GLP-1 Agonist
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This document summarizes information about GLP-1 receptor agonists for treating diabetes. It reviews the pharmacology and mechanism of action of GLP-1 receptor agonists, comparing the advantages and disadvantages of the class. Specific products are discussed, including dosing and side effects. Head-to-head clinical trials comparing different GLP-1 receptor agonists are summarized. Safety issues like the black box warning for thyroid cancer risk are also addressed. The document provides an overview of GLP-1 receptor agonists for non-insulin treatment of diabetes.
![Works Cited/Resources
Trujillo JM, Nuffer W, Ellis SL. GLP-1 receptor agonists: a review of head-to-head clinical studies. Therapeutic
Advances in Endocrinology and Metabolism. 2015;6(1):19-28.
Trulicity. In: Lexi-drugs Online. Hudson (OH): Lexi-Comp, Inc.;[updated 02/11/16; accessed 03/03/16].
http://online.lexi.com.ezproxymcp.flo.org/lco/action/doc/retrieve/docid/patch_f/5355165#rfs
Tanzeum. In: Lexi-drugs Online. Hudson (OH): Lexi-Comp, Inc.;[updated 02/04/16; accessed 03/03/16].
http://online.lexi.com.ezproxymcp.flo.org/lco/action/doc/retrieve/docid/patch_f/5100162
Byetta. In: Lexi-drugs Online. Hudson (OH): Lexi-Comp, Inc.;[updated 02/15/16; accessed 03/03/16].
http://online.lexi.com.ezproxymcp.flo.org/lco/action/doc/retrieve/docid/patch_f/50062
Victoza. In: Lexi-drugs Online. Hudson (OH): Lexi-Comp, Inc.;[updated 02/15/16; accessed 03/03/16].
http://online.lexi.com.ezproxymcp.flo.org/lco/action/doc/retrieve/docid/patch_f/2144379
FDA MedWatch. http://www.fda.gov/Safety/MedWatch/
VA Pharmacy Benefits Management Services. VA National Formulary. Accessed 03/03/16
http://www.pbm.va.gov/nationalformulary.asp](https://image.slidesharecdn.com/8da197b4-ff30-45f7-a8d3-7a534a0d3962-160518002942/85/GLP-1-Agonist-18-320.jpg)
GLP-1 Agonist
- 1. Non-insulin Injectable Antidiabetics GLP-1 Receptor Agonists Linh Huynh MCPHS University, PharmD 2016 Candidate APPE Institutional Rotation - VA West Roxbury Preceptor: Dr. Susan Jacobson Date: 03/04/2016
- 2. Objectives Review the pharmacology of GLP-1 Receptor Agonists Highlight the advantages and disadvantages of GLP-1 RA Compare the products of this class based on a review of clinical trials Discuss the safety and warning issues of GLP-1 RAs
- 4. Non-insulin Injectable Antidiabetics - An Overview Glucagon-like, peptide-1 (GLP-1) agonist or incretin mimetic (INJECTION) - 1% to 1.5% reduction in A1C MOA: Stimulation of GLP-1 receptors results in increased insulin secretion in response to elevated blood glucose, decreased glucagon secretion, slowed gastric emptying, and increased satiety. (GLP-1 is an incretin hormone.) Generic (Brand) Dose Advantages Disadvantages Albiglutide (Tanzeum) - need to be reconstituted Dulaglutide (Trulicity) Exenatide (Byetta) Exenatide extended-release (Bydureon) Liraglutide (Victoza) Albiglutide INTIAL 30 mg SC once weekly Dulaglutide INITIAL 0.75 mg SC once weekly Exenatide INITIAL: 5 mcg SC BID Exenatide extended-release INITIAL: 2 mg SC once weekly Liraglutide INITIAL: 0.6 mg SC once daily x 1 week, then increase to 1.2 mg SC once daily - Lack of hypoglycemia when used as monotherapy - Weight loss - Reduces postprandial glucose values - In patients who need more than one or two antidiabetes agents, combination injectable therapies of basal insulin and a GLP-1 agonist is an efficient, emerging strategy. - Headache - Nausea (often transient) - Diarrhea - Use with caution in renal dysfunction - Avoid in severe renal impairment (exenatide) - May be associated with pancreatitis - Associated with thyroid cell cancer in rodents (check family Hx) - May be associated with renal insufficiency
- 5. What do you think?... Would there be hypoglycemic episode when GLP-1 RA is co-administered with: Insulin ? Metformin ? Glipizide ?
