Dialogue and Diagnosis - American Osteopathic Association

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during the day with each meal. Increasing basal insulin doses in such cases may not improve glucose control and may lead to increased weight and the risk of hypoglycemia. Insulin resistance, -cell failure, and over-basalization put the physician at a critical point on the decision tree of diabetes management. Often the approach to patients not achieving treatment goals with basal insulin analogs is to add 1 or more doses of prandial insulin in the form of a rapid-acting insulin analog (eg, insulin aspart, insulin lispro, or insulin glulisine) or regular human insulin. 13 Although many physicians consider multiple-injection basalbolus therapy to be the “gold standard,” addition of a single prandial dose to basal insulin therapy can bring many patients to goal in a simpler and more patient-friendly manner. The Orals Plus Apidra and LANTUS (OPAL) study 18 showed that addition of a single bolus of rapidacting insulin analog, administered at either breakfast or main mealtime in combination with basal insulin and oral antidiabetic drugs, resulted in a decrease in HbA 1c level from 7.32% to 6.99% (P.001). Meneghini and colleagues 19 compared 2 intensification strategies for stepwise addition of prandial insulin analogs in patients whose T2DM was inadequately controlled by basal insulin detemir. They found an overall reduction in HbA 1c of 1.2% with stepwise addition of rapid-acting insulin analogs to 1 or more meals, regardless of whether preprandial or postprandial glucose levels were the target of titration efforts. Limitations of adding prandial insulin to improve glycemic control include its greater complexity for patients to self-titrate, its increased risk of hypoglycemia, and its likelihood of leading to weight gain. 20 Another choice for improving glycemic control would be use of a premixed insulin analog. However that option is probably even less desirable for Gloria because, to be most effective and tolerated, it necessitates strict regularity in mealtimes and meal carbohydrate content. Furthermore, weight gain is more common with premixed insulin supplementation than with the basal bolus insulin regimen previously discussed. 19 Pramlintide, an amylinomimetic, is approved for use in insulin-treated patients who have either type 1 diabetes mellitus (T1DM) or T2DM and elevated PPG levels. Pramlintide is cosecreted with insulin from pan creatic -cells and acts centrally to slow gastric emptying, suppress postprandial glucagon secretion, and decrease food intake. These actions comple ment those of insulin to regulate blood glucose concentrations. Pramlintide is associated with modest beneficial effects on HbA 1c levels when used as adjunctive therapy. Pramlintide is effective at stabilizing blood glucose levels and, once the appropriate dosage is established, it is an effective tool in managing T1DM and T2DM. Pramlintide is also associated with weight loss, which may be attractive, but it carries with it an increased risk of hypoglycemia and it requires an additional injection before every meal. Nausea is a common adverse effect of this medication. 21 A patient education support program may be needed for successful use of this agent. Pramlintide was not considered the best choice for Gloria. Basal insulin in combination with incretin-based therapies A major challenge to implementing intensive therapy in patients with 26 Dialogue and Diagnosis // September 2012
T2DM is achieving glycemic control without undue risk of hypoglycemia or weight gain. A new approach would be to consider incretin-based agents, which are not associated with weight gain and which work in a glucose-dependent manner (ie, only in the presence of hyperglycemia). Basal insulin and incretin-based agents are complementary therapies for patients with T2DM—insulin corrects the basic pathophysiologic defect and incretin-based agents improve insulin secretion while decreasing glucagon output. Combining an incretin-based therapy with insulin is an attractive treatment option for Gloria. This combination has the potential to maximize glycemic control while minimizing the risk of hypoglycemia, to ameliorate the weight gain typical of insulin therapy, and—in patients on established insulin therapy—to decrease insulin dose requirements when used with a glucagon-like peptide-1 (GLP-1) receptor agonist. Insulin and DPP-4 inhibitors in combination DPP-4 inhibitors are oral agents that work by inhibiting the enzyme that degrades native GLP-1 and thus support maintaining what levels of GLP-1 are still available in patients with T2DM. As such, they are associated with modest reductions in A1c, and are often used as part of combination therapy strategies, but can be used as monotherapy in patients without marked hyperglycemia. These agents, sitagliptin, saxagliptin, and linagliptin are not associated with weight gain or with nausea, and are generally well tolerated. Of the DPP-4 inhibitors, sita - gliptin is currently the only agent approved for use with insulin. Although not paralleling our patient’s case directly, the TRANSITION study examined whether patients using metformin with or without other oral agents and who were not at treat - ment goals would do better with the addition of sitagliptin with or without a sulfonylurea, or sitagliptin with or without a basal insulin (insulin detemir). 22 The combination of oncedaily insulin detemir with sitagliptin showed clinically and statistically significant better improve ment in glycemic control compared to sita - gliptin with or without a sulfonylurea (P.001). Saxaglitpin also improves glycemic control in patients whose glucose levels are poorly controlled on insulin alone or on insulin and metformin. A placebo-subtracted HbA 1c reduction of 0.41% was observed in a study by Barnett et al. 23 When saxagliptin and other DPP-4 inhibitors are used in combination with a sulfonylurea or with insulin, medications known to cause hypoglycemia, the incidence of confirmed hypoglycemia may be increased. Therefore, a lower dose of insulin secretagogue or insulin may be required to minimize the risk of hypoglycemia when used in combination with DPP-4 inhibitors. Linagliptin has not been studied in combination with insulin therapy. Insulin and GLP-1 receptor agonists in combination Another option that requires subcutaneous injections—but fewer injec - tions than basal bolus insulin— include the GLP-1 receptor agonists. There are 3 currently available GLP-1 receptor agonists: exenatide twice daily, liraglutide once daily, and exenatide extended release once weekly. Exenatide twice daily and liraglutide once daily are approved for use with basal insulin. The concomitant use of a GLP-1 receptor agonist and insulin may be advantageous for mitigating the weight gain associated with insulin therapy. This is particularly true for obese patients with longstanding T2DM, as is the scenario in Dialogue and Diagnosis // September 2012 27
Page 1 and 2: Volume 2 Number 2 September 2012 In
Page 3 and 4: Introducing and adjusting injectabl
Page 5 and 6: the fact that he was obviously upse
Page 7 and 8: insulin therapy include a sense of
Page 9 and 10: Basal insulin alone Sequential addi
Page 11 and 12: speaking Hispanic patients reported
Page 13 and 14: AFTER METFORMIN Introducing and tit
Page 15 and 16: Figure 1. The simultaneously increa
Page 17 and 18: Figure 3. Key benefits and risks of
Page 19 and 20: Compounds Exenatide (approved 2005
Page 21 and 22: PATIENT DIALOGUE Are GLP-1 receptor
Page 23 and 24: missed and the next scheduled dose
Page 25 and 26: Adding glucagon-like peptide-1 rece
Page 27: hips, which, with her excess weight
Page 31 and 32: Patient instruction Clearly discuss
Page 33 and 34: 8-point glucose levels) and did so
Page 35 and 36: InsideOut (continued from inside fr

Dialogue and Diagnosis - American Osteopathic Association

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