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Is Sitagliptin Plus Glargine Noninferior to Basal–Bolus Insulin for Inpatient Management of Type 2 Diabetes?
Study Overview
Objective. To compare the safety and efficacy of basal–bolus insulin therapy with sitagliptin plus insulin glargine in type 2 diabetes patients admitted to general medicine and surgical wards.
Design. Multicenter, prospective, open-label, noninferiority randomized clinical trial.
Setting and participants. Type 2 diabetes patients aged 18 to 80 years admitted to the general medicine and surgery services at one of 5 academic-based US hospitals were recruited. Eligible participants presented with a random blood glucose concentration between 140 and 400 mg/dL and were treated at home with diet, oral agents, or oral agents plus insulin at a maximum daily dose of 0.6 units/kg. Among those excluded were patients recently treated with a dipeptidyl peptidase-4 (DPP-4) inhibitor or glucagon-like peptide-1 (GLP-1) agonist, patients with clinically relevant hepatic disease, patients who were not eating for more than 48 hours, and those with an estimated glomerular filtration rate (eGFR) < 30 mL/min.
Intervention. Participants were randomly assigned to receive basal–bolus insulin therapy (BBI) with glargine once daily plus rapid-acting insulin before meals or sitagliptin plus glargine (SPG) once daily. Those in the SPG group received sitagliptin 100 mg/day if their eGFR was > 50 mL/min and sitagliptin 50 mg/day if their eGFR was 30 to 50 mL/min. If the eGFR fell below 30 mL/min during the hospitalization, sitagliptin was reduced to 25 mg/day. Glargine doses for those in the SPG group were started at 0.2 units/kg if randomization blood glucose was 140–200 mg/dL and 0.25 units/kg if randomization glucose was 201–400 mg/dL. Patients aged 70 or older or with an eGFR < 50 mL/min started with a daily glargine dose of 0.15 units/kg. For the BBI group, a total daily insulin dose of 0.4 units/kg was initiated for those with blood glucose levels between 140 and 200 mg/dL, and 0.5 units/kg for those with randomization glucose between 201 and 400 mg/dL. Half of this daily dose was given as glargine and the other half was distributed evenly across 3 pre-meal doses. Both the BBI and SPG groups received pre-meal and bedtime correction doses of rapid-acting insulin for glucose levels above 140 mg/dL. Blood glucose concentrations were measured fasting, before meals, and at bedtime or every 6 hours for patients who were not eating. Target fasting and pre-meal blood glucose levels were 100 to 140 mg/dL. Investigators and participants were not blinded to group assignment and glucose control was managed by the primary medical or surgical team.
Main outcomes measure. The primary outcome for this trial was noninferiority for differences between the SPG and BBI groups in glycemic control. Secondary endpoints included differences in the number of hypoglycemic and hyperglycemic events, the number of blood glucose values between 70 and 140 mg/dL and between 70 and 180 mg/dL, and the number of treatment failures (defined as 2 consecutive blood glucose values > 240 mg/dL or mean daily glucose > 240 mg/dL), length of hospital stay, total daily dose of insulin, number of insulin injections per day, transfer to the intensive care unit, and hospital complications and mortality.
Main results. A total of 138 patients in the SPG group and 139 patients in the BBI group completed the study and were included in this analysis. Of these 277 patients, 84% were admitted to a medicine ward and 16% were admitted to a surgical ward. The average age of participants was approximately 57 years, the average BMI was approximately 35 kg/m2, and the average duration of diabetes was approximately 10 years. These baseline characteristics as well as ethnic origin, sex, and baseline A1c (approximately 40% of patients in both groups had a baseline A1c between 7% and 9%) did not differ between groups. Prior to admission, approximately 40% of patients in both groups were managed with oral drugs alone, approximately 25% were managed with insulin alone, and about 22% were managed with insulin and oral therapy.
With respect to the primary outcome, both groups had similar mean daily blood glucose concentrations (171 mg/dL in SPG and 169 mg/dL in BBI) throughout the hospitalization, meeting the noninferiority threshold for glycemic control between groups. As for secondary outcomes, the mean proportion of blood glucose readings between 70 and 140 mg/dL, 70 and 180 mg/dL, and 100 and 140 mg/dL did not differ between groups. Pre-meal and bedtime blood glucose concentrations were also similar in both groups. There was a significant difference between groups in average daily insulin dose (24 units in SPG versus 34 units in BBI), total units of insulin per kg per day (0.2 units/kg in SPG versus 0.3 units/kg in BBI), and number of insulin injections per day (2.2 in SPG versus 2.9 in BBI). There was no difference in the number of hypoglycemic or hyperglycemic events, length of hospital stay (approximately 4 days in both groups), and rates of complications (including acute respiratory failure, acute kidney injury, and myocardial infarction) between groups.
