Diabetes Treatment Flashcards
treatment of diabetes mellitus - general principles
*all pts with DM should receive education on diet, exercise, blood glucose monitoring, and complication management
*pts with T1DM will all require insulin therapy
*pts with T2DM: threshold varies clinically, but generally A1c < 7.5% in asymptomatic pt, start with lifestyle changes before medical therapy
treatment of diabetes mellitus - goals of tx
*goal 1 = restore euglycemia (HbA1c of 7.0% or less)
-adjusted based on patient’s age, risk of hypoglycemia, comorbidities
*goal 2 = reduce complications associated with uncontrolled blood sugars
glucose monitoring
*HbA1c is measured every 3 months
*glucose monitoring by the patient is needed for more immediate feedback:
1. fingerstick checks
2. continuous glucose monitors
*generally, aim for blood glucose between 70-180 mg/dL the majority of the time
insulin therapy - overview
*essential for treatment of T1DM
*can also be used for T2DM and gestational diabetes, when needed
insulin therapy - MOA
*same as endogenous insulin; binds insulin receptor (tyrosine kinase activity):
1. stimulates cellular uptake of glucose
2. liver: stores glucose to glycogen
3. muscle: increase glycogen & protein synthesis
4. fat: increases triglyceride storage
5. cell membrane: increase K+ uptake (shift K+ into cells)
insulin - metabolism/excretion
*renally excreted
*will remain long in the body/have longer lasting effects in pts with CKD/ESRD
rapid acting insulin products
*lispro, aspart, glulisine
*onset = 5-15 min
*peak = 30-90 min
*duration = 4 hr
*a type of bolus insulin (given at mealtime)
short acting insulin products
*regular insulin
*onset = 30-60 min
*peak = 2-3 hrs
*duration = 5-8 hrs
*a type of bolus insulin (given at mealtime)
basal (long-acting) insulin products
*detemir, glargine, degludec
*onset = 2 hrs
*peak = no peak; basal control
*duration = 20-24 hours
*acts as our background insulin (baseline insulin present to cover gluconeogenesis from liver when fasting)
example insulin regimen
*glargine (long-acting basal insulin) 30 units once daily AND lispro (rapid-acting bolus insulin) 10 units 3x daily before meals
note - rapid and short-acting insulin should be administered 15 min before meals due to time of onset
insulin therapy - ADEs
1. hypoglycemia (most dangerous side effect of insulin; can lead to coma or death if severe)
2. weight gain: increased glucose uptake in muscle & adipose tissue; excess glucose is converted to glycerol and triglycerides → weight gain
3. lipohypertrophy: repeated insulin injections in same site → lumps of scar tissue
glucagon therapy - overview
*should always be prescribed with insulin
*administered when pt is having hypoglycemia and unable to tolerate oral glucose (unconscious, vomiting, etc)
*MOA: works by rapidly increased glycogenolysis
*also has antagonist effects on glucose uptake by liver cells and increases gluconeogenesis
*injectable or nasal spray formulations
metformin - indications, MOA
*indication: commonly first line for T2DM
*MOA: enhances cellular glucose uptake (induces GLUT-4 expression), reduce liver gluconeogenesis and intestinal glucose absorption
metformin - advantages & disadvantages
*pros: weight loss, lower LDL, lower triglyceride levels, lower BP, low risk for hypoglycemia, improves cardiovascular risk
*cons: nausea, diarrhea, metallic taste, LACTIC ACIDOSIS (caution/do not use in CKD, severe CHF, liver disease)
thiazolidinediones (TZD) - examples, indications, MOA
*pioglitazone, rosiglitazone
*second or third line DM treatment
*indication: used to intensify therapy
*MOA: increase insulin sensitivity by activating a group of nuclear receptors (PPAR-gamma); the cell stores fatty acids (making these less available for energy use) so is forced to use glucose instead, which lowers glucose levels
thiazolidinediones (TZD) - advantages & disadvantages
*pioglitazone, rosiglitazone
*pros: mild GI side effects, can be used in CKD
*cons: fluid retention, heart failure, liver damage, decreased bone density, bladder cancer
GLP-1 agonists - examples, indications, MOA
*semaglutide, dulaglutide, liraglutide, exanatide
*aka incretin mimics
*indication: can be first or second line for DM
*MOA: bind to GLP-1 receptor and mimic endogenous GLP-1; increased glucose-dependent insulin release
-GLP-1 is an incretin hormone secreted by intestinal cells after a meal
-causes increased postprandial insulin secretion, decreased glucagon delay, delayed gastric emptying, increased satiety
GLP-1 agonists - advantages
*weight loss
*reduce cardiac events
*renal protection in CKD
*rare hypoglycemia
GLP-1 agonists - disadvantages
*mostly come in injectable forms
*GI upset
*contraindication in MEN2a or 2b/medullary thyroid cancer
*relative contraindication in pancreatitis
DPP-4 inhibitors - examples, indication, MOA
*sitagliptin, saxagliptin, linagliptin
*indication: second line for DM
*MOA: bind to and inactivate the enzyme DPP-4
-DPP-4 degrades GLP1, so these medications increase endogenous levels of GLP-1
*effects are similar to GLP-1 agonists, but much less potent
*no hypoglycemia, generally few side effects
sulfonylureas - examples, indications
*glipizide, glyburide, chlorpropamide, tolbutamide
*indications: historically first line, rarely used now
sulfonylureas - MOA
*glipizide, glyburide, chlorpropamide, tolbutamide
*MOA: stimulate pancreatic insulin release by closing ATP-sensitive potassium channels in the beta cell plasma membrane → depolarizes the cell → influx of calcium → INSULIN RELEASE INDEPENDENT OF FOOD INTAKE (higher risk of hypoglycemia)
sulfonylureas - pros and cons
*pros: cheap
*cons: high risk of hypoglycemia (insulin release is stimulated despite glucose status), early onset dementia in geriatric pts, weight gain
*use with caution in elderly and pts with CKD
SGLT2 inhibitors - examples, indications
*canagliflozin, empagliflozin, dapagliflozin
*indication: second line DM treatment (can be first line depending on presence of CHF, CKD)
SGLT2 inhibitors - MOA
*canagliflozin, empagliflozin, dapagliflozin
*MOA: inhibit glucose reabsorption in the proximal tubule by blocking SGLT2 transporters → increased urinary excretion of glucose
SGLT2 inhibitors - pros and cons
*pros: secondary prevention of CV events, renal protection in CKD
*cons: UTI, dehydration, genital candida infections, hypoglycemia, AKI, euglycemic DKA
other non-insulin medications that could be used in diabetes
*repaglinide
*pramlintide
*alpha-glucosidase inhibitors (acarbose); ADEs = bloating and flatulence
