Download Insulin delivery options

Type 2 diabetes treatment:
Old and New
Emily Szmuilowicz, MD, MS
Assistant Professor of Medicine
Division of Endocrinology
Northwestern University
Factors in deciding between therapies
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Treatment goals (and how far from goal)
Costs
Adverse effects, especially hypoglycemia.
Need for flexibility, eating patterns
Patterns of blood glucose before/after eating
Patient characteristics
Diabetes treatment
GLYCEMIC GOALS
Treatment goals
American Diabetes Association. Standards of Medical Care in Diabetes  2015. Diabetes
Care 2015; 38 (S1)
Relationship between
“A1c” and blood glucose
Nathan D et al., for the A1c-Derived Average Glucose (ADAG) Study Group. Diabetes Care
2008
Diabetes treatment
TREATMENT OPTIONS
Lifestyle modifications
• Increasing physical activity
• Nutrition therapy
• Weight loss
Treatment options
diabetesmanager.pbworks.com. Accessed 9-2015.
Medications:
Metformin
How it
works
Advantages
Disadvantages
Cost
• ↓ liver
glucose
production
• Helps body
use insulin
better
• Extensive clinical
experience
• Rare hypoglycemia
• Likely CVD events
(UKPDS)
• Weight
neutral/loss
• GI side effects
• Lactic acidosis risk
(rare)
• Vitamin B12
deficiency
• Multiple
contraindications:
CKD, acidosis,
hypoxia,
dehydration, etc.
Low
A1c ↓
1.0–2.0%
Medications:
Sulfonylureas (glipizide, glimepiride)
How they
work
Advantages
 Insulin
release from
pancreas
• Extensive
experience
•  microvascular
complication
(UKPDS)
A1c ↓
1.0–2.0%
Disadvantages
• Hypoglycemia
• Weight gain
Cost
Low
Medications:
Meglitinides (repaglinide, nateglinide)
Mechanism/
Action
 Insulin
release from
pancreas
Advantages
•  glucose after
eating
• Flexibility
• Short duration of
action
A1c ↓
0.5-1.5%*
*repaglinide more effective than nateglinide
Disadvantages
• Hypoglycemia
• Weight gain
• Multiple daily
doses
Cost
High
Medications:
Incretin mimetics
DPP-4 inhibitors
x
GLP-1 analogs
+
Ahren B. Nature Reviews Drug Discovery 2009; 8: 369.
Medications: GLP-1 analogs
(exenatide, liraglutide, dulaglutide)
How they
work
•  insulin
•  glucagon
• slows gastric
emptying
• satiety
A1c ↓
0.5-1.5%
Advantages
Disadvantages
Cost
• No hypoglycemia • GI side effects
High
• Weight loss
(nausea/vomiting)
• ? Cardiovascular • Injection
protective actions • Unknown long-term
safety
• ?pancreatitis
• thyroid c-cell tumors
in rodents
Medications: DPP-4 inhibitors
(sitagliptin, linagliptin, saxagliptin)
Mechanism/
Action
•  insulin
•  glucagon
A1c ↓
0.5 - 0.8%
Advantages
Disadvantages
• No hypoglycemia • modest efficacy
• Well tolerated
• ?pancreatitis
• Severe joint pain
• ?  risk of heart
failure (saxagliptin)
• Unknown longterm safety
Cost
High
Medications:
Thiazolidinediones (pioglitazone,rosiglitazone)
How they
work
Advantages
• Helps body use
insulin better
( insulin
sensitivity)
• no hypoglycemia
• durability
• improves HDL
• ? ↓ heart attack
(pioglit.)
A1c ↓
0.5–1.4%
Disadvantages
• weight gain
• fluid retention/
heart failure
• bone fractures
•  LDL (rosiglit.)
• ? ↑ heart attack
(rosiglit.)
• ? ↑ bladder
cancer (pioglit.)
Cost
High
Medications: SGLT2 inhibitors
(canagliflozin, empagliflozin, dapagliflozin, etc)
How they
work
Advantages
•  glucose
excretion by
kidneys
•  blood
glucose
•  weight
•  BP
• Low risk of
hypoglycemia
A1c ↓
0.5 –0.7 %
Disadvantages
Cost
•  genital mycotic
infections, urinary
tract infections
• ? long-term safety of
chronic glucosuria
• hypotension
• “Euglycemic DKA”
•  fractures /
↓bone density
• hypotension
High
Medications:
Insulin
• Insulin therapy frequently required due to
progressive loss of pancreas (“beta-cell”) function
• Initial therapy if:
–  glucose (e.g., >300 mg/dL) or HbA1c (e.g. >10%)
– Significant hyperglycemic symptoms
– Necessary when catabolic symptoms or ketonuria
(reflects profound insulin deficiency)
• If no evidence of T1DM, may be possible to taper
insulin partially or entirely after symptoms
relieved and glucotoxicity resolved
Medications:
Insulin
Mechanism/A
ction
Advantages
• ↓ glucose
• Universally
release by the effective
liver
• No dose limit
• moves glucose • ↓ microvascular
from blood
disease
into muscle/fat • improved
A1c ↓
cholesterol
1.0 – 3.5%
Disadvantages
• Hypoglycemia
• Weight gain
• Injection (1 – 4+)
• Training
requirements
• “Stigma” (for
patients)
Cost

Physiologic insulin delivery
DeWitt DE et al. JAMA 2003; 289: 2254.
Insulin delivery options
http://diabetes.niddk.nih.gov/dm/pubs/insulin/
Insulin delivery options
http://diabetes.niddk.nih.gov/dm/pubs/insulin/
Insulin delivery options
http://diabetes.niddk.nih.gov/dm/pubs/insulin/
Diabetes treatment
PUTTING IT ALL TOGETHER
Treatment of T2DM
American Diabetes Association. Standards of Medical Care in Diabetes  2015. Diabetes
Care 2015; 38 (S1)