Diabetes Mellitus Management, part 2 Flashcards
3 Common indications for insulin
- Standard of care in T1DM
- Often useful in longstanding or refractory T2DM
- Tx of hyperglycemic crises states (DKA, HHS)
Insulin is Classified by ___ and ___
time to onset
duration of action
what type of insulin may have less-than-ideal timing but are also less expensive
Non-analog insulins (regular, NPH)
SE of insulin
- Hypoglycemia
- wt gain
- Injection-site reactions
- Inflammation
- Fibrosis
- Pain
- Lipohypertrophy
- Lipoatrophy
what substance often causes hypoglycemia in insulin-dependent patients
alcohol
Insulin dosing requirements
- generally 0.5 U/kg
- 50% = “background”/long-acting insulin (basal)
- 50% = cover meals consumed during the day (bolus)
pros vs cons of inhaled insulin
- Pro - rapid-acting insulin that does not have to be injected
- Con - not for use in smokers or pts with chronic lung conditions
SE of inhaled insulin
cough
possible increased risk of lung cancer (requires periodic PFTs)
pros vs cons of Premixed insulins
- pro - combines long-acting and short-acting insulin (fewer injections)
- con - less ability to adjust dosage
- Most forms use NPH, which can be harder to predict
- New form (insulin aspart/insulin degludec) - expensive
Shorter duration of action for insulin = ____ number of doses needed per day
increased
what are the bolus insulins
- rapid-acting
- lispro (Humalog) / Insulin lispro-aabc (Lyumjev)
- Insulin aspart (Novolog) / Insulin faster aspart (Fiasp)
- Insulin glulisine (Apidra) - rapid-acting, inhaled
- Technosphere insulin (Afrezza) - SA
- Human regular (Humulin R, Novolin R)
what are the basal insulins
- intermediate-acting
- Human NPH (Humulin N, Novolin N) - Long-Acting
- Insulin detemir (Levemir)
- Insulin glargine U100 (Lantus)
- Insulin glargine U300 (Toujeo) - ultra-long
- Insulin degludec (Tresiba) ultra-long
Insulin ways of Administration
- Insulin Syringes/Needles
- 0.3 mL, 0.5 mL, 1 mL (often marked in U)
- Ultrafine needles (31 or 33 g) - reduce pain of injection
- Various lengths of needles - 6 mm, 8 mm, 12.7 mm - Insulin Pens
- Pre-filled, convenient, disposable pens
- Easy adjustable dosing
- ultrafine needles (31 or 33 g) in varying lengths - Insulin Pumps
- continuous insulin infusion
- High risk of hypoglycemia
which insulin administration is Primarily used for T1DM pts who are reliable about BG monitoring and self-management
Insulin Pumps
injection sites for insulin
- upper outer arms
- abdomen
- buttocks
- upper outer thigh
Recommended to stick to a given area for consistent absorption, but to rotate to avoid injection site reactions (e.g. lipohypertrophy)
Used to help with portion control and insulin bolus dosing
Carbohydrate Counting
Typically individualized for pt with dietitian
Depending on his/her nutrition goals, weight, BG goals, etc.
Common starting guidelines for carb counting
Males - 60 g per meal, 30 g per snack
Females - 45 g per meal, 15 g per snack
which insulin preparation
onset: <15 minutes
Peak action: Dual; (2-3 hrs; several hrs later)
effective duration: 10-16 hours
Intermediate + Rapid-Acting
which insulin preparation
onset: 30 min
peak action: varies (2-3 hrs; several hrs later)
effective duration: 10-16 hrs
intermediate + short-acting
which insulin preparation
onset of action: <15 mins
peak actions: varies
effective duration: +24 hr
long-acting + rapid-acting
Dawn Phenomenon and Somogyi Effect both present as ___ in the AM (fasting glucose reading)
hyperglycemia
- Nocturnal release of counterregulatory hormones (glucagon, epinephrine, cortisol) leads to increased glucose levels
- Inadequate levels of insulin to balance increased glucose leads to AM hyperglycemia
- due to body’s natural response to fasting overnight
what is this effect called?
