Research Performed
This article describes a meta-analysis of three clinical trials that were performed over 30-weeks and controlled using a placebo (Bond, 2006). This study reviews the outcomes of using exenatide as an adjunct to first-line medication including sulfonylurea and/or metformin, for treatment of type II diabetes mellitus in adults.
Metmorfin vs. Exenatide
The first study evaluated the effects of using exenatide as an adjunct to metformin (DeFronzo, Ratner, Han, Kim, Fineman, & Baron, 2005). The study, which adopted a triple-blind design, used four treatment arms. These treatment arms included two placebo arms of metformin monotherapy, metformin combined with a 5 mcg dose of exenatide bid; and metformin with a 10 mcg dose of exenatide bid (5 mcg dose increased to 10 mcg dose subsequent to the first 4-weeks of the study). The subjects did not all maintain to the end as several withdrew from the study. The researchers used hemoglobin A1c as a variable for measuring glycemic control and safety associated with the use of the new intervention (Bond, 2006).
The finding of the study was positive for the two arms that applied exenatide as an adjunct to metformin. The arms that used a 10 mcg dose of exenatide indicated a greater reduction in glycemic activity and body weight of the subjects than that which used a 5 mcg dose (Bond, 2006).
Sulfonylurea vs. Exenatide
The second study evaluated the outcome of using sulfonylurea monotherapy and sulfonylurea with exenatide as an adjunct (Buse, Henry, Han, Kim, Fineman, & Baron, 2004). This study adopted a triple-blind design in which the effects of the adjunct were controlled using a placebo. The researchers standardized therapy by putting all patients into a placebo lead-in over a period of four weeks. The subjects were on different kinds of drugs of the sulfonylurea group.
Similar to the study by DeFronzo et al. (2005), the authors studied four arms of treatment, including sulfonylurea uncombined (two arms), sulfonylurea with the adjunct 5 mcg dose bid, and sulfonylurea with the adjunct 10 mcg dose bid (5 mcg dose increased to 10 mcg dose at the start of the fifth study-week). At the end of the 30-week study period, fewer subjects completed the study than there were at the initiation of the study; however, the withdrawal rates did not have significant effects on the outcome.
The two exenatide arms indicated a reduction in HbA1c at P < 0.001. However, the percentage reduction in glycemic activity differed. The 10 mcg dose arm indicated a greater reduction of HbA1c and weight than the 5 mcg dose arm (Buse et al., 2004).
Metformin Combined with Sulfonylurea vs. Exenatide
Bond (2006) performed a systematic review of a study by Kendall et al. (2005). Kendal et al. (2005) analyzed the effects of exenatide as an adjunct to a combination of metformin and sulfonylurea against the combination of the same drugs without the adjunct (exenatide). The study adopted a randomized, double-blind design that was controlled using a placebo. Like the mentioned two studies, this study used glycemic control represented by HbA1c and safety as dependent variables for the outcomes of the new intervention.
The authors studied four arms of the treatment. One arm included a combination of metformin and sulfonylurea with placebo (two arms). A third arm involved metformin, sulfonylurea and the adjunct at 5 mcg dose bid. A fourth arm involved metformin, sulfonylurea and the adjunct 10 mcg dose bid (5 mcg dose was increased to 10 mcg dose in the subsequent weeks after the first 4 weeks). Like the mentioned two studies, some subjects withdrew from the study as of the end of the 30-weeks of study; although, the effects of the withdrawal were not statistically significant in all of the arms.
The authors observed reductions in HbA1c and weight for the two exenatide arms, although the difference in the reductions of HbA1c between the two arms was smaller than when metformin and sulfonylurea were used separately. In fact, the two arms indicated the same change in weight of –1.6 ±0.2 kg relative to the arm with a placebo of –0.9 ±0.2 kg, after the 30-week period.
Clinical Findings and Significance to Nursing Practice
Contraindications and Adverse Effects
Exenatide has numerous events for which it is contraindicated. This situation means that nurses must have full knowledge of the contraindications to ensure the safety of type II diabetic Mellitus patients. In the same line, they must ensure that they have full knowledge of every patient’s medical history with which they get involved. In addition, they must maintain and pass an accurate medical history of their diabetic patients between shifts to ensure patient safety.
Exenatide application was associated with mild or moderate side effects, with nausea as the most common of all the effects. Nevertheless, the severity of nausea was reduced with progressive administration and was dependent on dose. In this vein, nurses should be equipped with interventions for managing side effects of exenatide to correct nausea, vomiting and diarrhea in diabetic patients using exenatide in adjunct treatment of type 2 diabetes mellitus. Because exenatide does not cause hypoglycemia when used in the treatment of type II diabetes mellitus (Bond, 2006), nurses should use it as a choice drug in preference over insulin.
Dosing, Administration and Drug Interaction
The proposed initial dose for the use of adjunct in the treatment of diabetes mellitus type II is 5 mcg for every dose given subcutaneously bid, an hour prior to breakfast and dinner. However, a nurse may increase the dose to 10 mcg bid after one month if the effect of the first dose is insignificant. The sites of administration include the upper arm, thigh, and abdomen (Bond, 2006). Depending on the first-line agents used, the nurses must know when the dose adjustment of the adjunct is appropriate and when it is not.
Exenatide influences the bioavailability of oral medications by reducing the rate of gastric emptying. Therefore, nurses must be cautious to administer oral drugs whose bioavailability depends on gastric emptying at least an hour following administration of exenatide (Bond, 2006).
References
Bond, A. (2006). Exenatide (Bettal) As a Novel Treatment Option for Type 2 Diabetes Mellitus. Proc (Bayl Univ Med Cent) , 19, 281-284.
Buse, J. B., Henry, R. R., Han, J., Kim, D. D., Fineman, M. S., & Baron, A. D. (2004). Exenatide-113 Clinical Study Group. Effects of Exenatide (Exendin-4) on Glycemic Control Over 30 Weeks in Sulfonylurea-treated Patients with Type 2 Diabetes. Diabetes Care, 27 (11), 2628-2635.
DeFronzo, R. A., Ratner, R. E., Han, J., Kim, D. D., Fineman, M. S., & Baron, A. D. (2005). Effects of Exenatide (Exendin-4) on Glycemic Control and Weight Over 30 Weeks in Metformin-treated Patients with Type 2 Diabetes. Diabetes Care, 28 (5), 1092-1100.
Kendall, D. M., Riddle, M. C., Rosenstock, J., Zhuang, D., Kim, D. D., Fineman, M. S., et al. (2005). Effects of Exenatide (Exendin-4) on Glycemic Control Over 30 Weeks in Patients with Type 2 Diabetes. Diabetes Care, 28 (5), 1083-1091.