REVIEW
Basal-bolus insulin therapy and glycemic control in adult patients with type 2 diabetes mellitus: A review of the literature Bridget Jackson, RN, MSN (Assistant Professor)1 & Laurie Grubbs, PhD, ARNP (Professor)2 1 2
Florida Hospital College of Health Sciences, Orlando, Florida College of Nursing, Florida State University, Tallahassee, Florida
Keywords Insulin; basal-bolus insulin therapy; blood glucose; glycemic control; diabetes mellitus; type 2; adult. Correspondence Laurie Grubbs, PhD, ARNP, College of Nursing, Florida State University, 98 Varsity Way, P.O. Box 4310, Duxbury Hall, Tallahassee, FL 32306-4310. Tel: 850-644-5363; Fax: 850-644-7660; E-mail: [email protected] Received: June 2012; accepted: June 2012 doi: 10.1002/2327-6924.12033
Abstract Purpose: To present an integrative review related to basal-bolus insulin therapy and glycemic control in adult patients with type 2 diabetes mellitus. Data sources: A search of the Cochrane, Medline (first search and PubMed), and CINAHL electronic databases was conducted from 2004 through 2011 using the search terms “basal-bolus insulin therapy, sliding scale insulin, glycemic control, and adult.” Conclusions: Comparisons were made of glycemic control, safety, adverse events, body weight, and insulin dose showing basal-bolus insulin therapy to be at least equal, if not superior to sliding scale insulin for the patient with type 2 diabetes mellitus. Overall patients using basal-bolus insulin therapy experienced better glycemic control, fewer hypoglycemic events, and had less weight gain. Implications for practice: Basal-bolus insulin therapy is recommended over sliding scale insulin for achieving glycemic control in both the inpatient and outpatient setting because of a reduced number of occurrences of hyper- or hypoglycemic events. This could translate to decreased hospitalizations, decreased length of stay, decreased healthcare costs, and improved patient outcomes.
Current treatment In type 2 diabetes mellitus (DM), the pancreas may produce insulin but in insufficient amounts, or its utilization is impaired. Over time, the pancreas will cease to produce any insulin, which leads to the need for exogenous insulin (Miser et al., 2010; Raskin, Gylvin, Weng, & Chaykin, 2009). In the healthy adult, insulin is continuously emitted from the β-cells in the islets of Langerhans in small doses, called a basal rate. When food is ingested, the rate of emission of insulin is increased and is known as a bolus. Historically, sliding scale insulin (SSI) has been used for bolus therapy with doses determined by algorithms using blood glucose (BG) targets (Umpierrez et al., 2007). Recently, SSI therapy has been deemed a reactive and ineffective method in the management of hyperglycemia because it does not take into consideration previously administered insulin or dietary intake and therefore, predisposes to hyper- and hypoglycemia (Hassan, 2007). Basal-bolus insulin therapy (BBT) is currently recommended for type 2 DM because it is a more
348
proactive approach that mimics the body’s normal physiologic patterns of endogenous insulin secretion (Pollom, 2010). It is recommended to split the insulin into basal 50% and bolus 50% (Hassan, 2007). An intermediate or long-acting insulin analog is used to mimic the basal insulin emission from the pancreas (glargine or detemir once daily). The duration of long-acting insulin analogs is 20–24 h with little or no peak. It can be given once daily rather than the twice daily dosing of NPH with a duration of 12–18 h. The rapid or short-acting insulin analogs (aspart, glulisine, lispro) are used before meals three times daily to mimic the bolus. The shorter onset of rapid-acting analog insulin (15 min) allows it to be given with a meal, which is helpful with irregular meal times and irregular caloric intake for both inpatient and outpatient settings. The shorter time to peak effect of rapid-onset analogs (30–90 min) minimizes postprandial hyperglycemia, and their shorter duration of action (4– 6 h) reduces the risk of between-meal hypoglycemia (Moghissi, 2010).