Conclusion. Inpatient treatment with sitagliptin plus glargine was noninferior to basal–bolus insulin therapy in measurements of glycemic control.
Commentary
Approximately 25% to 30% of adult patients admitted to general medical and surgical wards and critical care units have type 2 diabetes [1]. Maintaining adequate blood sugar control is important, as both hyperglycemia and hypoglycemia have been associated with adverse outcomes. Although group consensus statements differ slightly with respect to recommended target glucose levels, generally the recommended range in a noncritical inpatient setting is 140 to 180 mg/dL [2,3]. Establishing and maintaining these levels can often be very challenging. Barriers to achieving adequate glucose control in the inpatient setting include changes in a patients’ nutrition status, renal function, pain level, the use of glucocorticoids, and the development of infections. In addition, a significant gap in knowledge can exist from provider to provider in terms of how to appropriately initiate and titrate insulin regimens. To circumvent this, many hospitals have created built-in order sets and protocols in the electronic medical record for basal–bolus correction insulin regimens. While these protocols may have improved many parameters of inpatient diabetes management at several institutions, improper initiation and execution of these protocols still occur. Also, at times the priorities of the medical team can shift so that titration of the insulin regimen may not occur frequently enough. Overall, simplification of inpatient glucose management would certainly be a welcomed change.
Unfortunately, there is a dearth of studies that investigate the role of oral therapy in the inpatient setting. In general, oral medications are discontinued upon admission and insulin is the recommended standard of care. In this study, Pasquel and colleagues investigated the use of the DPP-4 inhibitor sitagliptin in the inpatient setting. Unlike some of the other classes of oral agents used in the outpatient setting, DPP-4 inhibitors are generally well tolerated. A major advantage of DPP-4 inhibitors is that, with dose titration, they can also be used in mild to moderate renal failure. However, because DPP-4 inhibitors work in the prandial setting, they are not effective in the NPO patient. In this study, both the SPG group and BBI group had similar average daily blood glucose levels after the first day of therapy and throughout the hospitalization (171 mg/dL in SPG versus 169 mg/dL in BBI). Since the key finding here was noninferiority for blood sugar control between the treatments, the major differences between SPG and BBI therapy should be highlighted.
One benefit of SPG versus BBI therapy is that replacement of bolus insulin injections with a once-daily pill reduces the need for frequent bolus insulin dose titration. Nonetheless, renal function should be monitored frequently, as sitagliptin dose adjustments may be required, and the importance of bedside glucose checks should not be diminished, as some patients may not maintain adequate control on this regimen and will need to betransitioned to BBI therapy. Both treatment groups received correctional insulin doses in the prandial setting if their pre-meal glucose levels met a specific threshold. Overall, the SPG group required significantly fewer total insulin injections per day (2.2 injections in SPG versus 2.9 injections in BBI, P < 0.001). Though this difference is rather small, the need to administer fewer insulin injections would certainly be beneficial to nursing staff, who often care for several type 2 diabetes patients at once. It would have been interesting to know how many patients in each group were free of any correctional insulin doses or how many were adequately controlled with just 1 prandial injection per day. Although it cannot be concluded from this study, it could be expected that the reduced need for bolus insulin dose titration and fewer total insulin injections associated with oral therapy would result in less insulin dosing error and perhaps greater patient satisfaction.
It is important to keep in mind that initiating a DPP-4 inhibitor with basal insulin may not be an appropriate option for all admitted type 2 diabetes patients. It can be a beneficial alternative to insulin for the select group of patients included in this study: those treated at home with diet alone, oral therapy alone, or oral therapy plus insulin.
While the potential for implementation of SPG therapy in an inpatient setting does exist, there are some limitations to this study that make further investigation necessary. Though the patent on Januvia (sitagliptin’s trade name) expires in 2017, sitagliptin is currently a very expensive drug. Therefore, a cost-benefit analysis of SPG therapy versus insulin therapy alone should be undertaken. Also, this was an unblinded study, which may have resulted in more attentive, prioritized blood sugar management than what would typically occur in an inpatient setting. Also, the providers’ level of expertise on insulin management in this study may not be generalized to all inpatient medical and surgical providers. Despite these limitations, this study may have a profound impact on inpatient diabetes management, since a less labor-intensive alternative to basal–bolus insulin therapy may present a more attractive option for many inpatient providers.
