Diabetes Medications
- Biguanides
- Sulfonylureas
- Meglitinide derivatives
- Alpha-glucosidase inhibitors
- thiazolidinediones (TZDs)
- Glucagonlike peptide-1 (GLP-1) agonists
- dipeptidyl peptidase IV (DPP-4) inhibitors
- Selective sodium-glucose transporter-2 (SGLT-2)
- insulins
example of biguanides
metformin (glucophage)
metformin indication
type 2 DM
PCOS
pre-diabetes
metformin CI
- metabolic acidosis
2. moderate to severe CKD
metformin MOA
- decrease hepatic glucose production
- decreases intestinal absorption of glucose
- improves insulin sensitivity by increases peripheral glucose uptake
metformin monotherapy or combo?
both
how much does metformin lower HbA1c
1-2%
metformin SE
- GI - abdominal pain, nausea, diarrhea
- reduced absorption of Vit B12 and folate
- mild weight loss
- hypoglycemia (but not really)
- lactic acidosis
Sulfonylurea examples
- glyburide / glynase
- glipizide / glucotrol
- glimerpiride / amaryl
Sulfonylurea MOA
- stimulate insulin secretion from beta cells of pancreas
2. reduce serum glucagon levels
how much do sulfonylureas lower HbA1c
1-2%
Sulfonylurea indications
- DM type 2
Sulfonylurea CI
- Type I DM
2. pregnancy
monotherapy or combo?
both
Sulfonylurea SE
- hypoglycemia
- flushing (w/ alcohol)
- weight gain
- tolerance - less effective over time
- anemia/thrombocytopenia
who are Sulfonylureas not the best for
diabetic who is not good at scheduling meals or who like to drink alcohol
Meglitinides examples
- Repaglinide / Prandin
Meglitinides indications
- DM type 2
2. postprandial hyperglycemia
Meglitinides CI
concomitant gemfibrozil (cholesterol med) and repaglinide/Prandin sulfonylureas
Meglitinides MOA
short acting, stimulate release of insulin from beta cells
who are Meglitinides good for
significantly elevated blood sugar post meals
irregular meals!
Meglitinides SE
- hypoglycemia
2. weight gain
special consideration for Meglitinides
dose adjust if liver impairment
check LFTs, urine microalbumin at lease once a year
alpha glucosidase inhibitors (AGIs) example
- acarbose / precose
not really seen
alpha glucosidase inhibitors (AGIs) indications
- DM type 2
- predominantly postprandial hyperglycemia
- new onset diabetes w/ mild HTN
alpha glucosidase inhibitors (AGIs) CI
- IBS
2. IBD
alpha glucosidase inhibitors (AGIs) monotherapy or combo?
both - combo w/ sulfonylureas
alpha glucosidase inhibitors (AGIs) MOA
inhibit breakdown of carbohydrates to glucose n the gut - act locally in the gut
alpha glucosidase inhibitors (AGIs) SE
- flatulence
- bloating
- abdominal discomfort
- diarrhea
- increased liver enzymes
Thiazolidinedoiones examples
- rosiglitazone / Avandia
2. Pioglitazone / Actos
TZD Indications
DM type 2
TZD CIs
- heat failure
- pregnancy
- breastfeeding/lactation
how much do TZDs lower HbA1c
1-2%
when to use TZDs
- if someone doesn’t tolerate metformin
2. use w/ metformin if unable to tolerate high levels of meformin
TZDs SE
- weight gain
- edema
- cardiovascular
- fractures
- raise HDL
if you have a diabetic patient who also tends to be a fluid retaining hypertensive, what medication class should you avoid
TZDs b/c can cause edema
What does GLP-1 agonists stand for?
glucagonlike peptide-1 agonist
examples of long-acting GLP-1 analogs
Liraglutide (Victoza)
examples of prolonged-acting GLP-1 analogs
- dulaglutide (Trulicity)
2. semglutide (Ozempic)
difference between long-acting and prolonged acting GLP-1 agonists
long-acting taken daily vs. prolonged-acting taken weekly
GLP-1 agonists monotherapy or combo?
only add-in therapy (combo) - patients who have not achieved glycemic goals using metformin, a sulfonylurea or both, in combo with TZD +/- metformin
GLP-1 agonist MOA
- mimic endogenous incretin GLP-1
- stimulate glucose-dependent insulin release
- reduce glucagon
- slow gastric emptying
- may prevent beta-cell apoptosis
GLP-1 agonist SE
- weight loss
- thyroid c-cell tumors / medullary thyroid cancer
- Steven-Johnson syndrome
- angioedema
- upset stomach
- pancreatitis
- cholelithiasis
- change in vision (semiglutide/ozempic)
GLP-1 agonist CI
- personal or family history of medullary thyroid cancer
2. exenatide in end stage renal disease
what does DPP-IV inhibitor stand for?
Dipeptidyl-peptidase IV inhibitors
DPP-IV inhibitor examples
- Linagliptin (Tradjenta)
2. Sitagliptin (Januvia)
DPP-IV inhibitor monotherapy or combo?
both, combo w/ metformin or TZD
DPP-IV inhibitor MOA
- block degradation of endogenous incretins, GLP-1 and GIP
- inhibit glucagon release
- increases insulin secretion
benefits of DPP-IV inhibitor
- no hypoglycemia
- well tolerated
* weight neutral
how much do DPP-IV inhibitors lower HbA1c
0.6%
warnings/risks with DPP-IV inhibitors
- pancreatitis
- joint pain
- saxagliptin can worse HF
what does SGLT-2 inhibitor stand for
- Sodium glucose CoTransporter inhibitors
SGLT-2 inhibitor examples
- Canagliflozin / Invokana
2. empagliflozin / jardiance
SGLT-2 inhibitor MOA
block resorption of glucose in kidneys
limitation of SGLT-2 inhibitors
not effective if eGRF <45
benefits of SGLT-2 inhibitors
- some weight loss
- may reduce BP
- no hypoglycemia
who are SGLT-2 inhibitors good for
add on therapy for patients who have greater risk of stroke and heart attack
SGLT-2 inhibitors SE
- UTI, yeast infections, increased urination
- increased LDL
- fractures
- possible ketoacidosis
- amputations (invokana)
- hypotension
- bladder cancer? (farxiga)
insulin indications
DM type 1 and 2
gestational diabetes
insulin examples
- short acting insulin - insulin R
- intermediate acting insulin - NPH insulin, lente
- long acting insulin - insulin ultralente
long acting insulin features
- 25 hour half life
- up to 42 hour glucose lowering effect
- relatively peakless
- anytime dosing
insulin MOA
- promotes uptake of glucose by cells
- increased glycogen deposition in liver and muscle
- liver: inhibits synthesis of glucose
- muscle: facilitates uptake of amino acids in –> protein synthesis
- adipose: promotes synthesis of triglycerides and inhibits lipolysis
insulin SE
- hypoglycemia
- lipodystrophy
- edema
Presentation of hypoglycemia
- sweating
- tachycardia
- tremor
- weakness
- hunger
- blurred vision
- confusion
- convulsions
- coma
Glucagon indications
- refractory hypoglycemia (after PO or IV glucose)
- hyperinsulin states - insulin overdose, insulinoma
- drug overdoses - beta blockers, ca channel blockers
- intestinal relaxation
Glucagon CIs
- pheochromocytoma
Glucagon SE
- nausea/vomiting
- hyperglycemia
- hypokalemia
Combination drugs
- invokamet = canagliflozin + metformin
- synjardy = empagliflozin + metformin
- glyxambi = empagliflozin + linagliptin