Chidiebere Eze, PharmD

PGY-1 pharmacy resident

IUH – Ball Memorial Hospital

Diabetes
Diagnosis:
Non-diabetes Pre-diabetes Diabetes
Random plasma glucose - - >200 mg/dL
Fasting plasma glucose 70-110 mg/dL 100-125 mg/dL ≥126mg/dL
2 hour OGTT with 75 gm of carbohydrate <140 mg/dL 140-199 mg/dL ≥200 mg/dL
A1c 4-6% ADA: 5.7-6.4% ≥6.5%
AACE: 5.5-6.4%

Treatment goals:
ADA recommendation AACE recommendation
Fasting or preprandial glucose 80-130 mg/dL <110 mg/dL
Postprandial glucose <180 mg/dL <140 mg/dL
A1c* ≤7% ≤6.5%
*Exception: goal A1c of ≤8% in the elderly

Lifestyle management with clinical benefit:

 Weight loss: 2-8 kg
o Diet: choosemyplate.org (grains, fruits, vegetables, protein, dairy)
o Physical activity: 150 minutes of moderate activity per week
 Alcohol: use in moderation – women (1 drink), men (2 drinks)
o Can cause delayed hypoglycemia
 Vitamins and supplements

Laboratory monitoring:
 Self-monitoring blood glucose: Basal/Bolus (multiple times/day); Basal/Oral medications: No clear recommendation
 A1c: every 3 months (if not at goal), every 6 months (if at goal)
 Fasting lipid panel: baseline and as indicated
 Liver function tests: baseline and annually
 Microalbumin/creatinine ratio: annually
 Serum creatinine: baseline and annually
 TSH: perhaps in dyslipidemia and women >50 years

Types of diabetes:
 Type 1:
o “Juvenile-onset diabetes”. Autoimmune disease: body attacks beta cells and destroys its ability to make insulin
o Common in children or adolescents
o Treatment: Insulin (injections/pumps)
 Type 2:
o Insulin resistance
o Usually in adults
o Treatment: Lifestyle modifications, insulin and oral agents

Treatment options:
• Biguanides: Metformin (Glucophage)
• Glucagon-Like Peptide-1 Agonists (GLP-1 agonists):
• Sodium-glucose Cotransporter-2 inhibitors (SGLT2i):
• Dipeptidyl Peptidase-4 inhibitors (DPP4i):
• Thiazolidinediones (TZDs):
• Sulfonylureas (SU):
• Meglitinides (GLN):
• Alphaglucosidase inhibitors:
• Others
 Chidiebere Eze, PharmD
PGY-1 pharmacy resident
IUH – Ball Memorial Hospital
 Biguanides: Metformin (Glucophage); Metformin XR (Glumetza, Fortamet)
o MOA:
 Inhibits hepatic glycogenolysis and gluconeogenesis (↓ glucose production and absorption)
 ↑ insulin sensitivity in muscle and fat
o Dose:
 Initial: 500 mg BID, can titrate up after tolerating 5-7 days of steady dose; Target: 2000 mg daily
o Benefits/Considerations:
 Weight neutral
 May reduce cardiovascular disease, mortality and microvascular complications
 Cost effective
 Lowers A1c by 1-1.5%
 Targets FBG and considered for pre-diabetes
o Adverse reactions:
 GI distress (titrate dose to avoid), consider XR formulation or bulk-forming laxative to reduce diarrhea
 Lactic acidosis (esp. with alcohol use, uncontrolled COPD and HF)
o Warnings/precautions:
 Iodinated contrast (nephrotoxic), Vit B12 Deficiency
 Ghost tablet with XR formulation
o Renal adjustments:
 C/I with sCr >1.5♂ and >1.4♀ or GFR <30