Dawn Phenomenon
“Down Insulin”
- Patient becomes hypoglycemic while asleep
- Body responds appropriately by releasing counterregulatory hormones
- Increased glucose levels leads to AM “rebound” hyperglycemia
- due to excess amounts of exogenous insulin with evening dose
what is this effect called?
Somogyi Effect
“So Much Insulin”
How to tell the difference between Dawn Phenomenon and Somogyi Effect
- check sugar at 3 am
- Low readings - Somogyi Effect
- Medium-high readings - Dawn Phenomenon - Alternative - decreasing PM dose of insulin
- Hyperglycemia improves - Somogyi Effect
- Hyperglycemia persists or worsens - Dawn Phenomenon
management for somogyi effect
↓ evening/bedtime insulin dose, add bedtime snack if needed
If you aren’t sure - don’t increase insulin dose!
management for dawn phenomenon
↑ evening and/or bedtime insulin dose
If you aren’t sure - don’t increase insulin dose!
what are the 3 common insulin dosing regimen
- Once-daily basal insulin - MC T2DM
- Twice-daily mixed insulin
- Basal-bolus insulin
which insulin regimen
Mimics natural release of insulin
Requires 4 injections/day (3 rapid-acting or short-acting, 1 long-acting)
Requires 3-4 BG checks/day
Physiologic (Basal/Bolus)
dosing for Physiologic (Basal/Bolus)
- Starting calculation of 0.5 U/kg - divided into two portions
- 50% - basal (long-acting) insulin dose
- 50% - bolus (rapid-acting or short-acting) - divided into 3 equal parts - Alternative - carb-counting for bolus dosing
- 1 U per 15 g of carbohydrate, PLUS
- 1 U for every 50 mg/dL of BG at pre-meal screening above a set goal (i.e., 120 mg/dL) - Adjust pending blood sugar results
which insulin type
More predictable absorption
Closer to endogenous insulin release pattern
Convenient (QD) dosing
Less hypoglycemia
Long-acting (e.g., Lantus)
which Long-acting insulins are thought to have least hypoglycemia compared to other LA insulins
Toujeo and Tresiba > Lantus/Levemir
which insulin type
Less predictable absorption
BID dosing
Intermediate-acting (NPH)
which insulin is > NPH insulin for basal
LA insulin
what type of insulin > regular insulin for bolus
rapid-acting
which insulin type
More predictable absorption
Closer to the body’s release of endogenous insulin
Shorter duration of action - less “leftover” hypoglycemia
Rapid-acting
which insulin type
Less predictable absorption
Similar dosing to rapid-acting (i.e., no advantage)
Regular
which insulin regimen
- Requires 2 injections/day
- Formulations with rapid-acting preferred over short-acting
- Long-acting may be better than intermediate-acting; limited data - Requires 2-3 BG checks/day
- Dosing - estimate equal division of daily insulin requirements
BID Premixed Dosing
which insulin regimen
1. Typically used with regular insulin
2. Not preferred, but often still used,
esp in inpatient
- Reactive approach to hyper- and hypoglycemia
- Often results in wide swings in glucose control
3. Does not address basal insulin needs
- May be used along with a basal insulin
Sliding-Scale Insulin
NOT a proactive drug, more reactive
Major Categories of Non-Insulin DM Meds
- Insulin Sensitizers
- Insulin Secretagogues
- Glucose Absorption Inhibitors
- Incretin-Based Therapies
- Amilyn-Based Therapies
- Miscellaneous
- Bile acid sequestrants
- Dopamine receptor agonists - Combo Drugs
Biguanides
Insulin Sensitizers
Thiazolidinediones
Insulin Sensitizers
Sulfonylureas
Insulin Secretagogues
Meglitinides
Insulin Secretagogues
Alpha-glucosidase inhibitors
Glucose Absorption Inhibitors
SGLT2 inhibitors
Glucose Absorption Inhibitors
GLP-1 receptor agonists
Incretin-Based Therapies
DPP-4 inhibitors
Incretin-Based Therapies
Amylin analogs
Amilyn-Based Therapies
Metformin (Glucophage)
Biguanides
- Helps “fix a leaky liver”
- Inhibits hepatic gluconeogenesis
- Helps decrease intestinal absorption of glucose
- Slightly improves insulin sensitivity
- Increases glucose uptake and utilization by peripheral tissue
what is this drug
Biguanides (Metformin)
First-line therapy in patients with T2DM!