Applications for Clinical Practice
This study could pave the way for a practice-changing method of inpatient glucose management for a select group of patients who do not have severely uncontrolled type 2 diabetes. One should keep in mind that cost could be a barrier to implementation of sitagliptin in hospitals, and that while the bolus dose of insulin can be replaced with sitagliptin, patients may still need correctional doses of insulin to maintain target ranges. Also, a daily assess-ment of glucose control is still necessary in order to determine if a change in management is needed. Therefore, the sitagliptin plus glargine option should not be viewed as a “shortcut” therapy, but rather as a potentially less labor-intensive option that may increase the ability to prioritize blood sugar management in the inpatient setting.
— Lisa Parikh, MD, Yale School of Medicine,
New Haven, CT
1. Draznin B, Gilden J, Golden SH, Inzucchi SE. Pathways to quality inpatient management of hyperglycemia and diabetes: a call to action. Diabetes Care 2013;36:1807–14.
2. American Diabetes Association Standards of Medical Care in Diabetes 2017. Diabetes Care 2017;40(supplement 1).
3. Umpierrez GE, Hellman R, Korytkowski MT. Management of hyperglycemia in hospitalized patients in non-critical care setting: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012;97:16–38.
Study Overview
Objective. To compare the safety and efficacy of basal–bolus insulin therapy with sitagliptin plus insulin glargine in type 2 diabetes patients admitted to general medicine and surgical wards.
Design. Multicenter, prospective, open-label, noninferiority randomized clinical trial.
Setting and participants. Type 2 diabetes patients aged 18 to 80 years admitted to the general medicine and surgery services at one of 5 academic-based US hospitals were recruited. Eligible participants presented with a random blood glucose concentration between 140 and 400 mg/dL and were treated at home with diet, oral agents, or oral agents plus insulin at a maximum daily dose of 0.6 units/kg. Among those excluded were patients recently treated with a dipeptidyl peptidase-4 (DPP-4) inhibitor or glucagon-like peptide-1 (GLP-1) agonist, patients with clinically relevant hepatic disease, patients who were not eating for more than 48 hours, and those with an estimated glomerular filtration rate (eGFR) < 30 mL/min.
Intervention. Participants were randomly assigned to receive basal–bolus insulin therapy (BBI) with glargine once daily plus rapid-acting insulin before meals or sitagliptin plus glargine (SPG) once daily. Those in the SPG group received sitagliptin 100 mg/day if their eGFR was > 50 mL/min and sitagliptin 50 mg/day if their eGFR was 30 to 50 mL/min. If the eGFR fell below 30 mL/min during the hospitalization, sitagliptin was reduced to 25 mg/day. Glargine doses for those in the SPG group were started at 0.2 units/kg if randomization blood glucose was 140–200 mg/dL and 0.25 units/kg if randomization glucose was 201–400 mg/dL. Patients aged 70 or older or with an eGFR < 50 mL/min started with a daily glargine dose of 0.15 units/kg. For the BBI group, a total daily insulin dose of 0.4 units/kg was initiated for those with blood glucose levels between 140 and 200 mg/dL, and 0.5 units/kg for those with randomization glucose between 201 and 400 mg/dL. Half of this daily dose was given as glargine and the other half was distributed evenly across 3 pre-meal doses. Both the BBI and SPG groups received pre-meal and bedtime correction doses of rapid-acting insulin for glucose levels above 140 mg/dL. Blood glucose concentrations were measured fasting, before meals, and at bedtime or every 6 hours for patients who were not eating. Target fasting and pre-meal blood glucose levels were 100 to 140 mg/dL. Investigators and participants were not blinded to group assignment and glucose control was managed by the primary medical or surgical team.
Main outcomes measure. The primary outcome for this trial was noninferiority for differences between the SPG and BBI groups in glycemic control. Secondary endpoints included differences in the number of hypoglycemic and hyperglycemic events, the number of blood glucose values between 70 and 140 mg/dL and between 70 and 180 mg/dL, and the number of treatment failures (defined as 2 consecutive blood glucose values > 240 mg/dL or mean daily glucose > 240 mg/dL), length of hospital stay, total daily dose of insulin, number of insulin injections per day, transfer to the intensive care unit, and hospital complications and mortality.
