Table of Contents
Pathophysiology of type 2 diabetes mellitus: potential role of incretin-based therapies
Glucose-lowering effects of incretin-based therapies
Safety, tolerability, and nonglycemic effects of incretin-based therapies
TAKE-HOME POINTS
- Patient education, which is essential for successful patient self-management, can be provided by a multidisciplinary diabetes care team
- The dosing and administration of glucagon-like peptide (GLP)-1 agonists or dipeptidyl peptidase (DPP)-4 inhibitors offer significant flexibility to meet patient needs
- The GLP-1 agonists and DPP-4 inhibitors vary in administration, effect on weight, contraindications, and dosing adjustments for patients with renal impairment
- The relatively high cost ($7 to $14 per day) of therapy with a GLP-1 agonist or DPP-4 inhibitor may be covered by insurance, so cost to the patient may be limited to copays
The authors received editorial assistance from the Primary Care Education Consortium and WriteHealth, LLC in the development of this activity and honoraria from the Primary Care Education Consortium. They have disclosed that Dr Campbell is on the advisory board for Daiichi-Sankyo and the speakers bureau for Eli Lilly and Co; Dr Cobble is on the advisory board for Abbott Laboratories, AstraZeneca, and Eli Lilly and Co and speakers bureau for Abbott Laboratories, AstraZeneca/Bristol Myers Squibb, Eli Lilly and Co, GlaxoSmithKline, and Novo Nordisk Inc; Dr Reid is on the advisory board and speakers bureau for Amylin Pharmaceuticals, Medtronic, Novo Nordisk Inc, and sanofi-aventis; and Dr Shomali is on the advisory board for Novo Nordisk Inc and speakers bureau for Amylin Pharmaceuticals, Eli Lilly and Co, sanofi-aventis, and Takeda Pharmaceuticals.
Introduction
The comprehensive and long-term management of patients with type 2 diabetes mellitus (T2DM) requires that they assume primary responsibility for daily self-management. For this to occur, patient education is critical, yet it is time-consuming. Because our time as primary care physicians is limited, developing a diabetes care team, even informally, can be helpful in providing the comprehensive care that is needed. Beyond easing the amount of time we need to provide the patient education required, the patient is able to benefit from the specialized skills and knowledge of other team members, such as a nurse, pharmacist, dietitian, certified diabetes educator, or an exercise specialist. It is important, however, that as primary care physicians, we coordinate the care provided by the team so that treatment goals are clear, communication is maintained, and patient outcomes are optimal.
With this need for patient self-management supported by ongoing education in mind, let’s turn our attention to some issues of special importance with respect to the GLP-1 agonists and DPP-4 inhibitors.
Dosing and administration
There is considerable variability among the GLP-1 agonists and DPP-4 inhibitors with respect to their dosing and administration (TABLE).1-4 This variability enables you and your patients to select a treatment that best meets their needs.
Case 2
As you begin to talk about the GLP-1 agonists and DPP-4 inhibitors as treatment options for modifying his therapy, this 47-year-old office manager wants to know what side effects are likely and which, if any, might pose a problem at work.
You can begin by telling the patient that transient nausea has been a common occurrence in patients treated with a GLP-1 agonist and that a key factor regarding this side effect is how the medication is titrated (see accompanying article “Safety, tolerability, and nonglycemic effects of incretin-based therapies”). Exenatide and liraglutide should be administered using the dose escalation strategy outlined in the TABLE. You tell him that nausea is typically mild and usually peaks within 8 weeks of commencing treatment with exenatide5 and within 4 to 6 weeks with liraglutide.6,7 Should nausea persist and be troublesome, taking liraglutide with food has been helpful for some patients; otherwise, liraglutide can be taken at the same time each day irrespective of meals.2 You also note that saxagliptin and sitagliptin can be taken with or without food.3,4 While the prescribing information indicates that exenatide can be taken at any time within the 60-minute period before a meal,1 exenatide can be administered during but not after the meal if necessary to reduce nausea, without sacrificing its glucose-lowering effects8; the satiety effect, however, may be blunted in some patients. Reduction in the postprandial glucose level has been shown to be greatest when exenatide is taken between 60 minutes before or by the end of the meal. Exenatide should not be taken after the meal, because transient low blood glucose levels may occur.8
In patients with renal dysfunction, the dose of sitagliptin and saxagliptin but not liraglutide needs to be adjusted (TABLE).1-4 Exenatide should not be used in patients with a CrCl <30 mL/min. Exenatide and sitagliptin are contraindicated in patients with a known hypersensitivity reaction to the drug.1,3 Liraglutide is contraindicated in patients with a personal or family history of medullary thyroid cancer or in patients with multiple endocrine neoplasia (MEN) syndrome type 2.2 There are no contraindications listed for saxagliptin.4