Biguanides (Metformin)
advantages of Biguanides (Metformin)
- Glucose - Improves both FBG and PPBG
- Not associated with hypoglycemia - Cost - Inexpensive and well-studied
- Wt - wt loss (2-5 kg) or wt-neutral
- Lipids - improves lipid profile, in particular TGs
disadvantages of Biguanides (Metformin)
- GI side effects - anorexia, metallic taste, N/V/D
- B12 deficiency
- Lactic acidosis - rare; black box warning
- Avoid in pts with CRF, liver failure, or excess ETOH intake
when do you have to temporarily d/c biguanides (metformin)
- acute severe illness (hospitalized)
- dehydrated
- has CHF
- exposed to radiocontrast media
If kidney or liver is bad, avoid metformin bc it can cause Lactic acidosis - black box warning
CI for Biguanides (Metformin)
- Allergy to rx
- Acidosis
- CKD - Serum Cr of 1.4+ (F)/1.5+ (M)
- GFR <30 mL/min (previously <60) - CHF, hospitalization, radiocontrast
Rosiglitazone (Avandia)
Thiazolidinediones
Pioglitazone (Actos)
Thiazolidinediones
which insulin medication class
1. “Unlock” muscle and fat cells to help them utilize glucose
- Improves insulin sensitivity
— Increases glucose uptake and utilization by peripheral tissue
- Decreased gluconeogenesis
- Increased adipogenesis
Thiazolidinediones
TZD MOA
Bind a nuclear receptor called PPAR-gamma, which affects the expression of several genes relevant to glucose metabolism!
advantages of TZD
- Glucose - Improves both FBG and PPBG
- Not associated with hypoglycemia - Lipids - pioglitazone improves HDL, TG
- Insulin - lower requirements
disadvantages of TZD
- Weight - weight gain
- Edema - peripheral edema, macular edema, CHF
- Bladder cancer - pioglitazone increases risk
- Lipids - rosiglitazone worsens TC, LDL, increases HDL
-
CV - black box warnings
- Both carry BBW for CHF - Fracture risk
- Anemia
which TZD specifically also carries a BBW for MI
Rosiglitazone
Caution and CI of TZD
Caution:
1. Osteoporosis risk
2. Liver disease
CI:
1. Allergy to rx
2. CHF
Glimepiride (Amaryl)
Sulfonylureas
Glipizide (Glucotrol)
Sulfonylureas
Glyburide (DiaBeta, Micronase)
Sulfonylureas
Repaglinide (Prandin)
Meglitinides
Nateglinide (Starlix)
Meglitinides
what type of medications “Zap” the pancreas to stimulate increased production of insulin
Sulfonylureas
Meglitinides
MOA of Sulfonylurea/Meglitinide
Bind to a site on the ATP-sensitive K+ channel of beta cells, leading in turn to depolarization, opening of voltage dependent Ca channels, and release of insulin
advantages of Sulfonylureas / Meglitinides
- Glucose - Improves both FBG and PPBG
Greater effect on FBG - Cost - Inexpensive (esp sulfonylureas)
- Time - Short onset of action
disadvantages of Sulfonylureas / Meglitinides
- hypoglycemia
- wt gain
- Dosing - TID with meglitinides
- Metabolism -pts with chronic liver disease or chronic renal failure may be poor candidates
- Liver - cannot metabolize rx
- Renal - cannot excrete rx/metabolites
cautions and CI of Sulfonylureas / Meglitinides
CI:
1. Allergy to rx or to sulfa drugs
2. Diabetic ketoacidosis
Cautions:
1. Liver/Renal Disease (CI in Canada)
2. Major CV disease
Acarbose (Precose)
α-Glucosidase Inhibitors
Miglitol (Glyset)
α-Glucosidase Inhibitors
what insulin med class
“Block” the breakdown of starches in the intestine
Competitively inhibit enzymes that digest starch and sucrose
Delayed carb absorption
↓ postprandial glucose rise
α-Glucosidase Inhibitors
advantage of α-Glucosidase Inhibitors
Glucose - Improve PPBG
- Not associated with hypoglycemia
disadvantages of α-Glucosidase Inhibitors