Main results. A total of 138 patients in the SPG group and 139 patients in the BBI group completed the study and were included in this analysis. Of these 277 patients, 84% were admitted to a medicine ward and 16% were admitted to a surgical ward. The average age of participants was approximately 57 years, the average BMI was approximately 35 kg/m2, and the average duration of diabetes was approximately 10 years. These baseline characteristics as well as ethnic origin, sex, and baseline A1c (approximately 40% of patients in both groups had a baseline A1c between 7% and 9%) did not differ between groups. Prior to admission, approximately 40% of patients in both groups were managed with oral drugs alone, approximately 25% were managed with insulin alone, and about 22% were managed with insulin and oral therapy.
With respect to the primary outcome, both groups had similar mean daily blood glucose concentrations (171 mg/dL in SPG and 169 mg/dL in BBI) throughout the hospitalization, meeting the noninferiority threshold for glycemic control between groups. As for secondary outcomes, the mean proportion of blood glucose readings between 70 and 140 mg/dL, 70 and 180 mg/dL, and 100 and 140 mg/dL did not differ between groups. Pre-meal and bedtime blood glucose concentrations were also similar in both groups. There was a significant difference between groups in average daily insulin dose (24 units in SPG versus 34 units in BBI), total units of insulin per kg per day (0.2 units/kg in SPG versus 0.3 units/kg in BBI), and number of insulin injections per day (2.2 in SPG versus 2.9 in BBI). There was no difference in the number of hypoglycemic or hyperglycemic events, length of hospital stay (approximately 4 days in both groups), and rates of complications (including acute respiratory failure, acute kidney injury, and myocardial infarction) between groups.
Conclusion. Inpatient treatment with sitagliptin plus glargine was noninferior to basal–bolus insulin therapy in measurements of glycemic control.
Commentary
Approximately 25% to 30% of adult patients admitted to general medical and surgical wards and critical care units have type 2 diabetes [1]. Maintaining adequate blood sugar control is important, as both hyperglycemia and hypoglycemia have been associated with adverse outcomes. Although group consensus statements differ slightly with respect to recommended target glucose levels, generally the recommended range in a noncritical inpatient setting is 140 to 180 mg/dL [2,3]. Establishing and maintaining these levels can often be very challenging. Barriers to achieving adequate glucose control in the inpatient setting include changes in a patients’ nutrition status, renal function, pain level, the use of glucocorticoids, and the development of infections. In addition, a significant gap in knowledge can exist from provider to provider in terms of how to appropriately initiate and titrate insulin regimens. To circumvent this, many hospitals have created built-in order sets and protocols in the electronic medical record for basal–bolus correction insulin regimens. While these protocols may have improved many parameters of inpatient diabetes management at several institutions, improper initiation and execution of these protocols still occur. Also, at times the priorities of the medical team can shift so that titration of the insulin regimen may not occur frequently enough. Overall, simplification of inpatient glucose management would certainly be a welcomed change.
Unfortunately, there is a dearth of studies that investigate the role of oral therapy in the inpatient setting. In general, oral medications are discontinued upon admission and insulin is the recommended standard of care. In this study, Pasquel and colleagues investigated the use of the DPP-4 inhibitor sitagliptin in the inpatient setting. Unlike some of the other classes of oral agents used in the outpatient setting, DPP-4 inhibitors are generally well tolerated. A major advantage of DPP-4 inhibitors is that, with dose titration, they can also be used in mild to moderate renal failure. However, because DPP-4 inhibitors work in the prandial setting, they are not effective in the NPO patient. In this study, both the SPG group and BBI group had similar average daily blood glucose levels after the first day of therapy and throughout the hospitalization (171 mg/dL in SPG versus 169 mg/dL in BBI). Since the key finding here was noninferiority for blood sugar control between the treatments, the major differences between SPG and BBI therapy should be highlighted.
