Diabetes Topic

Discussion
Kristen Parker, PharmD
PGY-1 Pharmacy Resident
 Type 1 vs Type 2

M Donath, et al. Immunology. 2011.

Type 1
 Insulin
• Essential for patients with Type 1 Diabetes
• Initiation
• 50% prandial, 50% basal
• TTD estimated using 0.4-1 units/kg/day

Diabetes Care. 2020;43:S98-110)

Type 2 Diabetes
 Diagnosis

Fasting BG Random
A1C >6.5%
>126 BG >200

Polyuria Polydipsia Polyphagia

Diabetes Care. 2020;43:S98-110

 Treatment goals

A1C Post-
Fasting
prandial
< 7% 80-130
< 180

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A1C conversion
Mean plasma
HbA1C (%)
glucose (mg/dL)
5 97
6 126
7 154
8 183
9 212
10 240
11 269
12 298

Mean BG = (28.7 x A1C) – 46.7

 Glucose monitoring

Self-monitoring of Continuous
blood glucose glucose monitoring
(SMBG) (CGM)
 Type 2 treatment options

Non-pharmacologic Injectable agents Oral agents

• Weight loss • Insulin • Metformin
• Nutrition • GLP-1 receptor • GLP-1 receptor
• Physical activity agonists agonist (Rybelsus®)
• Smoking cessation • DPP-4 inhibitors
• SGLT2 inhibitors
• Sulfonylureas
• Thiazolidinediones

Diabetes Care. 2020;43:S98-110

Diabetes Care. 2020;43:S98-110
 Metformin

• Initiate at the time of

diagnosis unless
contraindicated
• Beneficial effects on:
weight, A1C (↓1-2%),
and cardiovascular
mortality

Diabetes Care. 2020;43:S98-110

 Metformin limitations
• Renal impairments dosing
• CrCl 45-59 mL/min – max dose of 1.5 g/day
• CrCl 30-44 mL/min – initiation of therapy not
recommended, max of 500 mg BID
• CrCl <30 mL/min – avoid use
• Side effect management
• XR formulation may provide benefit
• Instruct patient to take with food
• Use gradual dose titrations

Diabetes Care. 2020;43:S98-110

 When to use specific agents

“Fix fasting first”

A1C A1C
<10% >10%

Agents targeting fasting

glucose
• Long acting basal insulin
• Once-weekly GLP-1 receptor
agonists

Diabetes Care. 2020;43:S98-110

 GLP-1 receptor agonists
• Byetta® or Bydureon® • MOA:
(exenatide) • Increase insulin
secretion
• Trulicity® (dulaglutide)
• Decrease glucagon
• Ozempic® or Rybelsus® secretion
(semaglutide) • Slow gastric emptying
• Victoza® (liraglutide)
• Adlyxin® (lixisenatide)

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 GLP-1 receptor agonists

Drugwatch.com
 GLP-1 receptor agonists
• Boxed warning
• Risk of thyroid carcinomas - avoid use in patients with a
family history of thyroid cancers
• Side effects
• Nausea
• Weight loss
• Warnings
• Pancreatitis
• Avoid use in patients with severe GI disease

Diabetes Care. 2020;43:S98-110

 When to use specific agents

Agents targeting prandial glucose

• Mealtime insulin
• Daily GLP-1 receptor agonists
• DPP-4 inhibitors
• SGLT2 inhibitors

A1C A1C
<10% >10%

Agents targeting fasting glucose

• Long acting basal insulin
• Once-weekly GLP-1 receptor agonists

Diabetes Care. 2020;43:S98-110

 SGLT2 inhibitors

• Jardiance®
(empagliflozin)
• Farxiga® (dapagliflozin)
• Invokana®
(canagliflozin)
• Steglatro®
(ertugliflzoin)

Van Bommel E, et al. CJASN. 2017;12:700-10

 SGLT2 inhibitors
• Boxed Warning
• Increased risk of foot and leg amputations
• Contraindicated in severe renal impairment
(eGFR<30)
• Risk of genital and urinary tract infections

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 DPP4 inhibitors
• Tradjenta® (linagliptin) • MOA:
• Januvia® (sitagliptin) • Increase insulin
secretion
• Onglyza® (saxagliptin) • Decrease glucagon
• Nesina® (alogliptin) secretion
• Monitoring
• Risk of pancreatitis
• Require renal dose
adjustment (except
linagliptin)

Diabetes Care. 2020;43:S98-110

 Sulfonylureas
• Glimepiride • Pros
• Glipizide • Inexpensive

• Glyburide • Cons
• Risk of hypoglycemia
• Avoid in sulfa allergy
• MOA: stimulate insulin • Potential for weight
secretion and decrease gain
postprandial glucose