 GLP-1 receptor agonists: Liragluitide (Victoza), Exenatide (Byetta, Bydureon), Dulaglutide (Trulicity), Albiglutide (Tanzeum),
Lixisenatide (Adlyxin)*
o MOA
 Long acting analog of an incretin hormone:
 ↑ insulin secretion and B-cell growth, ↓glucagon secretion and food intake
 Slows gastric emptying (feeling full) that can lead to eating less food and then weight-loss
o Dose:
GLP-1 agonist ~A1c decrease Weight loss Dosing frequency Notes
Albiglutide (Tanzeum) 1% 1 kg 30 mg SQ weekly Low A1c and weight loss
MAX: 50 mg
Exenatide (Byetta) 1% 2 kg 5 mcg SQ BID Increased administration frequency
MAX: 10 mcg Avoid in CrCl<30 mL/min
Exenatide ER (Bydureon) 1.5% 2.5 kg 2 mg SQ weekly Large needle, more inj site reactions
Avoid in CrCl<30 mL/min
Dulaglutide (Trulicity) 1.5% 2.5 kg 0.75 mg SQ weekly
MAX: 1.5 mg
Liragluitide (Victoza)* 1.5% 2.5 kg 0.6 mg SQ daily Daily frequency
MAX: 1.8 mg
* Also has a once weekly formulation: Liraglutide (Saxenda), approved only for weight loss

o Benefits/Considerations:
 Weight loss
 Expensive injection ($300 - $500 per month); also patient education is needed
 Lowers A1c by 1-1.5%
 Targets FBG and post PPG
 Don’t recommend in patients with gastroparesis
o Warnings/Precautions
 Risk of thyroid C-cell tumors (dose and duration dependent, esp Victoza),
 Acute pancreatitis
o Adverse effects
 GI, slow gastric emptying (N/V/D)
o Renal Adjustments
 Caution in moderate impairment and not recommended in severe impairment, but no specific dose adjustments
 Chidiebere Eze, PharmD
PGY-1 pharmacy resident
IUH – Ball Memorial Hospital
 SGLT2 inhibitors: Canagliflozin (Invokana), Dapagliflozin (Farxiga), Empagliflozin (Jardiance)
o MOA:
 Reduces glucose reabsorption from the proximal renal tubule in the kidneys
o Dose:
SGLTi Dose Renal adjustment Hepatic adjustment
Canagliflozin (Invokana) 100 mg daily Avoid if GFR <45 mL/min) Avoid if Child Pugh Class C
MAX: 300 mg (if GFR >60)
Dapagliflozin (Farxiga) 5 mg daily Avoid if GFR <60 mL/min)
MAX: 10 mg
Empagliflozin (Jardiance) 10 mg daily Avoid if GFR <45 mL/min)
MAX: 25 mg
o Benefits/Considerations:
 Lack of hypoglycemia
 Weight loss
 Blood pressure reduction, cardiovascular benefit (Invokana)
 Lowers A1c by 0.5-1%
 Targets FBG
 Expensive ($340/month)
o Warnings/Precautions:
 Euglycemic DKA (without elevated BG due to glucose wasting through the kidneys)
o Adverse effects:
 Hyperkalemia, Hypotension, UTI, Genital mycotic infections (increase risk in uncircumcised males)
 Recent reports of increased fracture/bone loss, bladder cancer (Farxiga), stroke (Invokana)
o Renal Adjustments
 Dependent on kidney function – so wont work if kidneys don’t work (ineffective in severe kidney disease)

