipid, and protein
Describe the structure of REGULAR insulin preparations
chain A & B linked with disulfide bonds, form hexamers conjugated with zinc
What is the onset of action of regular action insulin?
0.5-1h
When is the peak concentration after injection for regular injection?
2-3h
What is the duration of action of regular insulin?
3-8h
What preparations are fast-acting?
-aspart
-glulisine
-lispro
Describe the structure of FAST-ACTING insulin
chain A & B linked with disulfide bonds, forms monomers (makes it fast-acting)
What is the onset of action of fast-acting insulin?
less than 15 minutes
When is the peak concentration after injection for fast-acting insulin?
0.5-3h
What is the duration of action of fast-acting insulin?
2-4h
What preparations are intermediate acting?
NPH
Describe the preparation of NPH
NPH= neutral protamine Hagedorn, insulin complex with zinc and protamine intended to gradually release insulin
What is the dosing of intermediate insulin?
usually given 1-2 times a day in combination with short acting insulin
What is the onset of action of intermediate insulin?
2-5h
When is the peak concentration after injection of intermediate insulin?
4h
What is the duration of action of intermediate insulin?
4-12h
What preparations are long-acting?
-detemir
-glargine
-degludec
What is the duration of action of long-acting insulin?
20-25h
When is the peak concentration after injection for long-acting?
no peak
What insulin is used in insulin pumps?
short-acting
What are the adverse effects of insulin?
-hypoglycemia
-hypertrophy of subcutaneous fatty tissue if repeated injections at the same site
-insulin hypersensitivity (rare)
-hypokalemia (encourages K+ to go into the cell)
What are the drug interactions of insulin?
potassium-lowering medications due to the risk of hypokalemia, PPAR-gamma agonists (thiazolidinediones) may cause fluid retention and heart failure
What is the treatment for hypoglycemia?
-ingestion of sugary food or drinks
-glucagon for severe symptoms (SC, IM, IV injection)
Describe the indication and mechanism of action of dasiglucagon (Zegalogue)
treats severe hypoglycemia in patients >6 yo, glucagon receptor agonist- breaks down glycogen and releases glucose from the liver (hepatic stores of glycogen is necessary for desired effect)
What is the treatment of ketoacidosis?
aggressive IV hydration with electrolytes and insulin IV infusion
MOA: teplizumab-mzwv (Tzield)
delay the onset of stage 3 type 1 diabetes (disease onset, >80% pancreatic beta cells destroyed) in patients > 8 yo who are currently in stage 2 by binding to immune cells to deactivate them
MOA: sulfonylureas
bind to the sulfonylurea receptor (SUR) which forms a complex with Katp channel on the pancreatic beta cell membrane and blocks channel opening and depolarizes the cell- Ca2+ enters the cell and promotes the release of insulin
What drugs are sulfonylureas?
-glyburide
-glipizide
-glimepiride
note these are 2nd gen
What are the adverse effects of sulfonylureas?
hypoglycemia, weight gain, headache, dizziness
What are the precautions of sulfonylureas?
liver or kidney diseases because sulfonylureas are metabolized hepatically and excreted renally
What are the drug interactions of sulfonylureas?
sulfonylureas are extensively bound to plasma albumin so other drugs that are highly protein bound, such as: NSAIDs, salicylates, sulfonamides, probenecid, MAO inhibitors, and beta blocks would increase plasma concentration of sulfonylureas= increase side effects
MOA: meglitinides
bind to sulfonylurea receptor (SUR) in a distinct manner from sulfonylureas, but the also block Katp channel to promote depolarization of pancreatic beta cells and insulin secretion
faster acting so given before or within 30 minutes of meals to diminish postprandial hyperglycemia
What drugs are meglitinides?