C 2013 The Author(s) Journal of the American Association of Nurse Practitioners 26 (2014) 348–352 C 2013 American Association of Nurse Practitioners
Basal-bolus insulin therapy
B. Jackson & L. Grubbs
Literature review A search of the Cochrane, Medline (first search and PubMed), and CINAHL electronic databases was conducted covering the years from 2004 through 2011. Search terms used were basal-bolus insulin therapy, sliding scale insulin, glycemic control, and adult. Articles were included if they contained the words “basal-bolus,” “basal insulin,” “basal-bolus insulin therapy/regimen” in the title or the abstract. Articles were excluded if they addressed changes in basal therapy related to surgery, maternal glycemic control, continuous subcutaneous insulin infusions, inhaled insulin, insulin pumps, or continuous glucose monitoring. This article focuses only on the efficacy of BBT in adult type 2 DM; type 1 DM patients were not included. The results from seven prospective, randomly controlled trials; two retrospective, randomized studies; and two review articles are presented (Chen, Steinke, Karounos, Lane, & Matson, 2010; Fritsche, Larbig, Owens, & Haring, 2010; Hollander, Cooper, Brehnoj, & Pedersen, 2008; Johnston & Van Horn, 2011; Miser et al., 2010; Moghissi, 2010, Pollom, 2010; Raskin et al., 2009; Selam & Meneghini, 2009; Umpierrez et al., 2007, 2011). See Table S1 for complete details of the studies. The common themes found in the studies were glycemic control, safety, adverse events (AEs), body weight, insulin type, and insulin dose. One study compared basal-bolus therapy with insulin lispro premixed therapy as initiation insulin in type 2 DM (Miser et al., 2010). A similar study compared basal-bolus therapy with premix NPH/regular or premix NPH/lispro or aspart in patients previously taking Premix insulin (Fritsche et al., 2003). Two studies compared insulin detemir with insulin glargine in a basal-bolus regimen (Hollander et al., 2008; Raskin et al., 2009). Four more studies compared basal-bolus therapy (BBT) with SSI therapy (Chen et al., 2010; Johnston & Van Horn, 2011; Umpierrez et al., 2007, 2011). Two review articles examined types and schedules for insulin to achieve optimal glycemic control while increasing safety by minimizing significant episodes of hypoglycemia (Moghissi, 2010; Pollom, 2010). One study compared the safety and efficacy of insulin detemir using the 303 Algorithm in the US PREDICTIVE 303 trial (Selam & Meneghini, 2009). The 303 Algorithm allows patients to self-adjust detemir insulin every 3 days, plus or minus 3 units if mean fasting plasma glucose is above 110 mg/dL or below 80 mg/dL.
Glycemic control The term ”glycemic control” refers to the management of the BG level to keep it at a normal or near normal level in order to prevent injury to tissues and organs. Re-
searchers monitored the BG concentration before each meal and at bedtime using a glucose meter and found that patients treated with insulin glargine (Lantus) and glulisine (Apidra) had greater improvement in glycemic control than those treated with SSI. Treatment with SSI was associated with higher mean fasting glucose, mean random glucose, and mean glucose during hospital stay in both medical and surgical patients (Umpierrez et al., 2007, 2011). Fritsche et al. (2010) found BBT superior to Premix insulin for reduction in HbA1c and achievement of target HbA1c < 7%, as well as greater reduction in postprandial BG and daytime BG compared to premix therapy. Chen et al. (2010) found higher median BG measurements with BBT versus SSI, but lower hypoglycemic events. The review articles by Moghissi (2010) and Pollom (2010) recommended BBT plus correction insulin over SSI for improved glycemic control and decreased hypoglycemic events. Two of the studies were equivocal. Miser et al. (2010) found no significant difference in HbA1c or incidence of hypoglycemia between arms or groups from baseline to study completion at 6 months. A retrospective study by Johnston and Van Horn (2011) found poor glucose control overall with higher mean BG values in the BBT plus correction group compared to the SSI group, with a 2% hypoglycemic rate in the SSI group only. Two studies compared the insulin analogues detemir and glargine in a basal-bolus regimen (Hollander et al., 2008; Raskin et al., 2009). Hollander et al. (2008) found that 36.2% of the patients treated with insulin detemir and 36.7% of the patients treated with insulin glargine achieved an HbA1c ≤ 7% with no significant difference between the groups. They also found no significant difference in mean fasting plasma glucose (FPG) between the detemir and glargine groups. Raskin et al. (2009) found that the HbA1c showed a significant decrease from baseline in both treatment groups. A third study found that patients using insulin detemir with the 303 Algorithm achieved a greater reduction in FPG, both groups achieved similar reductions in HbA1c (Selam & Meneghini, 2009).
