Diabetes Medications

Family Medicine Residency Noon Conference

November 3, 2017
Ashley Bailey, Pharm.D.
Outline
Prevalence
Type 1 vs Type 2
Non-insulin treatment
Insulin
Future of diabetes treatment

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Why I care about Diabetes
My Husband My Grandma My Dad
(T1 for 22 years) (T2 for >20years) (T2 for 5 years)

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Prevalence
In 2014, 22 million persons living with diabetes
Thats app. 1 in 10 adults in the US
11,000 of these persons live in Delaware Co.
In 2012 the ADA estimated another 8 million
people are living with undiagnosed diabetes.
And that another 86 million people >20y.o.
have prediabetes.
In 2009, there were approximately 11.5 million
ER visits with diabetes listed as one of the
diagnosis.
www.cdc.gov/diabetes/statistics
http://www.diabetes.org/diabetes-basics/statistics/
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Type 1 vs Type 2

Type 1 Type 2
Usually appears in Usually appears in adults
childhood or adolescents Insulin resistance
Impaired Insulin excretion Treatment
Treatment Lifestyle changes
Insulin Oral agents
Injections Insulin
Pumps

http://jaoa.org/article.aspx?articleid=2101921
Cefalu, W. et al. Diabetes Care 2017;40(1):S1S2.
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Non-insulin treatment options
Biguanides
Glucagon-Like Peptide-1 Agonists (GLP-1 RA)
Sodium-glucose Cotransporter-2 inhibitors (SGLT2i)
Dipeptidyl Peptidase-4 inhibitors (DPP4i)
Thiazolidinediones (TZD)
Sulfonylureas (SU)
Meglitinides (GLN)
Others

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Biguanides
Metformin (Glucophage)
MOA
glucose production and absorption and insulin
sensitivity
Warnings/precautions
Lactic Acidosis, Iodinated contrast, Vit B12 Deficiency
Adverse reactions
GI distress
Renal adjustments
CI with sCr >1.5 and >1.4 or GFR <30
Garber, A. Endocr Pract 2016;22(1)
Hong J. Diabetes Care 2013;36: 1304-11
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Glucagon-Like Peptide-1 Agonists
(GLP-1)
Liragluitide (Victoza), Exenatide (Byetta, Bydureon),
Dulaglutide (Trulicity), Albiglutide (Tanzeum),
Lixisenatide (Adlyxin)
MOA
insulin secretion and B-cell growth, glucagon
secretion and food intake
Warnings/Precautions
Risk of thyroid C-cell tumors, pancreatitis
Adverse effects
GI
Garber, A. Endocr Pract 2016;22(1)
Marso S. NEJM 2016;375(4): 311-22.

Renal Adjustments Nauck M Diabetes Care 2013;36(2):S245-252

Nissen, S. NEJM. 2007;356(24): 2457-71

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Sodium-glucose Cotransporter-2
Inhibitors (SGLT2i)
Canagliflozin (Invokana), Dapagliflozin (Farxiga),
Empagliflozin (Jardiance)
MOA
Reduces glucose reabsorption from the proximal renal
tubule
Warnings/Precautions
Euglycemic DKA, Genital mycotic infections, Bone
fractures, Lower limb amputation
Adverse effects
Hyperkalemia, Hypotension, UTI
Fadini GP. Lancet 2017; 5: 680-681.

Renal Adjustments Garber, A. Endocr Pract 2016;22(1)

Taylor S.Lancet 2015;3:8.
Zinman B NEJM. 015;373(22):2117-28
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Dipeptidyl Peptidase-4 Inhibitors
(DPP4i)
Alogliptin (Nesina), Linagliptin (Tradjenta)*,
Saxagliptin (Onglyza) , Sitagliptin (Januvia)
MOA
glucose dependent insulin secretion, glucose
dependent glucagon secretion
Warnings/Precautions
Pancreatitis, HF, arthralgia, hepatotoxicity
Adverse effects
GI, nasopharyngitis
Renal adjustments*
Garber, A. Endocr Pract 2016;22(1)
Green J. NEJM 2015;373(3):232-42.

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Thiazolidinediones (TZD)
Pioglitazone (Actos), Rosiglitazone (Avandia)
MOA
insulin sensitivity
Warnings/Precautions
Black Box: HF exacerbation, fractures, edema, bladder
CA, macular edema
Adverse effects
Weight gain, LDL/HDL/TC, HA, URI
No renal adjustments
Burton, T. Wall Street Journal. www.wsj.com
Garber, A. Endocr Pract 2016;22(1)
Graham D. JAMA 2010;304(4):411-18.
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Sulfonylureas (SU)
Glimepiride (Amaryl), Glipizide (Glucotrol),
Glyburide (Diabeta, Glynase)
MOA
insulin excretion
Warnings/Precautions
Sulfa allergy
Adverse Effects
GI distress(bloating, flatulence), Hypoglycemia, wt. gain
Renal Adjustments
Beers Criteria
Garber, A. Endocr Pract 2016;22(1)
Hong J. Diabetes Care 2013;36: 1304-11.