Diabetes Care. 2020;43:S98-110

 Thiazolidiones
• Pioglitizone
• Rosiglitazone
• MOA: increase
peripheral insulin
sensitivity via PPAR
agonist activity
• Safety:
• Avoid in NYHA Class
III/IV heart failure
• Avoid in patients with
bladder cancer
Diabetes Care. 2020;43:S98-110, Cheng A, et al. Canadian Medical Association Journal. 2005.
 Others

Alpha-glucosidase Bile acid Dopamine-2

Meglitinides Amylin mimetic
inhibitors sequestrants agonist

Acarbose Nateglinide
Colesevelam Bromocriptine Pramlintide
Miglitol Repaglinide

MOA: stimulate
Hypoglycemia Can cause decreased High risk of
insulin secretion and
causes by these absorption of other hypoglycemia if used
decrease
agents cannot be drugs with insulin
postprandial glucose
treated with
sucrose, must be
treated with glucose
specifically
Take before meals

Dose should be
administered with
the first bite of each
May cause weight
meal
gain and
hypoglycemia

Diabetes Care. 2020;43:S98-110

Insulin
 Initiating insulin
• Starting Dose
• Type 1: 0.4-1 units/kg/day
• 50% basal, 50% prandial
• Type 2: 0.1-0.2 units/kg/day
• Start with basal only

Diabetes Care. 2020;43:S98-110

 Insulin-to-carbohydrate ratio

• Rule of 500

# of grams of
carbohydrates
500 TDD covered by 1
units of rapid-
acting insulin

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 Correction factor

• 1800 Rule

1 unit of
insulin will
1800 TDD
correct BG by
this amount

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 Titrating insulin
• General rule
• Increase by 10-20% of TDD
• Consider addition of prandial (bolus) if needed

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 Insulin comparison
Onset Peak Duration
Rapid-acting Lispro 15-30 min 0.5-3 hours <5 hours
(Humalog®)
Aspart 10-20 min 1-3 hours 3-5 hours
(Novolog®)
Glulisine 15-30 min 60-90 min <5 hours
(Apidra®)
Inhaled insulin Immediate 12-15 min 180
(Afreeza®) minutes
Short-acting Regular human 15-30 min 2.5-5 hours 4-12 hours
insulin
(Novolin R®,
Humulin R®)

Adapted from Diabeteshealth.com

 Insulin comparison
Onset Peak Duration
Intermediate NPH 1-2 hours 4-12 hours 14-24 hours
acting (Novolin® N,
Humulin® N)
Long-acting Detemir 3-4 hours None 6-23 hours
(Levemir®)
Glargine 3-4 hours None >24 hours
(Lantus®)
Glargine 6 hours None >24 hours
(Toujeo®)
Degludec 1 hours None >24 hours
(Tresiba®)

Adapted from Diabeteshealth.com

 Insulin comparison

Grey H. Healthline. 2019.

 Package sizes
• Pens • Vials
• Most pens • Most vials
• 3 mL • 10 mL
• Toujeo® (U-300) • Regular insulin
• SoloStar: 1.5 mL • 3 mL or 10 mL
• Max SoloStar: 3 mL • U-500
• 20 mL

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 Insulin conversions
Most insulins Add up TDD Convert 1:1

BID NPH to Add up TDD of NPH

Decrease by 20% and
then convert 1:1 to
Glargine glargine

Glargine to BID Decrease glargine dose

Add up TDD of glargine by 20% and divide in 2
NPH doses

Toujeo® to
Lantus®, Decrease TDD by 20% Convert 1:1
Basaglar®,
Levemir®

If A1C >8: If A1C <8:

Converting to Add up TDD and Add up TDD and
convert 1:1 divided in 3 decrease by 10% then
U-500 doses divide into 3 doses

Pharmacist’s Letter. 2014.

 Practice
• SJ is currently taking 40 units of Lantus® but needs
to switch to NPH due to cost. What would you
recommend as a starting dose of NPH?
• 40 units x 0.8 = 32 units
• 32 units / 2 doses = 16 units BID
Insulin Patient
Education
Insulin injection technique

https://youtu.be/fJPzkzyuMZ8
 Insulin stability

Room Temp
Rapid acting Novolog® Up to 28 days
Humalog®
Admelog®
Apidra®
Afreeza® 10 days
Short acting Humulin® R 31 days
Humulin® R 40 days
U-500
Novolin® R 42 days

Adapted from Diabeteshealth.com

 Insulin stability

Room Temp
Intermediate Humulin® N 14 days
KwikPen
Humulin® N vial 31 days
Novolin® N 42 days
Long acting Levemir® 42 days
Lantus® 28 days
Basaglar®
Tresiba® 56 days
Toujeo®

Adapted from Diabeteshealth.com

Questions
Diabetes Topic
Discussion
Kristen Parker, PharmD
PGY-1 Pharmacy Resident