Safety Safety was specifically addressed in terms of hypoglycemia, as “hypoglycemia has been shown to be an independent risk factor for mortality” (Moghissi, 2010, p. 501). Umpierrez et al. (2007) compared a basal-bolus insulin regimen with that of sliding scale regular insulin (SSI) in medical patients with type 2 DM and reported only two patients in each treatment group experienced hypoglycemia (≤60 mg/dL). Out of 2026 glucose readings, none of the readings were
Basal-bolus insulin therapy and glycemic control in adult patients with type 2 diabetes mellitus: A review of the literature Bridget Jackson, RN, MSN (Assistant Professor)1 & Laurie Grubbs, PhD, ARNP (Professor)2 1 2
Florida Hospital College of Health Sciences, Orlando, Florida College of Nursing, Florida State University, Tallahassee, Florida
Keywords Insulin; basal-bolus insulin therapy; blood glucose; glycemic control; diabetes mellitus; type 2; adult. Correspondence Laurie Grubbs, PhD, ARNP, College of Nursing, Florida State University, 98 Varsity Way, P.O. Box 4310, Duxbury Hall, Tallahassee, FL 32306-4310. Tel: 850-644-5363; Fax: 850-644-7660; E-mail: [email protected] Received: June 2012; accepted: June 2012 doi: 10.1002/2327-6924.12033
Abstract Purpose: To present an integrative review related to basal-bolus insulin therapy and glycemic control in adult patients with type 2 diabetes mellitus. Data sources: A search of the Cochrane, Medline (first search and PubMed), and CINAHL electronic databases was conducted from 2004 through 2011 using the search terms “basal-bolus insulin therapy, sliding scale insulin, glycemic control, and adult.” Conclusions: Comparisons were made of glycemic control, safety, adverse events, body weight, and insulin dose showing basal-bolus insulin therapy to be at least equal, if not superior to sliding scale insulin for the patient with type 2 diabetes mellitus. Overall patients using basal-bolus insulin therapy experienced better glycemic control, fewer hypoglycemic events, and had less weight gain. Implications for practice: Basal-bolus insulin therapy is recommended over sliding scale insulin for achieving glycemic control in both the inpatient and outpatient setting because of a reduced number of occurrences of hyper- or hypoglycemic events. This could translate to decreased hospitalizations, decreased length of stay, decreased healthcare costs, and improved patient outcomes.
Current treatment In type 2 diabetes mellitus (DM), the pancreas may produce insulin but in insufficient amounts, or its utilization is impaired. Over time, the pancreas will cease to produce any insulin, which leads to the need for exogenous insulin (Miser et al., 2010; Raskin, Gylvin, Weng, & Chaykin, 2009). In the healthy adult, insulin is continuously emitted from the β-cells in the islets of Langerhans in small doses, called a basal rate. When food is ingested, the rate of emission of insulin is increased and is known as a bolus. Historically, sliding scale insulin (SSI) has been used for bolus therapy with doses determined by algorithms using blood glucose (BG) targets (Umpierrez et al., 2007). Recently, SSI therapy has been deemed a reactive and ineffective method in the management of hyperglycemia because it does not take into consideration previously administered insulin or dietary intake and therefore, predisposes to hyper- and hypoglycemia (Hassan, 2007). Basal-bolus insulin therapy (BBT) is currently recommended for type 2 DM because it is a more
348
proactive approach that mimics the body’s normal physiologic patterns of endogenous insulin secretion (Pollom, 2010). It is recommended to split the insulin into basal 50% and bolus 50% (Hassan, 2007). An intermediate or long-acting insulin analog is used to mimic the basal insulin emission from the pancreas (glargine or detemir once daily). The duration of long-acting insulin analogs is 20–24 h with little or no peak. It can be given once daily rather than the twice daily dosing of NPH with a duration of 12–18 h. The rapid or short-acting insulin analogs (aspart, glulisine, lispro) are used before meals three times daily to mimic the bolus. The shorter onset of rapid-acting analog insulin (15 min) allows it to be given with a meal, which is helpful with irregular meal times and irregular caloric intake for both inpatient and outpatient settings. The shorter time to peak effect of rapid-onset analogs (30–90 min) minimizes postprandial hyperglycemia, and their shorter duration of action (4– 6 h) reduces the risk of between-meal hypoglycemia (Moghissi, 2010).