- GI - flatulence, elevated LFTs
- Glucose - may increase hypoglycemia
risk if given with sulfonylureas or insulin - Dosing - TID
caution and CI of α-Glucosidase Inhibitors
Caution:
1. CKD
2. Liver disease
CI:
1. Allergy to rx
2. Diabetic ketoacidosis
3. Cirrhosis
4. Major chronic GI disease
- Inflammatory Bowel Disease
- Colonic ulceration
- Intestinal Obstruction
- Any other GI disease that would worsen as a result of increased gas formation
Canagliflozin (Invokana)
SGLT2 Inhibitors
Dapagliflozin (Farxiga)
SGLT2 Inhibitors
Empagliflozin (Jardiance)
SGLT2 Inhibitors
Ertugliflozin (Steglatro)
SGLT2 Inhibitors
which insulin med class
“Halt” renal glucose reabsorption
↑ glucose excretion by inhibiting protein that accounts for about 90% of glucose reabsorption in the kidney
Act on the proximal tubule
SGLT2 Inhibitors
advantages of SGLT2 Inhibitors
- Glucose - Lower glucose independently of insulin
- Not associated with hypoglycemia - weight loss (2-5 kg)
- lower blood pressure
- Proteinuria - can improve CKD even in non-DM pts
disadvantages of SGLT2 Inhibitors
- GU - ↑ incidence of UTIs, genital mycotic infections
- ↑ LDL
- ↓ efficacy if low GFR
- can cause ↑ serum creatinine and ↓GFR - CV - intravascular volume contraction, dehydration, and hypotension
- Ketoacidosis - May mask DKA
- Other Concerns
- dapagliflozin - breast, bladder cancer
- canagliflozin - bone fractures, amputations
cautions and CI of SGLT2 Inhibitors
CI:
1. Allergy to rx
2. Moderate-severe CKD
Caution:
1. Osteoporosis risk
2. Mild CKD
3. Limited long-term clinical data
Exenatide (Byetta/Bydureon)
GLP-1 Receptor Agonists
Liraglutide (Victoza, Saxenda)
GLP-1 Receptor Agonists
Lixisenatide (Adlyxin)
GLP-1 Receptor Agonists
Dulaglutide (Trulicity)
GLP-1 Receptor Agonists
Semaglutide (Ozempic, Rybelsus*)
GLP-1 Receptor Agonists
Tirzepatide (Mounjaro)**
GLP-1 Receptor Agonists
what insulin med class
“Mimic” the incretin GLP-1
GLP-1 Receptor Agonists
advantages of GLP-1 Receptor Agonists
- Glucose - Improves both FBG and PPBG
- Not associated with hypoglycemia - Weight - associated with weight loss; decreased appetite
disadvantages of GLP-1 Receptor Agonists
- Dosing - SC injection (except Rybelsus)
- Varies from BID to once weekly dose - Glucose - May cause hypoglycemia if patient is also taking insulin secretagogues
- GI - N/V /D - dose-dependent
- ↑ GI SE but ↑ weight loss and ↓ BG with tirzapetide - Pancreatitis
-
Thyroid cancer - BBW
- Increased incidence of C-cell neoplasia and medullary thyroid cancer in rats - Cost - May be expensive
CI and caution of GLP-1 Receptor Agonists
- Allergy to rx
- PMHx or FMHx of medullary thyroid carcinoma or MEN2
Caution - gastroparesis, use with other rx that ↓ GI motility
Sitagliptin (Januvia)
DPP-4 Inhibitors
Sitagliptin (Januvia)
DPP-4 Inhibitors
Saxagliptin (Onglyza)
DPP-4 Inhibitors
Linagliptin (Tradjenta)
DPP-4 Inhibitors
Alogliptin (Nesina)
DPP-4 Inhibitors
what insulin med class
“Stretch” out the effects of endogenous incretin GLP-1 by inhibiting the enzyme that degrades it
DPP-4 Inhibitors
advantages of DPP-4 Inhibitors
- Glucose - Improves both FBG and PPBG
- Not associated with hypoglycemia - weight neutral
disadvantages of DPP-4 Inhibitors
- GI - N/V/D - less than GLP-1 agonists
- HEENT - nasopharyngitis, URI
- Cost - may be expensive
- Pancreatitis
- Hypersensitivity - urticaria, angioedema
-
Special alerts
- Alogliptin and Saxagliptin have an alert for
possible increased risk of heart failure