- 6. What do you think?... Would concomitant use of a DDP-4 inhibitor enhance the effect(s) of GLP-1 RA?
- 8. Comparisons of Products GLP-1 receptor agonists: a review of head to- head clinical studies Trujillo JM, Nuffer W, Ellis SL. GLP-1 receptor agonists: a review of head-to-head clinical studies. Therapeutic Advances in Endocrinology and Metabolism. 2015;6(1):19-28.
- 9. Trujillo JM, Nuffer W, Ellis SL. GLP-1 receptor agonists: a review of head-to-head clinical studies. Therapeutic Advances in Endocrinology and Metabolism. 2015;6(1):19-28.
- 10. Trujillo JM, Nuffer W, Ellis SL. GLP-1 receptor agonists: a review of head-to-head clinical studies. Therapeutic Advances in Endocrinology and Metabolism. 2015;6(1):19-28.
- 11. Trujillo JM, Nuffer W, Ellis SL. GLP-1 receptor agonists: a review of head-to-head clinical studies. Therapeutic Advances in Endocrinology and Metabolism. 2015;6(1):19-28.
- 12. Trujillo JM, Nuffer W, Ellis SL. GLP-1 receptor agonists: a review of head-to-head clinical studies. Therapeutic Advances in Endocrinology and Metabolism. 2015;6(1):19-28.
- 13. SUMMARY OF THE STUDIES STUDIES COMPARATORS A1C CHANGES WEIGHT CHANGES NAUSEA/VOMI TING DIARRHEA INJECTION- SITE RXN LEAD-6 Byetta Victoza Byetta < Victoza Similar reduction Byetta > Victoza Byetta < Victoza Byetta > Victoza DURATION-6 Bydureon Victoza Bydureon < Victoza Bydureon < Victoza (reduction) Bydureon < Victoza Bydureon < Victoza Bydureon > Victoza HARMONY-7 Tanzeum Victoza Tanzeum non- inferior to Victoza Tanzeum < Victoza (reduction) Tanzeum < Victoza Tanzeum > Victoza Tanzeum > Victoza AWARD-1 Trulicity 1.5mg Trulicity 0.75mg Byetta Placebo Trulicity both doses > Byetta > placebo Trulicity 1.5 > Byetta: not significant Trulicity 0.75 < Byetta: significant Trulicity 1.5 > Byetta > Trulicity 0.75 Trulicity 1.5 > Trulicity 0.75 > Byetta Trulicity 1.5 = Byetta > Trulicity 0.75 AWARD-6 Trulicity 1.5 Victoza Trulicity non- inferior to Victora Trulicity < Victoza (reduction) Trulicity > Victoza (nausea), < (vomiting) Trulicity = Victoza Trulicity < Victoza
- 14. SAFETY ISSUES and WARNINGS of GLP-1 RA Black Box Warning: Boxed warning for Risk of Thyroid T-cell Tumor (dose- related and duration-dependent) Contraindication: Contraindicated in patients with personal or family history of medullary thyroid carcinoma and in patients with Multiple Endocrine Neoplasia Type 2 REMS To increase awareness of risk for acute pancreatitis and potential risk of medullary thyroid carcinoma
- 15. ANTIDIABETIC DRUGS - A SUMMARY CLASS DRUGS A1C REDUCTION EFFECTS ON WEIGHT HYPOGLYCEMIC CONSIDERATION Alpha- glucosidase inhibitor Acarbose (Precose, others) Miglitol (Glyset) 0.5 - 1% Weight neutral Lack of hypoglycemia when used as monotherapy Amylin analog Pramlintide (Symlin) 0.5 - 1% Weight loss Lack of hypoglycemia when used as monotherapy Biguanide Metformin (Glucophage, Glucophage XR) *Available in combination with other classes 1 - 1.5% Weight neutral Lack of hypoglycemia when used as monotherapy DPP-4 Inhibitor Alogliptin (Nesina) With metformin (Kazano), pioglitazone (Oseni) Linagliptin (Tradjenta) With metformin (Jentadueto), empagliflozin (Glyxambi) Saxagliptin (Onglyza) With metformin (Kombiglyze XR) Sitagliptin (Januvia) With metformin (Janumet, Janumet XR), simvastatin (Juvisync) 0.5 - 1% Weight neutral Lack of hypoglycemia when used as monotherapy GLP-1 Agonist (INJECTION) Albiglutide (Tanzeum) - need to be reconstituted Dulaglutide (Trulicity) Exenatide (Byetta); Exenatide extended-release (Bydureon) Liraglutide (Victoza) 1 - 1.5% Weight loss Lack of hypoglycemia when used as monotherapy Meglitinide Nateglinide (Starlix) Repaglinide (Prandin, others); With metformin (PrandiMet) 0.5 - 1% Weight gain Hypoglycemia if taken without foods or severe renal impairment