 DPP4 inhibitors: Alogliptin (Nesina), Linagliptin (Tradjenta), Saxagliptin (Onglyza), Sitagliptin (Januvia)
o MOA:
 ↑ glucose dependent insulin secretion (decreases degradation of endogenous incretin)
 ↓ glucose dependent glucagon secretion
o Dose:
DPP4 inhibitors Dose Renal adjustment
Alogliptin (Nesina) 25 mg daily CrCl: 30-60 mL/min: 12.5 mg daily
CrCl: <30 mL/min or HD: 6.25 mg daily
Linagliptin (Tradjenta) 5 mg daily -
Saxagliptin (Onglyza) 2.5-5 mg daily CrCl: <50 mL/min or HD: 2.5 mg daily
Sitagliptin (Januvia) 100 mg daily CrCl: 30-50 mL/min: 50 mg daily
CrCl: <30 mL/min or HD/PD: 25 mg daily
o Benefits/Considerations:
 Weight neutral
 Lack of hypoglycemia
 Well tolerated oral medication
 Lowers A1c by 0.5-1%
 Targets post PPG
 Expensive: ~$300/month
o Warnings/Precautions
 Upper respiratory tract infection, hypoglycemia (Onglyza), hepatotoxicity
 New concern for use in patient with HF (Onglyza, Nesina) or joint pain (arthralgia)  consider d/c
 Avoid use in patients with pancreatitis
o Adverse effects
 GI, nasopharyngitis
o Renal adjustments:
 Needed in all except in Tradjenta
 Chidiebere Eze, PharmD
PGY-1 pharmacy resident
IUH – Ball Memorial Hospital
 Thiazolidinediones (TZDs): Pioglitazone (Actos), Rosiglitazone (Avandia)
o MOA:
 ↑ insulin sensitivity in muscle and fat
 Agonist for peroxisome proliferator-activated receptor-gamma (PPARgamma). Activation of
PPARgamma increases production of genes involved in glucose and lipid metabolism
o Dose:
 Pioglitazone (Actos): 15-45 mg daily
 Rosiglitazone (Avandia): 4-8 mg daily in 1-2 doses
o Benefits/Considerations:
 Weight gain
 Fluid retention (concern in CHF patients)
 Lowers A1c by 1-1.5%
 Targets FBG
o Warnings/Precautions:
 Black Box: HF exacerbation (C/I NYHA class III/IV, do not recommend starting in stable heart disease)
 Fractures, edema, bladder CA (Actos), macular edema
 Avoid using Rosiglitazone if LFT >2.5 ULN
 Increased MI and Cardiac Death (Increased stroke, HF, MI, all cause death with avandia compared to actos)
o Adverse effects:
 Weight gain, ↑ LDL/HDL/TC, HA, URI, dec. TG
 Fluid retention (↑ edema due to PPARgamma cells in renal tubules. Overstimulation leads to fluid retention)
o No renal adjustments

 Sulfonylureas (SU): Glimepiride (Amaryl), Glipizide (Glucotrol), Glyburide (Diabeta, Glynase)

o MOA
 Stimulates pancreatic insulin secretion (↑ insulin production), reduces gluconeogenesis
o Dose:
 Glipizide IR: 5-40 mg daily with meal (split higher doses)
 Glipizide XR: 5-20 mg daily with first meal (max of 10 mg BID)
 Glimepiride 1-8mg daily with first meal
o Benefits/Considerations:
 Weight gain
 Lowers A1c by 1-1.5%
 Targets FBG and post PPG
 Can cause hypoglycemia (consider avoiding in elderly)
 May lose effectiveness overtime (can only bang on pancreas for so long)
o Warnings/Precautions
 Sulfa allergy
o Adverse Effects
 GI distress(bloating, flatulence), Hypoglycemia
o Renal Adjustments
 Beer’s Criteria
 Glyburide not recommend GFR <60
 Glipizide: reducing dose and avoiding ER

 Meglitinides (GLN): Nateglinide (Starlix), Repaglinide (Prandin)

o MOA:
 ↑ insulin secretion
o Dose:
 Nateglinide (Starlix): 60-120 mg TID
 Repaglinide (Prandin): 0.5-2 mg before each meal (can be 3-4 times daily)
o Benefits/Considerations:
 Weight gain
 Risk of hypoglycemia (esp with alcohol use)
 Lowers A1c by 0.5-1.5%
 Avoid with SU, avoid if NPO, caution in elderly
o Adverse reactions
 URI, hypoglycemia, wt gain
 Chidiebere Eze, PharmD
PGY-1 pharmacy resident
IUH – Ball Memorial Hospital
o Renal Adjustments
 None
 Alphaglucosidase inhibitors: Acarbose (Precose), Miglitol (Glyset)
o MOA:
 Slows intestinal carbohydrate digestion/absorption
 Inhibits metabolism of sucrose to glucose
o Dose:
 Acarbose (Precose): 25-100 mg TID
 Miglitol (Glyset): 25-100 mg TID
o Benefits/Considerations:
 Weight neutral
 Lowers A1c by 0.5-1%
 Targets post PPG
 Avoid Miglitol when SCr >2mg/dL
 Titrate. If hypoglycemia occurs give DEXTROSE (pure glucose), not table sugar (sucrose) or candy
 May reduce cardiovascular events
 Cost: $45 Acarbose, $145 Miglitol
o Adverse effects:
 GI distress (flatulence, diarrhea, bloating, abdominal pain)
o Warnings/Precautions:
 C/I in IBD

