Cecil Diabetes Medications Flashcards
What does metformin do?
biguanide drug
most widely used anti diabetic!
inhibits mitochondrial complex I which effects oxidative phosphorylation and cellular energy charge
regulates activity of 5’-adenosine monophosphate- activated protein kinase
Lowers glucose levels through suppression of hepatic glucose production
Can also enhance insulin sensitively (improved insulin-mediated glucose uptake) and limit intestinal glucose absorption
How often do people take metformin?
2x a day
What’s the most common side effect of metformin?
Hypoglycemia rarely occurs
Most common side effect is gastrointestinal intolerance like dyspepsia or diarrhea - this can be minimized by slow upward dose titration
B12 malabsorption leading to B12 deficiency has also been reported
Lactic acidosis is the most serious but rare and happens almost exclusively in patients with renal insufficiency
What is an extra benefit side effect of metformin?
Reduction of cardiovascular and all-cause mortality in the UK
What has metformin also been used for?
Diabetes prevention
Treatment of polycystic ovary syndrome
Which people shouldn’t you use metformin for?
If someone has an estimated glomerular filtration rate (GFR) of 45 mL/minute or lower you need to be cautious
If they have a GFR of 30 mL/minute they should be discontinued
Related to renal function - metformin can be bad for renal insufficiency
What do thiazolidinediones do?
Improve insulin-mediated glucose uptake and reduce hepatic glucose production
They bind to a nuclear receptor, peroxisome proliferator-activated receptor γ, and regulate the transcription of a bunch of genes involved in carbohydrate and lipid metabolism
Reduces lipolysis, increases fat mass, and causes redistribution of fat away from visceral to subcutaneous depots
Increases circulating adiponectin, an adipokine with insulin-sensitizing and anti-inflammatory properties = this plays a role in the glucose-lowering effect of these drugs
which medications are thiazolidinediones?
Rosiglitazone
Pioglitazone
How often are thiazolidinediones taken?
Orally once a day
What are the side effects of thiazolidinediones?
- weight gain
- fluid retention
- precipitation or worsening of congestive heart failure
- increase in fractures in postmenopausal women
- increased risk of bladder cancer
What are the issues with rosiglitazone?
It’s a thiazolidinediones
Has potential cardiovascular toxicity - this is controversial though
These effects haven’t been observed in pioglitazone (the other thiazolidinedione)
What types of diabetes medications are insulin sensitizers?
- Metformin
2. Thiazolidinediones
What types of diabetes medications are insulin secretagogues?
- Sulfonylureas
- Glinides
- Incretin-based therapies/GLP-1 agonists
- Incretin-based therapies/DPP-4 inhibitors
What are other pharmacological agents for diabetes?
- SGLT2 inhibitors
2. α-glucosidase inhibitors
What are sulfonylureas?
Insulin secretagogues
They bind to ATP-sensitive K+ channel in the B-cell membrane which leads to membrane depolarization and the release of insulin from preformed secretory granules
You need a sufficient number of intact B cells then in order for this drug to be efficient!
Can be used as mono therapy or in combination with other drugs
What is the oldest available oral anti diabetes drug?
Sulfonylurea
What are common sulfonylureas?
- Glipizide
- Glyburide
- Glimepiride
What are the side effects of sulfonylureas?
Potential to cause hypoglycemia because insulin se creation occurs regardless of if there’s ambient plasma glucose
Modest weight gain
May increase the risk of cardiovascular events and mortality - controversial though
Still the most widely used anti diabetic medications
What are glinides?
Non-sulfonylurea insulin secretagogues
Bind to ATP-sensitive K+ channel in the B-cell membrane
Their onset and duration of action are much shorter than sulfonylureas and the frequency of fasting hypoglycemia may be less
Which medications are glinides?
Repaglinide
Nateglinide
How often do you take glinides?
Orally before each meal
Good for patients with inconsistent meal timing or content
what are incretin-based therapies/GLP1 agonists?
they stimulate insulin secretion by binding to GLP1 receptors on B cells
have less potential to cause hypoglycemia than sulfonylureas and glinides because they increase glucose-stimulated insulin secretion
they also suppress hepatic glucose production by reducing glucagon secretion
they also delay gastric emptying, suppress appetite, result in modest weight loss
which medication are incretin-based therapies/GLP1 agonists?
exenatide and liraglutide
how are GLP1 agonists given?
injection once or twice a day
weekly long-acting formula is also available
what are the side effects of GLP1 agonists?
gastrointestinal intolerance = nausea and vomiting (can be minimized with an initial small dose and titration upwards)
increased risk of acute pancreatitis (still not proven)
increase in C-cell hyperplasia and medullary thyroid cancer in mice, not sure about humans
what are incretin-based therapies/DPP-4 inhibitors?
DPP4 is a serine protease
DPP4 inhibitors prevent the breakdown of GLP1 which prolongs its effects
rarely cause hypoglycemia, less GI side effects, weight neutral
which medications are DPP4 inhibitors?
- sitagliptin
- saxaglipitin
- linagliptin
how often are DPP4 inhibitors taken?
orally once a day
what are the side effects of DPP4 inhibitors?
potential risk of pancreatitis and medullary thyroid cancer has been raised but not confirmed
what are the other types of pharmacological agents used for diabetics?
- SGLT2 inhibitors
2. α-glucosidase inhibitors
what are SGLT2 inhibitors?
they inhibit the sodium glucose cotransporter 2 in the proximal renal ruble
this inhibition prevents the reabsorption of filtered glucose and results in glycosuria (glucose in urine)
which medications of SGLT2 inhibitors?
canagliflozin and dapagliflozin
what are side effects of SGLT2 inhibitors?
increase in mycotic genital infections (fungal)
hyperkalemia, UTIs and decreased BP have also been reported
what are α-glucosidase inhibitors?
inhibit α-glucosidase enzymes in the intestinal lumen that are required for the breakdown and absorption of complex carbs
α-glucosidase inhibitors slow carb absorption in the small intestine which delays the delivery of glucose and allows for better coordination with sluggish insulin secretion
don’t cause weight change or hypoglycemia
which medications are α-glucosidase inhibitors?
acarbose and miglitol
how often do you take α-glucosidase inhibitors?
with every meal
what are the side effects of α-glucosidase inhibitors?
flatulence and bloating due to colonic bacteria action on intestinal contents
