Exenatide QW: a New Treatment Option for Type 2 Diabetes Offering Ease of Use, Improved Efficacy, and Reduced Side Effects

FEATURE ARTICLE Commentary: Exenatide QW: A New Treatment Option for Type 2 Diabetes Offering Ease of Use, Improved Efficacy, and Reduced Side Effects Charles F. Shaefer, Jr., MD Editor’s note: Once-weekly exenatide, (also called incretin mimetics) cur- with GLP-1 receptor agonists is the which has recently been approved for rently in use.3,4 only form of anti-diabetes therapy patients with type 2 diabetes, has great Validation of the acceptance offering proven weight loss. Finally, potential as a new diabetes therapy in clinical practice of GLP-1 GLP-1 receptor agonist therapy is in the primary care setting. This receptor agonists can be found in one of the recommended treatment commentary and the feature article that the recently released American strategies offering a low incidence of follows it (p. 95) offer an overview of Diabetes Association (ADA)/ hypoglycemia, an important aspect this new therapeutic tool and important European Association for the Study of diabetes therapy learned from the insights about its clinical utility. In the of Diabetes (EASD) position state- Action to Control Cardiovascular interest of transparency, however, we ment on the management of type 2 Risk in Diabetes trial.6 want to point out that the authors of diabetes, which placed these drugs As clinicians consider what to do both articles are affiliated with Amylin alongside older, well-accepted agents when metformin and lifestyle change Pharmaceuticals, which manufactures such as sulfonylureas (SUs) and do not adequately control a patient’s exenatide QW and markets it under the thiozolidinediones (TZDs) as a sec- A1C, they frequently ask, “incretin 5 trade name Bydureon. ond-line therapy after metformin. or insulin next?” Fortunately, there GLP-1 receptor agonists are is abundant evidence to inform xenatide once weekly (QW) has described as having high efficacy this decision. Heine et al.7 have recently been introduced for and a low risk of hypoglycemia and shown exenatide twice daily to be weekly subcutaneous injec- E as being on a cost tier (high) equal to non-inferior to insulin glargine for tion as an adjunct to diet and lifestyle other add-on agents except for SUs A1C reduction in a study popula- change for the treatment of type 2 5 (low) and insulin (variable). GLP-1 tion with an average A1C of 8.2%. diabetes. It is the first weekly diabetes receptor agonists are the only class Exenatide QW has been shown to therapy to come to market and offers mentioned with which weight loss is produce lower A1C values than a number of interesting possibilities expected.5 Although gastrointestinal insulin glargine over the course of for clinicians and patients. (GI) issues were cited as side effects an 84-week study, with accompany- Although this treatment is, at its with this class, exenatide QW has a ing significant and durable weight core, the exenatide molecule that has lower incidence of these side effects loss in the exenatide QW group.8 been known for more than a decade than other available GLP-1 receptor Therefore, clinicians can confidently and has been in widespread clinical agonists.3,4 use for at least 7 years,1 exenatide select add-on therapy to metformin QW has a unique microsphere Clinical Properties and lifestyle change, where neces- encapsulation.2 This feature delays For clinicians providing diabetes sary, based on patient-centered absorption, thus producing continu- care, and especially for primary care issues such as the need for lower ous steady-state levels of exenatide providers, these facts have significant hypoglycemia risk, weight reduction, in the bloodstream, which leads to implications. First, there is now clear, and convenience of administra- lower A1C levels and greater weight widely accepted validation for using tion without being concerned about loss than exenatide’s twice-daily for- GLP-1 receptor agonists as an add-on sacrificing efficacy. The new ADA/ mulation3 and a lower incidence of therapy to metformin and lifestyle EASD guidelines clearly favor such side effects than other glucagon-like modification if A1C levels are not patient-centric approaches to peptide-1 (GLP-1) receptor agonists controlled to goal. Second, treatment diabetes management.5 92 Volume 30 Number 3, 2012• CLINICAL DIABETES FEATURE ARTICLE As of this writing, exenatide QW Use in Primary Care and weight reduction afforded by has been available for about 6 weeks. My experience suggests that exena- exenatide QW. Many patients seem It has already found widespread use tide QW use in a busy primary care relieved that the new therapy is not in my practice and has been met practice is likely to fall into one of five insulin. I appreciate that exenatide with almost uniform patient accep- categories. First are patients whose QW is easier and faster to implement tance. Patients seem reassured that diabetes is not well controlled with in the office than other