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Meglitinides (GLN)
Nateglinide (Starlix), Repaglinide (Prandin)
MOA
insulin secretion
Adverse reactions
URI, hypoglycemia, wt gain
Renal Adjustments

Garber, A. Endocr Pract 2016;22(1)

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Other Agents
Alpha-glucosidase Inhibitors
Acarbose (Precose), Miglitol (Glyset)
Slows carb digestion/absorption
0.5-0.8%, GI distress
Antilipemic agent (adjunct therapy)
Colesevelam (Welchol)
Bind bile in intestines, causing hepatic production of bile and
gluconeogenesis
O.5-1%, GI distress, may decrease absorption of other medications
Dopamine agonist
Bromocriptine (Cycloset)
Modulated hypothalamic regulation of metabolism and insulin sensitivity
0.1%, Nausea, dizziness/syncope, fatigue, rhinitis
Amylin analog injection
Pramlinitide (Symlin)
Approved in T1 and T2 to delay gastric emptying and secretion of glucagon
*Insulin dose needs reduced when added as combination
Garber, A. Endocr Pract 2016;22(1
Shivaprasad C, et al. Indian J Endocriol Metab 2011; 15(1): S17-S24.
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Insulin Treatment
Long Acting (Basal)
Degludec (Tresiba), Detemir (Levemir), Glargine (Lantus,
Toujeo*)
Intermediate Acting
NPH (Humulin N)

Short
Regular (Humulin/Novolin R, U-500)

Rapid
Aspart (Novolog), Lispro (Humalog), Glulisine (Apidra)

Mix
Novolog 70/30, Humalog 75/25, Humalog 50/50
Chiang J, et al. Diabetes Care 2016; 2034-51.
Petznick, A. JAOA. 2013;113[7]:507
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Insulin Duration Comparison

https://iuhealthballmemorialhospital.ellucid.com/documents/view/5714

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Future of Diabetes Management
Continuous Glucose Monitors (CGM)
hypoglycemia and HgbA1C
Smart pumps (Artificial Pancreas)
Bi-hormonal pumps
Insulin and glucagon
mean blood glucose, hypoglycemia, ketones

Buckingham B., et al. Lancet 2016;4: 191-3.

Poolsup N. Diabetol Metab Syndrome 2013; 5:39.
Pohl R., et al. J Diabetes Sce Techol 2015;9(1):8-16
Russel S. Lancet 2016;4: 233-243
Tamborlane W. NEJM 2008;359(14): 1464-76
.
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 References
1. Buckingham B., et al. Closed-loop Control in Type 1 Diabetes. Lancet 2016;4: 191-3.
2. Burton, T. FDA Removes marketing Limits on Diabetes Drug Avandia. Wall Street Journal. www.wsj.com
3. Cefalu, W. et al. American Diabetes Association, Standards of Medical care in Diabetes 2017. Diabetes Care 2017;40(1):S1S2.
4. Chiang J, et al. Type 1 Diabetes Through the Life Span: A Position Statement of the American Diabetes Association. Diabetes Care 2016; 2034-51.
5. Fadini GP, et al. SGLT2 inhibitors and amputations in the US FDA Adverse Event Reporting System. Lancet 2017; 5: 680-681.
6. Garber, A. et al. AACE/ACE Consensus Statement. Endocr Pract 2016;22(1)
7. Graham D., et al. Risk of Acute Myocardial Infarction, Stroke, Heart Failure, and Death in Elderly Medicare Patients Treated with Rosiglitazone or Pioglitazone.
JAMA 2010;304(4):411-18.
8. Green J., et al. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. NEJM 2015;373(3):232-42.
9. Hong J., et al. Effects of Metformin Versus Glipizide in Cardiovascular Outcomes in Patient with Type 2 Diabetes and Coronary Artery Disease. Diabetes Care
2013;36: 1304-11.
10. Lexi-Comp, Inc. (Lexi-Drugs). Lexi-Comp, Inc.; October 27, 2016.
11. Marso S., et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. NEJM 2016;375(4): 311-22.
12. Nauck M., et al. Do GLP-1-Based Therapies Increase Cancer Risks. Diabetes Care 2013;36(2):S245-252.
13. Nissen, S., et al. Effect of Rosiglitazone of the Risk of Myocardial Infarction and Death from Cardiovascular Causes. NEJM. 2007;356(24): 2457-71
14. Petznick, A. Identifying and Addressing Barriers to Insulin Acceptance and Adherence in Patients with Type 2 Diabetes Mellitus. The Journal of the American
Osteopathic Association. 2013;113[7]:507
15. Poolsup N., et al. Systematic Review and Meta-analysis of the Effectiveness of Continuous Glucose Monitoring on Glucose Control in Diabetes. Diabetol
Metab Syndrome 2013; 5:39.
16. Pohl R., et al. Development of Stable Liquid Glucagon Formulations for use in Artificial Pancreas. J Diabetes Sce Techol 2015;9(1):8-16
17. Russel S. et al. Day and Night Glycemic control with Bionic Pancreas Versus conventional Insulin Pump Therapy in Preadolescent Children with Type 1
Diabetes: A Randomized Crossover Trial. Lancet 2016;4: 233-243.
18. Shivaprasad C, et al. Bromocriptine in Type 2 Diabetes Mellitus. Indian J Endocriol Metab 2011; 15(1): S17-S24.
19. Tamborlane W., et al. Continuous Glucose Monitoring and Intensive Treatment of Type 1 Diabetes. NEJM 2008;359(14): 1464-76
20. Taylor S., et al. Possible adverse effects of SGLT2 inhibitors on bone. Lancet 2015;3:8.
21. www.cdc.gov/diabetes/statistics
22. www.diabetes.org/diabetes-basics/statistics
23. Zinman B., et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. NEJM 2015;373(22):2117-2

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 QUESTIONS?

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