One benefit of SPG versus BBI therapy is that replacement of bolus insulin injections with a once-daily pill reduces the need for frequent bolus insulin dose titration. Nonetheless, renal function should be monitored frequently, as sitagliptin dose adjustments may be required, and the importance of bedside glucose checks should not be diminished, as some patients may not maintain adequate control on this regimen and will need to betransitioned to BBI therapy. Both treatment groups received correctional insulin doses in the prandial setting if their pre-meal glucose levels met a specific threshold. Overall, the SPG group required significantly fewer total insulin injections per day (2.2 injections in SPG versus 2.9 injections in BBI, P < 0.001). Though this difference is rather small, the need to administer fewer insulin injections would certainly be beneficial to nursing staff, who often care for several type 2 diabetes patients at once. It would have been interesting to know how many patients in each group were free of any correctional insulin doses or how many were adequately controlled with just 1 prandial injection per day. Although it cannot be concluded from this study, it could be expected that the reduced need for bolus insulin dose titration and fewer total insulin injections associated with oral therapy would result in less insulin dosing error and perhaps greater patient satisfaction.
It is important to keep in mind that initiating a DPP-4 inhibitor with basal insulin may not be an appropriate option for all admitted type 2 diabetes patients. It can be a beneficial alternative to insulin for the select group of patients included in this study: those treated at home with diet alone, oral therapy alone, or oral therapy plus insulin.
While the potential for implementation of SPG therapy in an inpatient setting does exist, there are some limitations to this study that make further investigation necessary. Though the patent on Januvia (sitagliptin’s trade name) expires in 2017, sitagliptin is currently a very expensive drug. Therefore, a cost-benefit analysis of SPG therapy versus insulin therapy alone should be undertaken. Also, this was an unblinded study, which may have resulted in more attentive, prioritized blood sugar management than what would typically occur in an inpatient setting. Also, the providers’ level of expertise on insulin management in this study may not be generalized to all inpatient medical and surgical providers. Despite these limitations, this study may have a profound impact on inpatient diabetes management, since a less labor-intensive alternative to basal–bolus insulin therapy may present a more attractive option for many inpatient providers.
Applications for Clinical Practice
This study could pave the way for a practice-changing method of inpatient glucose management for a select group of patients who do not have severely uncontrolled type 2 diabetes. One should keep in mind that cost could be a barrier to implementation of sitagliptin in hospitals, and that while the bolus dose of insulin can be replaced with sitagliptin, patients may still need correctional doses of insulin to maintain target ranges. Also, a daily assess-ment of glucose control is still necessary in order to determine if a change in management is needed. Therefore, the sitagliptin plus glargine option should not be viewed as a “shortcut” therapy, but rather as a potentially less labor-intensive option that may increase the ability to prioritize blood sugar management in the inpatient setting.
— Lisa Parikh, MD, Yale School of Medicine,
New Haven, CT
Study Overview
Objective. To compare the safety and efficacy of basal–bolus insulin therapy with sitagliptin plus insulin glargine in type 2 diabetes patients admitted to general medicine and surgical wards.
Design. Multicenter, prospective, open-label, noninferiority randomized clinical trial.
Setting and participants. Type 2 diabetes patients aged 18 to 80 years admitted to the general medicine and surgery services at one of 5 academic-based US hospitals were recruited. Eligible participants presented with a random blood glucose concentration between 140 and 400 mg/dL and were treated at home with diet, oral agents, or oral agents plus insulin at a maximum daily dose of 0.6 units/kg. Among those excluded were patients recently treated with a dipeptidyl peptidase-4 (DPP-4) inhibitor or glucagon-like peptide-1 (GLP-1) agonist, patients with clinically relevant hepatic disease, patients who were not eating for more than 48 hours, and those with an estimated glomerular filtration rate (eGFR) < 30 mL/min.
Intervention. Participants were randomly assigned to receive basal–bolus insulin therapy (BBI) with glargine once daily plus rapid-acting insulin before meals or sitagliptin plus glargine (SPG) once daily. Those in the SPG group received sitagliptin 100 mg/day if their eGFR was > 50 mL/min and sitagliptin 50 mg/day if their eGFR was 30 to 50 mL/min. If the eGFR fell below 30 mL/min during the hospitalization, sitagliptin was reduced to 25 mg/day. Glargine doses for those in the SPG group were started at 0.2 units/kg if randomization blood glucose was 140–200 mg/dL and 0.25 units/kg if randomization glucose was 201–400 mg/dL. Patients aged 70 or older or with an eGFR < 50 mL/min started with a daily glargine dose of 0.15 units/kg. For the BBI group, a total daily insulin dose of 0.4 units/kg was initiated for those with blood glucose levels between 140 and 200 mg/dL, and 0.5 units/kg for those with randomization glucose between 201 and 400 mg/dL. Half of this daily dose was given as glargine and the other half was distributed evenly across 3 pre-meal doses. Both the BBI and SPG groups received pre-meal and bedtime correction doses of rapid-acting insulin for glucose levels above 140 mg/dL. Blood glucose concentrations were measured fasting, before meals, and at bedtime or every 6 hours for patients who were not eating. Target fasting and pre-meal blood glucose levels were 100 to 140 mg/dL. Investigators and participants were not blinded to group assignment and glucose control was managed by the primary medical or surgical team.
