SPECIAL GLP-1 TEST YOUR KNOWLEDGE ANSWER #615, PART 5
Correct Answer: a
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In addition to improving his glycemic control, a GLP-1 receptor agonist offers other potential benefits for Paul, including potential weight loss, low incidence of hypoglycemia, and global improvement of cardiovascular risk factors with which he presents.
As discussed in the previous question, GLP-1 receptor agonists have been found to not only improve A1c, but also to improve lipid profile. Additionally, studies have found other cardiovascular risk factors to improve with long-term GLP-1 agonist use. In a follow up study of patients who had been on exenatide for 3 years, in addition to the improvements seen in patients' lipid profiles, significant improvements were also seen in both diastolic and systolic blood pressure, with around 3.5 mmHg improvement for both.14
Studies consistently show weight loss with GLP-1 agonists. Longer follow up studies show significant weight loss is quite durable in many patients.16 The aforementioned 3 year follow up found a mean weight loss of 5.3 kg +/- 0.4 kg from baseline.14
This patient also has problems with hypoglycemia. Incretin-based therapy has been found to cause relatively very low rates of hypoglycemia when used as monotherapy or when combined with metformin. It can, however increase rates of hypoglycemia when combined with insulin or a secretagogue. The manufacturers of liraglutide and exenatide recommend practitioners consider lowering the dose of sulfonylureas when adding a GLP-1 agonist.17,18 The rate of hypoglycemia with exenatide alone or with metformin is approximately 5%, but jumps to approximately 35% when combined with a sulfonylurea.16
References
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Rodbard HW, Jellinger PS, Davidson JA, et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract. 2009; 15:540-59.
Buse JB, et al. Efficacy and safety of exenatide once weekly versus liraglutide in subjects with type 2 diabetes (DURATION-6): a randomised, open-label study. EASD 2011; Abstract 75.
Verspohl EJ. Novel therapeutics for type 2 diabetes: Incretin hormone mimetics (glucagon-like peptide-1 receptor agonists) and dipeptidyl peptidase-4 inhibitors. Pharmacology & Therapeutics 2009; 124(1): 113-38.
Klonoff DC, Buse JB, Nielsen LL, et al. Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin 2008;24:275–286.
Hansen KB, Vilsboll T, Knop FK. Incretin mimetics: a novel therapeutic option for patients with type 2 diabetes – a review. Diabetes Metab Syndr Obes 2010; 3: 155-63.
IDF Clinical Guidelines Task Force. Global guideline for Type 2 diabetes. Brussels: International Diabetes Federation, 2005.
Management of Diabetes Mellitus Update Working Group. (2010). VA/DoD Clinical Practice Guideline for the Management of Diabetes Mellitus. Version 4.0. Washington, DC: Veterans Health Administration and Department of Defense.
Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000; 321: 405-12.
The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Study Group: Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008; 358: 2545-59.
The Action in Diabetes and Vascular Disease Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) Collaborative Group: Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008; 358: 2560-72.
Fonseca VA, Rosenstock J, Wang AC, et al. Colesevelam HCl Improves Glycemic Control and Reduces LDL Cholesterol in Patients with Inadequately Controlled Type 2 Diabetes on Sulfonylurea-Based Therapy. Diabetes Care 2008; 31(8): 1479-84.
Blonde L, Klein EJ, Han J, et al. Interim analysis of the effects of exenatide treatment on A1c, weight, and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes. Diabetes Obes Metab. 2006; 8: 436-47.
Klonoff DC, Buse JB, Nielsen LL, et al. Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin 2008; 24(1): 275-86.
Buse JB, Klonoff DC, Nielsen LL, et al. Metabolic effects of two years of exenatide treatment on diabetes, obesity, and hepatic biomarkers in patients with type 2 diabetes: an interim analysis of datat from the open-label, uncontrolled extension of three double-blind, placebo-controlled trials. Clin Ther. 2007; 29:139-53.
R. Keith, C. Clarifying the Role of Incretin-Based Therapies in the Treatment of Type 2 Diabetes Mellitus. Clinical Therapeutics 2011; 33(5): 511-527.
Victoza [package insert]. Princeton, NJ: Novo Nordisk; 2011.
Byetta [package insert]. San Diego, CA: Amylin Pharmaceuticals; 2011.
Garg R, Chen W, Pendergrass M. Acute pancreatitis in type 2 diabetes treated with exenatide or sitagliptin: a retrospective observational pharmacy claims anaylsis. Diabetes Care 2010;
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