- All have an alert for possible increased risk
of severe arthralgias
Pramlintide (Symlin)
Amylin Analogs
low efficiacy
which insulin med class “Impersonate” the effects of amylin (synthetic amylin analog)
Amylin Analogs
advantages of Amylin Analogs
- Glucose - Improves both FBG and PPBG
- Weight - weight loss
- Use - may be used in T1DM or T2DM
disadvantages of amylin analogs
- Dose - must be given as SC injection
- Glucose - may cause hypoglycemia when used with insulin
- BBW - GI - N/V, anorexia
- Contraindications
- Allergy to rx
- Gastroparesis
- Unawareness of hypoglycemia - Caution
- Other rx that ↓ GI motility
Colesevelam (Welchol)
Bile Acid Sequestrants
Lowers A1c 0.3-0.5%
Also helps reduce LDL
SE - constipation, dyspepsia, ↑ TG
Bromocriptine (Parlodel, Cycloset)
Dopamine Receptor Agonists
Lowers A1c 0.1-0.5%
SE - N/V, dizziness, HA
what are the Combination Medications - Injection
- Long-acting insulin + GLP-1 agonists
- Soliqua - Insulin glargine (Lantus) + lixisenatide (Adlyxin)
- Xultophy - Insulin degludec (Tresiba) + liraglutide (Victoza)
Max doses due to GLP-1 agonist component
- May not be enough insulin for poorly controlled diabetics
Management - Type I Diabetes Mellitus
- Insulin
- Recommended methods:
- Multiple-dose injection therapy (Basal-bolus regimen)
- Continuous subcutaneous insulin infusion (insulin pump) - in appropriate pts - Adjunct pharm tx
- Pramlintide - not strongly recommended
- Metformin, GLP-1s, DPP-4s, and SGLT2 inhibitors have been studied but currently are NOT approved to treat T1DM* - Be sure to:
- Match prandial (bolus) insulin to carb intake, anticipated activity level, and pre-meal insulin
- Use analog insulins (instead of human insulins) for ↑ predictability and ↓ hypoglycemia
- Consider a pump with a sensor to suspend insulin infusion in pt with frequent nocturnal hypoglycemia or hypoglycemia unawareness
- Consider use of a continuous glucose monitor if available
what hypoglycemia med
mimics the effects of endogenous glucagon
↑ hepatic glycogenolysis and gluconeogenesis
Glucagon
what hypoglycemia med
provides body with monosaccharide fuel for metabolic processes
Dextrose
SE and CI of dextrose
SE: hyperosmolar syndrome, hypokalemia, dehydration, edema
CI: Allergy to rx or to corn; diabetic coma; CNS hemorrhage; severe dehydration; DTs
weight Management - Type II Diabetes Mellitus
- Wt Loss
- Caloric restriction, increased exercise, behavior modification
- Consider use of appetite suppressants and/or bariatric surgery if needed
- Sufficient weight loss can actually enable patients to discontinue DM meds!
- Nonobese patients - encourage exercise to reduce visceral adiposity
at diagnosis management for T2DM
metformin + diet + exercise
If A1c not at goal in 3 mo, how would T2DM management change
- metformin + another agent + diet + exercise
- metformin + two other agents + diet + exercise
- metformin + insulin +/- other agents + diet + exercise
when to consider insulin therapy for T2DM
- markedly elevated A1c (9.0% or higher)
- significant hyperglycemia s/s
how to choose a medication for T2DM management
- Efficacy - DPP-4 considered “moderate”; all others are considered “high”
- Hypoglycemia - risk with sulfonylureas, meglitinides, pramlintide, insulin
- Weight effects
- Loss - GLP-1 agonists and SGLT2 inhibitors, Pramlintide
- Neutral - Metformin, DPP-4 inhibitors
- Gain - Sulfonylureas, TZDs, insulins - Cost - metformin, sulfonylureas, and TZDs = most affordable
- Major SE - consider comorbidities and areas of risk