Main outcomes measure. The primary outcome for this trial was noninferiority for differences between the SPG and BBI groups in glycemic control. Secondary endpoints included differences in the number of hypoglycemic and hyperglycemic events, the number of blood glucose values between 70 and 140 mg/dL and between 70 and 180 mg/dL, and the number of treatment failures (defined as 2 consecutive blood glucose values > 240 mg/dL or mean daily glucose > 240 mg/dL), length of hospital stay, total daily dose of insulin, number of insulin injections per day, transfer to the intensive care unit, and hospital complications and mortality.
Main results. A total of 138 patients in the SPG group and 139 patients in the BBI group completed the study and were included in this analysis. Of these 277 patients, 84% were admitted to a medicine ward and 16% were admitted to a surgical ward. The average age of participants was approximately 57 years, the average BMI was approximately 35 kg/m2, and the average duration of diabetes was approximately 10 years. These baseline characteristics as well as ethnic origin, sex, and baseline A1c (approximately 40% of patients in both groups had a baseline A1c between 7% and 9%) did not differ between groups. Prior to admission, approximately 40% of patients in both groups were managed with oral drugs alone, approximately 25% were managed with insulin alone, and about 22% were managed with insulin and oral therapy.
With respect to the primary outcome, both groups had similar mean daily blood glucose concentrations (171 mg/dL in SPG and 169 mg/dL in BBI) throughout the hospitalization, meeting the noninferiority threshold for glycemic control between groups. As for secondary outcomes, the mean proportion of blood glucose readings between 70 and 140 mg/dL, 70 and 180 mg/dL, and 100 and 140 mg/dL did not differ between groups. Pre-meal and bedtime blood glucose concentrations were also similar in both groups. There was a significant difference between groups in average daily insulin dose (24 units in SPG versus 34 units in BBI), total units of insulin per kg per day (0.2 units/kg in SPG versus 0.3 units/kg in BBI), and number of insulin injections per day (2.2 in SPG versus 2.9 in BBI). There was no difference in the number of hypoglycemic or hyperglycemic events, length of hospital stay (approximately 4 days in both groups), and rates of complications (including acute respiratory failure, acute kidney injury, and myocardial infarction) between groups.
Conclusion. Inpatient treatment with sitagliptin plus glargine was noninferior to basal–bolus insulin therapy in measurements of glycemic control.
Commentary
Approximately 25% to 30% of adult patients admitted to general medical and surgical wards and critical care units have type 2 diabetes [1]. Maintaining adequate blood sugar control is important, as both hyperglycemia and hypoglycemia have been associated with adverse outcomes. Although group consensus statements differ slightly with respect to recommended target glucose levels, generally the recommended range in a noncritical inpatient setting is 140 to 180 mg/dL [2,3]. Establishing and maintaining these levels can often be very challenging. Barriers to achieving adequate glucose control in the inpatient setting include changes in a patients’ nutrition status, renal function, pain level, the use of glucocorticoids, and the development of infections. In addition, a significant gap in knowledge can exist from provider to provider in terms of how to appropriately initiate and titrate insulin regimens. To circumvent this, many hospitals have created built-in order sets and protocols in the electronic medical record for basal–bolus correction insulin regimens. While these protocols may have improved many parameters of inpatient diabetes management at several institutions, improper initiation and execution of these protocols still occur. Also, at times the priorities of the medical team can shift so that titration of the insulin regimen may not occur frequently enough. Overall, simplification of inpatient glucose management would certainly be a welcomed change.