C 2013 The Author(s) Journal of the American Association of Nurse Practitioners 26 (2014) 348–352 C 2013 American Association of Nurse Practitioners
Basal-bolus insulin therapy
B. Jackson & L. Grubbs
Literature review A search of the Cochrane, Medline (first search and PubMed), and CINAHL electronic databases was conducted covering the years from 2004 through 2011. Search terms used were basal-bolus insulin therapy, sliding scale insulin, glycemic control, and adult. Articles were included if they contained the words “basal-bolus,” “basal insulin,” “basal-bolus insulin therapy/regimen” in the title or the abstract. Articles were excluded if they addressed changes in basal therapy related to surgery, maternal glycemic control, continuous subcutaneous insulin infusions, inhaled insulin, insulin pumps, or continuous glucose monitoring. This article focuses only on the efficacy of BBT in adult type 2 DM; type 1 DM patients were not included. The results from seven prospective, randomly controlled trials; two retrospective, randomized studies; and two review articles are presented (Chen, Steinke, Karounos, Lane, & Matson, 2010; Fritsche, Larbig, Owens, & Haring, 2010; Hollander, Cooper, Brehnoj, & Pedersen, 2008; Johnston & Van Horn, 2011; Miser et al., 2010; Moghissi, 2010, Pollom, 2010; Raskin et al., 2009; Selam & Meneghini, 2009; Umpierrez et al., 2007, 2011). See Table S1 for complete details of the studies. The common themes found in the studies were glycemic control, safety, adverse events (AEs), body weight, insulin type, and insulin dose. One study compared basal-bolus therapy with insulin lispro premixed therapy as initiation insulin in type 2 DM (Miser et al., 2010). A similar study compared basal-bolus therapy with premix NPH/regular or premix NPH/lispro or aspart in patients previously taking Premix insulin (Fritsche et al., 2003). Two studies compared insulin detemir with insulin glargine in a basal-bolus regimen (Hollander et al., 2008; Raskin et al., 2009). Four more studies compared basal-bolus therapy (BBT) with SSI therapy (Chen et al., 2010; Johnston & Van Horn, 2011; Umpierrez et al., 2007, 2011). Two review articles examined types and schedules for insulin to achieve optimal glycemic control while increasing safety by minimizing significant episodes of hypoglycemia (Moghissi, 2010; Pollom, 2010). One study compared the safety and efficacy of insulin detemir using the 303 Algorithm in the US PREDICTIVE 303 trial (Selam & Meneghini, 2009). The 303 Algorithm allows patients to self-adjust detemir insulin every 3 days, plus or minus 3 units if mean fasting plasma glucose is above 110 mg/dL or below 80 mg/dL.
Glycemic control The term ”glycemic control” refers to the management of the BG level to keep it at a normal or near normal level in order to prevent injury to tissues and organs. Re-
searchers monitored the BG concentration before each meal and at bedtime using a glucose meter and found that patients treated with insulin glargine (Lantus) and glulisine (Apidra) had greater improvement in glycemic control than those treated with SSI. Treatment with SSI was associated with higher mean fasting glucose, mean random glucose, and mean glucose during hospital stay in both medical and surgical patients (Umpierrez et al., 2007, 2011). Fritsche et al. (2010) found BBT superior to Premix insulin for reduction in HbA1c and achievement of target HbA1c < 7%, as well as greater reduction in postprandial BG and daytime BG compared to premix therapy. Chen et al. (2010) found higher median BG measurements with BBT versus SSI, but lower hypoglycemic events. The review articles by Moghissi (2010) and Pollom (2010) recommended BBT plus correction insulin over SSI for improved glycemic control and decreased hypoglycemic events. Two of the studies were equivocal. Miser et al. (2010) found no significant difference in HbA1c or incidence of hypoglycemia between arms or groups from baseline to study completion at 6 months. A retrospective study by Johnston and Van Horn (2011) found poor glucose control overall with higher mean BG values in the BBT plus correction group compared to the SSI group, with a 2% hypoglycemic rate in the SSI group only. Two studies compared the insulin analogues detemir and glargine in a basal-bolus regimen (Hollander et al., 2008; Raskin et al., 2009). Hollander et al. (2008) found that 36.2% of the patients treated with insulin detemir and 36.7% of the patients treated with insulin glargine achieved an HbA1c ≤ 7% with no significant difference between the groups. They also found no significant difference in mean fasting plasma glucose (FPG) between the detemir and glargine groups. Raskin et al. (2009) found that the HbA1c showed a significant decrease from baseline in both treatment groups. A third study found that patients using insulin detemir with the 303 Algorithm achieved a greater reduction in FPG, both groups achieved similar reductions in HbA1c (Selam & Meneghini, 2009).
Safety Safety was specifically addressed in terms of hypoglycemia, as “hypoglycemia has been shown to be an independent risk factor for mortality” (Moghissi, 2010, p. 501). Umpierrez et al. (2007) compared a basal-bolus insulin regimen with that of sliding scale regular insulin (SSI) in medical patients with type 2 DM and reported only two patients in each treatment group experienced hypoglycemia (≤60 mg/dL). Out of 2026 glucose readings, none of the readings were