 Others: Used in unique situations, but generally not recommended due to lack of efficacy, frequent administration, or side effects
o Antilipemic agent (adjunct therapy): Colesevelam (Welchol)
 MOA:
 Bile acid sequestrant. Binds bile in intestines, causing ↑ hepatic production of bile and ↓
gluconeogenesis
 May ↑ incretin levels and ↓ glucose absorption
 Dose:
 3.75 gm QD, 1.875 gm BID
 Benefits/Considerations:
 Lowers A1c by 0.5-1%
 May decrease absorption of other medications
 Adverse effects:
 GI distress
o Dopamine agonist: Bromocriptine (Cycloset)
 MOA:
 Modulated hypothalamic regulation of metabolism and ↑ insulin sensitivity
 May ↓ hepatogluconeogenesis (low dose IR formulation given within 2 hours of awakening is believed
to combat low hypothalamic dopamine levels that can drive hepatic glucose production)
 Dose:
 0.8 mg daily (MAX: 4.8 mg daily, increments of 0.8 mg)
 Benefits/Considerations:
 Lowers A1c by 0.1%
 Doses are lower that those used of parkinson’s disease
 Adverse effects:
 Nausea, dizziness/syncope, fatigue, rhinitis
o Amylin analog injection: Pramlinitide (Symlin)
 MOA:
 Delays gastric emptying and ↓ secretion of glucagon
 Benefits/Considerations:
 Weight loss
 Decreases post PPG
 Reduce insulin dose when added in combination
 Take before meals
 Adverse effects:
 Black-box warning: severe hypoglycemia in insulin users
 Chidiebere Eze, PharmD
PGY-1 pharmacy resident
IUH – Ball Memorial Hospital
 Insulin
o Rapid-acting
 Aspart (Novolog)
 Lispro (Humalog)
 Glulisine (Apidra)
o Short-acting
 Regular (Humulin/Novolin R, U-500)
o Intermediate-acting
 NPH (Humulin N)
o Mixed-insulin
 Novolog 70/30
 Humalog 75/25, Humalog 50/50
o Long-acting (Basal)
 Degludec (Tresiba –U100 & U200)
 Detemir (Levemir)
 Glargine (Lantus –U100, Toujeo –U300)

Product Onset Peak Duration Notes

Rapid acting
Lispro (Humalog) 15-30 min 30-90 min 3-6 hrs Give 15 mins before, or right after meals
Aspart (Novolog) 10-20 min 45 min 3-5 hrs Give 5-10 mins before meals
Glulisine (Apidra) 10-25 min 45 min 4-5 hrs Give 15 mins before meals or 20 mins after meals
Short acting
Regular (Humulin/Novolin R, U-500) 30-60 min 2-5 hrs 5-8 hrs Give 30 mins before meals. Risk of hypoglycemia!
Intermediate-acting
NPH (Humulin N) 1-2 hrs 4-12 hrs 4-24 hrs Cloudy appearance. Risk of hypoglycemia!
Novolin N lasts for 42 days at room temperature
Long-acting
Detemir (Levemir) 3-4 hrs 3-9 hrs 6-23 hrs
Glargine (Lantus –U100, Toujeo –U300) 3-4 hrs n/a Up to 30 hrs
Degludec (Tresiba –U100 & U200) 42 hours Lasts for 8 weeks at room temp
Can give doses 8 hours apart

Pearls:
 When converting from NPH to Lantus: decrease dose by 20% (and vice versa- increase by 20%)
o Create conversion table
 Insulin + oral agents
o Stop TZDs, insulin secretagogues, SUs
 Chidiebere Eze, PharmD
PGY-1 pharmacy resident
IUH – Ball Memorial Hospital

Hypoglycemia: BG <70 mg/dL

 Treatment:
o Eat 15 g carbs (OJ, regular soda, candy, glucose tabs)
o Wait 15 mins
o Retest
 if >70 mg/dL: eat meal/snack with long acting sugar – protein within next hour
 If <70 mg/dL: repeat cycle
 Adjusting insulin:
o If BG <70 mg/dL: reduce insulin TDD by 10-20%
o If BG <40 mg/dL: reduce insulin TDD by 20-40%

Vaccinations:
 Annual influenza vaccine
 Pneumococcal:
o PPSV23 for ≥2 years of age
o PCV13 (adults, before PPSV23 6-12 months after)
 Hep B:
o 19-59 years
o Consider in unvaccinated adults >60 years