Cecil Diabetes Medications

Question 1

What does metformin do?

Answer 1

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

Question 2

How often do people take metformin?

Answer 2

2x a day

Question 3

What’s the most common side effect of metformin?

Answer 3

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

Question 4

What is an extra benefit side effect of metformin?

Answer 4

Reduction of cardiovascular and all-cause mortality in the UK

Question 5

What has metformin also been used for?

Answer 5

Diabetes prevention

Treatment of polycystic ovary syndrome

Question 6

Which people shouldn’t you use metformin for?

Answer 6

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

Question 7

What do thiazolidinediones do?

Answer 7

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

Question 8

which medications are thiazolidinediones?

Answer 8

Rosiglitazone

Pioglitazone

Question 9

How often are thiazolidinediones taken?

Answer 9

Orally once a day

Question 10

What are the side effects of thiazolidinediones?

Answer 10

• weight gain
• fluid retention
• precipitation or worsening of congestive heart failure
• increase in fractures in postmenopausal women
• increased risk of bladder cancer

Question 11

What are the issues with rosiglitazone?

Answer 11

It’s a thiazolidinediones

Has potential cardiovascular toxicity - this is controversial though

These effects haven’t been observed in pioglitazone (the other thiazolidinedione)

Question 12

What types of diabetes medications are insulin sensitizers?

Answer 12

1. Metformin

2. Thiazolidinediones

Question 13

What types of diabetes medications are insulin secretagogues?

Answer 13

1. Sulfonylureas
2. Glinides
3. Incretin-based therapies/GLP-1 agonists
4. Incretin-based therapies/DPP-4 inhibitors

Question 14

What are other pharmacological agents for diabetes?

Answer 14

1. SGLT2 inhibitors

2. α-glucosidase inhibitors

Question 15

What are sulfonylureas?

Answer 15

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

Question 16

What is the oldest available oral anti diabetes drug?

Answer 16

Sulfonylurea

Question 17

What are common sulfonylureas?

Answer 17

1. Glipizide
2. Glyburide
3. Glimepiride

Question 18

What are the side effects of sulfonylureas?

Answer 18

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

Question 19

What are glinides?

Answer 19

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

Question 20

Which medications are glinides?

Answer 20

Repaglinide

Nateglinide

Question 21

How often do you take glinides?

Answer 21

Orally before each meal

Good for patients with inconsistent meal timing or content

Question 22

what are incretin-based therapies/GLP1 agonists?

Answer 22

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

Question 23

which medication are incretin-based therapies/GLP1 agonists?

Answer 23

exenatide and liraglutide

Question 24

how are GLP1 agonists given?

Answer 24

injection once or twice a day

weekly long-acting formula is also available

Question 25

what are the side effects of GLP1 agonists?

Answer 25

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

Question 26

what are incretin-based therapies/DPP-4 inhibitors?

Answer 26

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

Question 27

which medications are DPP4 inhibitors?

Answer 27

• sitagliptin
• saxaglipitin
• linagliptin

Question 28

how often are DPP4 inhibitors taken?

Answer 28

orally once a day

Question 29

what are the side effects of DPP4 inhibitors?

Answer 29

potential risk of pancreatitis and medullary thyroid cancer has been raised but not confirmed

Question 30

what are the other types of pharmacological agents used for diabetics?

Answer 30

1. SGLT2 inhibitors

2. α-glucosidase inhibitors

Question 31

what are SGLT2 inhibitors?

Answer 31

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)

Question 32

which medications of SGLT2 inhibitors?

Answer 32

canagliflozin and dapagliflozin

Question 33

what are side effects of SGLT2 inhibitors?

Answer 33

increase in mycotic genital infections (fungal)

hyperkalemia, UTIs and decreased BP have also been reported

Question 34

what are α-glucosidase inhibitors?

Answer 34

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

Question 35

which medications are α-glucosidase inhibitors?

Answer 35

acarbose and miglitol

Question 36

how often do you take α-glucosidase inhibitors?

Answer 36

with every meal

Question 37

what are the side effects of α-glucosidase inhibitors?

Answer 37

flatulence and bloating due to colonic bacteria action on intestinal contents