What’s New in Diabetes

Therapy:
The Good News for Your
Patients

LCDR Alexis Epperly

March 2007
 Goals
 Review New FDA Approved
Medications
 Review New Insulin preparations
 Prevention of Type 2 Diabetes
 Glucose Monitor advances
 Review Type 1 Diabetes advances
 What’s on the horizon
 Incretins
 GI tract secretes glucoregulatory hormones
 Glucagon-Like Peptide 1 (GLP-1)
• Secreted by L cells of the ileum
• Inhibits gastric emptying and glucagon
secretion
• Stimulates insulin secretion
• T1/2: 2 minutes
• GLP-1 injection causes beta cell hypertrophy in
rats
 Glucose-dependent Insulinotropic Peptide (GIP)
• Stimulates pancreas to secrete amylin
Reddy,S. Endocrinology update 2006. Clev Clin J Med,2006.
 Exenatide (Byetta)
 Analogue of GLP-1, FDA approved in 2005
 Mechanism: promotes glucose-dependent insulin
secretion
 Indications: Adjunctive therapy of Type 2 DM,
when patients have failed first line oral therapy
 Dose: 5-10 mcg SQ BID < 60 minutes prior to
breakfast and dinner
 Adverse effects: nausea (44%), diarrhea (13%),
hypoglycemia (4-27%, alone and with
metformin/sulfonylurea)
 Secondary benefit: weight loss
 Cost: $183-215/month
http://uuhsc.utah.edu/pharmacy/bulletins/exenatide.html
 Amylin
 Stored in beta cells
 Co-secreted with insulin.
 Decreases gastric emptying, suppresses
glucagon secretion/glucose production,
promotes satiety, and decreases appetite.
 Decreased levels in all diabetics
• Type I lowest levels, no response to
meals

Reddy,S. Endocrinology update 2006. Clev Clin J Med,2006.

 Pramlintide (Symlin)
 Analogue of amylin, FDA approved in 2005
 Mechanism: slows gastric emptying, suppresses
glucagon secretion, increases satiety
 Indication: adjunct to mealtime insulin when
optimal insulin therapy fails to produce adequate
glucose control
 Dose:
• Type 1 DM 15-60 mcg SC AC
• Type 2 DM 60-120 mcg SC AC
 Adverse effects: nausea (30%), HA, fatigue, risk
of insulin-induced hypoglycemia, weight loss
 Cost: $99 -357/month

http://uuhsc.utah.edu/pharmacy/bulletins/pramlintide.html
 Sitagliptin phosphate (Januvia)
 DPP-4 inhibitor, FDA approved Oct 2006
 Mechanism: prolongs activity of incretins
 Indication: Adjunct to diet and exercise in
Type 2 DM alone or in combination with
metformin or TZD
 Dose: 100 mg daily
 Adverse effects: URI, sore throat, diarrhea
 Cost: $175/month

http://uuhsc.utah.edu/pharmacy/bulletins/html
 New Insulin Preparations
Inhaled insulin
 Physiology:

• Alveolar surface area and vascularity

enhance absorption
• Time of onset comparable to fast-acting
SC insulin
• Bioavailability 10% that of SC insulin

Reddy,S. Endocrinology update 2006. Clev Clin J Med,2006.

 Inhaled Insulin (Exubera)
 Dry-powder oral inhalation, FDA approved Jan
2006
 Mechanism: absorbed via pulmonary vasculature.
Rapid onset of action, comparable to short-acting
insulin. Bioavailability only 10% compared to SC
insulin.
 Indications: Type I or Type II DM for pre-meal
dosing
 Dose: Initial pre-meal dose 0.05 mg/kg, adjust
as needed.
• 3 mg inhaled insulin comparable to 9 units SC
 Adverse effects: mild cough (most common); PFT
decline (need PFT’s pre-Rx); hypoglycemia
 Cost: $120 per month
 Detemir (Levimir)
 Insulin analogue, rDNA, FDA approved 2005
 Mechanism: long acting insulin, released more
slowly than human insulin with stable AUC
 Indication: Type 1 DM adult and pediatrics, Type
2 DM adult requiring long acting insulin
 Dose: 10 units daily, titrate as required
 Adverse effects: hypoglycemia, possible bid
dosing due to shorter T1/2 than insulin glargine
 Cost: $30/3ml, $77/10ml
 ADA 2007 Guidelines for Stepwise
Treatment of Type 2 DM
Goal: HgbA1C < 7
 First line: diet, exercise, metformin
 Add: sulfonylurea, TZD, or basal
insulin
 Add: another agent from above list
• Or intensify insulin
 Add or intensify insulin
 Final: intensive insulin + metformin
+/- TZD
American Diabetes Association. Standards of Medical Care in Diabetes—
2007. Diabetes Care. 2007.
 Potential Roles for New Meds in
Stepwise Treatment of Type 2 DM
 First line: diet, exercise, metformin
• Sitagliptin could be used as first-line med
 Add: sulfonylurea, TZD, or basal insulin
• Exenatide could be added here
 Add: another agent from above list
• Or intensify insulin
• Exenatide could be added here
• Pramlintide can be added to mealtime insulin
 Add or intensify insulin
• Pramlintide can be added to mealtime insulin
 Final: intensive insulin + metformin +/- TZD
 Prevention of Type 2 Diabetes
 Diabetes Prevention Program Research
Group 2002 Study
• Pre-diabetics randomized to 3 groups:
 Lifestyle intervention - 58% reduction DM incidence
 Metformin plus standard education – 31% reduction
 Placebo
 Other studies (China, Finland) found
similar results
 Possible protective effects of ramipril,
pravastatin
DPPRG. Reduction in the Incidence of Type 2 Diabetes with
Lifestyle Intervention or Metformin. NEJM.2002
Reddy,S. Endocrinology update 2006. Clev Clin J Med,2006.
 Advances in Glucose Monitors
 GlucoWatch G2 Biographer
• Gives glucose reading every 10 min
• Noninvasive
• Poor correlation when BG low
• Does not replace finger stick monitoring
 Cardiocheck
• Glucose, total cholesterol, ketone,
triglyceride, HDL within 60 seconds each
 Type 1 Diabetes
 Pancreas Transplants
• Islet cell transplants
 90% require insulin after 5 years
 Early research suggests exenatide may delay insulin
requirement
• Partial Pancreas transplants
 Preferred when receiving kidney from relative
 Protects kidney from damage
• Full Pancreas transplants
 Limited by effects of immunosuppressive medications
 50% rejected
 Indicated for Type 1 DM requiring kidney transplant
Al Ghofaili, K. Effect of Exenatide on B Cell Function After Islet Transplantation in Type 1
Diabetes. Transplantation,2007
www.diabetes.org1/25/2007
 The Horizon
 GLP-1 analogues resistant to proteases
 Oral insulin (Emisphere,Inc.) being
studied – results look promising
 Role of Vitamin D deficiency or
insufficiency in development of Type I
DM
 Gene therapy
 Acknowledgements

 Dr Senkei Yoshida, USNH Okinawa,

Japanese National Internship Program,
2006-2007