-repaglinide
-nateglinide
MOA: GLP-1 agonists
incretin mimetics, regulate the pancreas to increase insulin release but decrease glucagon release, also increase glucose-mediated insulin release and slow gastric emptying time (increase satiety)
What drugs are GLP-1 agonists?
the -glutide’s
-exenatide
-albiglutide
-dulaglutide (Trulicity) +GIP agonist
-semaglutide (Ozempic- injection, Rybelsus- tablet)
-liraglutide (Victoza)
-tirzepatide (Mounjaro)
What are the adverse effects of GLP-1 agonists?
nausea/vomiting, increased risk of pancreatitis, hypoglycemia (risk is low, but may be increased if combined with sulfonylureas
What are the precautions with GLP-1 agonists?
renal disease
Which diabetes drugs are indicated for weight loss?
-semaglutide (Wegovy)
-tirzepatide (Zepbound)
What are the black box warnings for the diabetes drugs indicated for weight loss?
risk of thyroid C-cell tumors
What are the adverse effects of the diabetes drugs indicated for weight loss?
-acute pancreatitis
-acute gallbladder disease
-acute kidney injury
-hypoglycemia
-severe gastrointestinal disease (tirzepatide only)
MOA: DPP-4 inhibitors
blocks DDP-4 (serine protease) that inactivates GLP-1, so increases GLP-1 and GIP activity, and increases glucose-mediated insulin release, decrease glucagon, decreased gastric emptying
typically combined with other agents
What drugs are DPP-4 inhibitors?
the -gliptin’s
-alogliptin
-sitagliptin (Januvia)
-saxagliptin
-linagliptin
What are the adverse effects of DPP-4 inhibitors?
nausea, running nose, upper respiratory infection
What is the first line therapy for type 2 diabetes?
metformin
MOA: metformin
biguanides, not fully understood, but stimulate AMP-activated protein kinase (AMPK) and reduce hepatic glucose production
What is the dosing of metformin?
500mg with meals, commonly adjusted to 1000mg daily with meals
What are the contraindications for metformin?
severe renal impairment
What are the adverse effects of metformin?
hypoglycemia (if used with insulin), GI related symptoms (anorexia, nausea, vomiting, abdominal discomfort, diarrhea)
What are the precautions of metformin?
risk of lactic acidosis (especially with alcohol intake) and vitamin B12 deficiency
MOA: thiazolidinediones
agonists for peroxisome proliferator-activated receptor gamma (PPARgamma) which is predominantly expressed on adipose tissue that regulates glucose and lipid metabolism- INCREASES tissue sensitivity to insulin (“insulin sensitizers”, requires insulin so not used to treat type 1 diabetics)
also decrease lipolysis
What is the onset of action of thiazoldinediones?
slow, effects not seen for 1-3 months
What drugs are thiazolidinediones?
the -glitazone’s
-pioglitazone
-rosiglitazone
What are the adverse effects of thiazolidinediones?
fluid retention, edema, weight gain
What are the drug interactions of thiazolidinediones?
insulin= may cause hypoglycemia, fluid retention and heart failure
MOA: SGLT2 inhibitors
blocks glucose reabsorption through the proximal tubules by sodium-glucose transporters (SGLTs), SGLT2 is responsible for 90% of this action so blood glucose is decreased through excretion of glucose in the urine
What drugs are SGLT2 inhibitors?
-canagliflozin
-dapagliflozin (Farxiga)
-empagliflozin (Jardiance)
-ertugliflozin (Steglatro)
-bexagliflozin
What are the adverse effects of SGLT2 inhibitors?
ketoacidosis
What are alpha-glucosidase inhibitors?
starch blockers, delay digestion of starches (carbohydrates) to reduce post-meal glucose increase (drugs= acarbose and miglitol)
What are the side effects of alpha-glucosidase inhibitors?
flatulence, diarrhea, and abdominal pain
What are amylin analogs- pramlintide (Symlin)?
amylin analogs decreases glucagon secretion and slows GI emptying, approved for type 1 and type 2 diabetes to take adjunct with insulin at mealtime
What is bile acid sequestrant, colesevelam (Welchol)?
used for type 2 diabetes in adjunct with other diabetes medication and hypercholesterolemia
What is bromocriptine?
dopamine agonist that has modest lowering effects on blood glucose, mechanism unknown