- 16. ANTIDIABETIC DRUGS - A SUMMARY (continued) CLASS DRUGS A1C REDUCTION EFFECTS ON WEIGHT HYPOGLYCEMIC CONSIDERATION SGLT-2 Inhibitor Canagliflozin (Invokana), With metformin (Invokamet) Dapagliflozin (Farxiga) Empagliflozin (Jardiance), With linagliptin (Glyxambi) 0.5 - 1% Weight loss Lack of hypoglycemia when used as monotherapy Sulfonylurea1st generation Chlorpropamide (Diabinese, others) Tolazamide (Tolinase, others) Tolbutamide (Orinase, others) 1 - 1.5% Weight gain Hypoglycemia more common compared with second-generation sulfonylureas Sulfonylurea-2nd generation Glyburide (Diabeta, Glynase, Micronase, others) With metformin (Glucovance) Glipizide (Glucotrol, Glucotrol XL, others) With metformin (Metaglip) Glimepiride (Amaryl, others) With metformin (Amaryl M), pioglitazone (Duetact), rosiglitazone (Avandaryl) 1 - 1.5% Weight gain (glyburide more than glipizide, glimepiride) Hypoglycemia, especially with renal dysfunction (less with glimepiride versus glyburide) Thiazolidinedione (TZD) Pioglitazone (Actos) With metformin (Actoplus Met or Actoplus Met XR), glimepiride (Duetact), alogliptin (Oseni) Rosiglitazone (Avandia) With metformin (Avandamet), glimepiride (Avandaryl) 1 - 1.5% Weight gain Lack of hypoglycemia when used as monotherapy Bile acid sequestrant Colesevelam (Welchol) 0.5 - 1% Weight neutral Lack of hypoglycemia when used as monotherapy
- 17. VA National Formulary (Dec 2015) for Glycemic Control 1.Insulin Aspart 2.Insulin Aspart Protamine/Insulin Aspart (70/30) 3.Insulin Human (NPH/REG) (50/50) 4.Insulin Human (NPH/REG) (70/30) 5.Insulin Human NPH 100U/mL 6.Insulin Human Regular 100U/mL 7.Insulin Long Acting Analog 8.Acarbose 9.Glipizide 10.Metformin 11.Saxagliptin
- 18. Works Cited/Resources Trujillo JM, Nuffer W, Ellis SL. GLP-1 receptor agonists: a review of head-to-head clinical studies. Therapeutic Advances in Endocrinology and Metabolism. 2015;6(1):19-28. Trulicity. In: Lexi-drugs Online. Hudson (OH): Lexi-Comp, Inc.;[updated 02/11/16; accessed 03/03/16]. http://online.lexi.com.ezproxymcp.flo.org/lco/action/doc/retrieve/docid/patch_f/5355165#rfs Tanzeum. In: Lexi-drugs Online. Hudson (OH): Lexi-Comp, Inc.;[updated 02/04/16; accessed 03/03/16]. http://online.lexi.com.ezproxymcp.flo.org/lco/action/doc/retrieve/docid/patch_f/5100162 Byetta. In: Lexi-drugs Online. Hudson (OH): Lexi-Comp, Inc.;[updated 02/15/16; accessed 03/03/16]. http://online.lexi.com.ezproxymcp.flo.org/lco/action/doc/retrieve/docid/patch_f/50062 Victoza. In: Lexi-drugs Online. Hudson (OH): Lexi-Comp, Inc.;[updated 02/15/16; accessed 03/03/16]. http://online.lexi.com.ezproxymcp.flo.org/lco/action/doc/retrieve/docid/patch_f/2144379 FDA MedWatch. http://www.fda.gov/Safety/MedWatch/ VA Pharmacy Benefits Management Services. VA National Formulary. Accessed 03/03/16 http://www.pbm.va.gov/nationalformulary.asp
- 19. Continuous subcutaneous exenatide delivery Phase III trials Once or twice yearly administration !!! ITCA 650 (Intarcia Therapeutic, Inc)