Unfortunately, there is a dearth of studies that investigate the role of oral therapy in the inpatient setting. In general, oral medications are discontinued upon admission and insulin is the recommended standard of care. In this study, Pasquel and colleagues investigated the use of the DPP-4 inhibitor sitagliptin in the inpatient setting. Unlike some of the other classes of oral agents used in the outpatient setting, DPP-4 inhibitors are generally well tolerated. A major advantage of DPP-4 inhibitors is that, with dose titration, they can also be used in mild to moderate renal failure. However, because DPP-4 inhibitors work in the prandial setting, they are not effective in the NPO patient. In this study, both the SPG group and BBI group had similar average daily blood glucose levels after the first day of therapy and throughout the hospitalization (171 mg/dL in SPG versus 169 mg/dL in BBI). Since the key finding here was noninferiority for blood sugar control between the treatments, the major differences between SPG and BBI therapy should be highlighted.
One benefit of SPG versus BBI therapy is that replacement of bolus insulin injections with a once-daily pill reduces the need for frequent bolus insulin dose titration. Nonetheless, renal function should be monitored frequently, as sitagliptin dose adjustments may be required, and the importance of bedside glucose checks should not be diminished, as some patients may not maintain adequate control on this regimen and will need to betransitioned to BBI therapy. Both treatment groups received correctional insulin doses in the prandial setting if their pre-meal glucose levels met a specific threshold. Overall, the SPG group required significantly fewer total insulin injections per day (2.2 injections in SPG versus 2.9 injections in BBI, P < 0.001). Though this difference is rather small, the need to administer fewer insulin injections would certainly be beneficial to nursing staff, who often care for several type 2 diabetes patients at once. It would have been interesting to know how many patients in each group were free of any correctional insulin doses or how many were adequately controlled with just 1 prandial injection per day. Although it cannot be concluded from this study, it could be expected that the reduced need for bolus insulin dose titration and fewer total insulin injections associated with oral therapy would result in less insulin dosing error and perhaps greater patient satisfaction.
It is important to keep in mind that initiating a DPP-4 inhibitor with basal insulin may not be an appropriate option for all admitted type 2 diabetes patients. It can be a beneficial alternative to insulin for the select group of patients included in this study: those treated at home with diet alone, oral therapy alone, or oral therapy plus insulin.
While the potential for implementation of SPG therapy in an inpatient setting does exist, there are some limitations to this study that make further investigation necessary. Though the patent on Januvia (sitagliptin’s trade name) expires in 2017, sitagliptin is currently a very expensive drug. Therefore, a cost-benefit analysis of SPG therapy versus insulin therapy alone should be undertaken. Also, this was an unblinded study, which may have resulted in more attentive, prioritized blood sugar management than what would typically occur in an inpatient setting. Also, the providers’ level of expertise on insulin management in this study may not be generalized to all inpatient medical and surgical providers. Despite these limitations, this study may have a profound impact on inpatient diabetes management, since a less labor-intensive alternative to basal–bolus insulin therapy may present a more attractive option for many inpatient providers.
Applications for Clinical Practice
This study could pave the way for a practice-changing method of inpatient glucose management for a select group of patients who do not have severely uncontrolled type 2 diabetes. One should keep in mind that cost could be a barrier to implementation of sitagliptin in hospitals, and that while the bolus dose of insulin can be replaced with sitagliptin, patients may still need correctional doses of insulin to maintain target ranges. Also, a daily assess-ment of glucose control is still necessary in order to determine if a change in management is needed. Therefore, the sitagliptin plus glargine option should not be viewed as a “shortcut” therapy, but rather as a potentially less labor-intensive option that may increase the ability to prioritize blood sugar management in the inpatient setting.
— Lisa Parikh, MD, Yale School of Medicine,
New Haven, CT
1. Draznin B, Gilden J, Golden SH, Inzucchi SE. Pathways to quality inpatient management of hyperglycemia and diabetes: a call to action. Diabetes Care 2013;36:1807–14.
2. American Diabetes Association Standards of Medical Care in Diabetes 2017. Diabetes Care 2017;40(supplement 1).
3. Umpierrez GE, Hellman R, Korytkowski MT. Management of hyperglycemia in hospitalized patients in non-critical care setting: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012;97:16–38.
1. Draznin B, Gilden J, Golden SH, Inzucchi SE. Pathways to quality inpatient management of hyperglycemia and diabetes: a call to action. Diabetes Care 2013;36:1807–14.
2. American Diabetes Association Standards of Medical Care in Diabetes 2017. Diabetes Care 2017;40(supplement 1).
3. Umpierrez GE, Hellman R, Korytkowski MT. Management of hyperglycemia in hospitalized patients in non-critical care setting: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012;97:16–38.