GLP-1 recep- the drug being used (the exenatide metformin and lifestyle therapy who tor agonists or insulin. A single dose molecule) has been in testing and either need to achieve A1C reductions strength, no ramp-up titration, and clinical use for about a decade. All beyond that expected by adding oral no need for self-monitored glucose of the precautions and safety issues agents or need continuing weight determinations make exenatide QW pertaining to exenatide also apply to loss or both. Second are those who simple to implement in the setting of exenatide QW.9 have not tolerated the GI side effects a routine office visit. Exenatide QW and liraglutide, of previous GLP-1 receptor agonists Since the advent of exenatide QW, long-acting GLP-1 receptor agonists, but who are more likely to tolerate a number of previously professed carry box warnings concerning exenatide QW with its less intense side “faithful” GLP-1 receptor agonist medullary thyroid carcinoma in effect profile. A third group includes patients have admitted how often rodents.9,10 The implications of these patients who have not done well (poor they missed their medication either findings in humans are not known, A1C reduction, little weight loss) with because they forgot or because of although it is somewhat reassuring either exenatide twice daily or lira- travel, dining out, or other circum- that there has been no adverse sig- glutide once daily therapy, possibly stances. These patients have done naling for thyroid cancer risk so far because of unreported compliance exceedingly well with once weekly with the clinical use of liraglutide. issues, who may be candidates for dosing at a time convenient for them. more convenient weekly therapy. However, this issue should be dis- Some who have quit exenatide Fourth are patients with literacy, twice daily or liraglutide once daily cussed with patients before they start numeracy, or psychosocial issues because of GI side effects have been using a long-acting GLP-1 receptor who have limited compliance to other willing to consider trying again with agonist. therapies but may be good candidates exenatide QW, with its lesser levels Also, there have been reports for weekly therapy administered in of such side effects. To date, most of small subcutaneous bumps after the clinician’s office. And finally, a have successfully tolerated exena- exenatide QW injection, presumably fifth group includes the few patients tide QW, and none have stopped the a form of foreign-body reaction to who wish to abandon their currently drug because of side effects. So far the microsphere.2 This is a normal effective GLP-1 receptor agonist in my practice, this group constitutes and temporary response, resolving therapy in favor of the more conve- ~ 30% of the exenatide QW users. in ~ 4–6 weeks after any injection. nient weekly dosing of exenatide QW. Perhaps the most rewarding So far, this has been very uncommon Surprisingly, few successful group of patients benefitting from in my exenatide QW patients. exenatide twice daily or liraglutide exenatide QW in our practice has Patients should be reminded once daily patients in my practice been individuals with literacy, that the full effect of treatment is have been motivated to switch numeracy, or psychosocial issues not likely to occur until exenatide to exenatide QW. It seems these that have precluded compliant use of QW has been used for 2 months patients are comfortable with their oral or other injectable agents. These and a steady-state level of exenatide regimen and find little benefit in patients, after learning that there is a has been achieved. In the world of changing. I have realized that those weekly injection that can be given in instant gratification, neither clini- who would like a change to simplify the office, have been more forthcom- cians nor patients should forget to dosing or relieve side effects likely ing about the issues impairing their appreciate this gradual onset of have already done so by quietly opt- use of diabetes treatments and have action. Proactive discussion of all ing for poor compliance. been delighted to come to our office the aspects of exenatide QW use will After initiating lifestyle modi- weekly for their injection of exena- help patients and clinicians employ fication and metformin therapy, a tide QW, a schedule that they and this therapy successfully. Remember: number of patients continue to have our office staff can easily accom- SATISFACTION = RESULTS – A1C levels > 8% and issues with plish. Many of these individuals EXPECTATIONS (T.W. Olsen, excess weight. These patients are previously had no effective control of unpublished observations). likely to benefit from the robust A1C their diabetes and no accountability CLINICAL DIABETES • Volume 30, Number 3, 2012 93 FEATURE ARTICLE partners to help them. Our Thursday combination of clinicians’ expertise DR: Management of hyperglycemia in type 5 2 diabetes: a patient-centered approach.

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