Efficacy of a Smart Insulin Pen Cap for the Management of Patients with Uncontrolled Type 2 Diabetes: A Randomized Cross-Over Trial.

BACKGROUND: We studied a smart insulin pen cap that can be plugged to several brand of insulin pens, to track insulin administration via smart-phone Bluetooth technology, with alarm/reminder system aiming. METHODS: This pilot randomized, cross-over design study assessed the use of a smart insulin pen cap in improving adherence, glycemic control and patient satisfaction in insulin-treated patients with poorly controlled type 2 diabetes. Eighty patients on basal insulin ± oral agents with hemoglobin A1C (HbA1c) between 7.0% and 12.0% were randomized to a 12-week active phase receiving alarms/reminders and a 12-week control/masked phase without feedback. We assessed differences between groups on treatment adherence, insulin omission, and mistiming of insulin injections, HbA1c, treatment satisfaction (using Diabetes Treatment Satisfaction Questionnaire Status). RESULTS: Compared to the control/masked phase, the active phase resulted in lower mean daily blood glucose (147.0 ± 34 vs 157.6 ± 42 mg/dL, P < .01); and greater reduction in HbA1c from baseline (-0.98% vs -0.72%, P = .006); however, no significant differences in treatment adherence, insulin omission or insulin mistiming were observed. High patient satisfaction scores were reported in both active and control phases, with DTSQc of 15.5 ± 3.7 and 14.9 ± 3.6, respectively. Statistical models showed no residual effect after cross-over between active and control phases. CONCLUSIONS: The results of this pilot study indicates that this smart insulin pen cap was effective in improving glycemic control with overall good satisfaction in insulin treated patients with type 2 diabetes. Future studies are needed to confirm its potential for improving care in insulin treated patients with diabetes.

Continuous Glucose Monitoring-Guided Insulin Administration in Hospitalized Patients With Diabetes: A Randomized Clinical Trial.

OBJECTIVE: The efficacy and safety of continuous glucose monitoring (CGM) in adjusting inpatient insulin therapy have not been evaluated. RESEARCH DESIGN AND METHODS: This randomized trial included 185 general medicine and surgery patients with type 1 and type 2 diabetes treated with a basal-bolus insulin regimen. All subjects underwent point-of-care (POC) capillary glucose testing before meals and bedtime. Patients in the standard of care (POC group) wore a blinded Dexcom G6 CGM with insulin dose adjusted based on POC results, while in the CGM group, insulin adjustment was based on daily CGM profile. Primary end points were differences in time in range (TIR; 70-180 mg/dL) and hypoglycemia (<70 mg/dL and <54 mg/dL). RESULTS: There were no significant differences in TIR (54.51% ± 27.72 vs. 48.64% ± 24.25; P = 0.14), mean daily glucose (183.2 ± 40 vs. 186.8 ± 39 mg/dL; P = 0.36), or percent of patients with CGM values <70 mg/dL (36% vs. 39%; P = 0.68) or <54 mg/dL (14 vs. 24%; P = 0.12) between the CGM-guided and POC groups. Among patients with one or more hypoglycemic events, compared with POC, the CGM group experienced a significant reduction in hypoglycemia reoccurrence (1.80 ± 1.54 vs. 2.94 ± 2.76 events/patient; P = 0.03), lower percentage of time below range <70 mg/dL (1.89% ± 3.27 vs. 5.47% ± 8.49; P = 0.02), and lower incidence rate ratio <70 mg/dL (0.53 [95% CI 0.31-0.92]) and <54 mg/dL (0.37 [95% CI 0.17-0.83]). CONCLUSIONS: The inpatient use of real-time Dexcom G6 CGM is safe and effective in guiding insulin therapy, resulting in a similar improvement in glycemic control and a significant reduction of recurrent hypoglycemic events compared with POC-guided insulin adjustment.

Efficacy and Safety of Intensive Versus Nonintensive Supplemental Insulin With a Basal-Bolus Insulin Regimen in Hospitalized Patients With Type 2 Diabetes: A Randomized Clinical Study.

OBJECTIVE: Administration of supplemental sliding scale insulin for correction of hyperglycemia in non-intensive care unit (ICU) patients with type 2 diabetes is frequently used with basal-bolus insulin regimens. In this noninferiority randomized controlled trial we tested whether glycemic control is similar with and without aggressive sliding scale insulin treatment before meals and bedtime in patients treated with basal-bolus insulin regimens. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes with admission blood glucose (BG) 140-400 mg/dL treated with basal-bolus insulin were randomized to intensive (correction for BG >140 mg/dL, n = 108) or to nonintensive (correction for BG >260 mg/dL, n = 107) administration of rapid-acting sliding scale insulin before meals and bedtime. The groups received the same amount of sliding scale insulin for BG >260 mg/dL. Primary outcome was difference in mean daily BG levels between the groups during hospitalization. RESULTS: Mean daily BG in the nonintensive group was noninferior to BG in the intensive group with equivalence margin of 18 mg/dL (intensive 172 ± 38 mg/dL vs. nonintensive 173 ± 43 mg/dL, P = 0.001 for noninferiority). There were no differences in the proportion of target BG readings of 70-180 mg/dL, <70 or <54 mg/dL (hypoglycemia), or >350 mg/dL (severe hyperglycemia) or total, basal, or prandial insulin doses. Significantly fewer subjects received sliding scale insulin in the nonintensive (n = 36 [34%]) compared with the intensive (n = 98 [91%] [P < 0.0001]) group with no differences in sliding scale insulin doses between the groups among those who received sliding scale insulin (intensive 7 ± 4 units/day vs. nonintensive 8 ± 4 units/day, P = 0.34). CONCLUSIONS: Among non-ICU patients with type 2 diabetes on optimal basal-bolus insulin regimen with moderate hyperglycemia (BG <260 mg/dL), a less intensive sliding scale insulin treatment did not significantly affect glycemic control.

Degludec hospital trial: A randomized controlled trial comparing insulin degludec U100 and glargine U100 for the inpatient management of patients with type 2 diabetes.

AIMS: Limited data exist about the use of insulin degludec in the hospital. This multicentre, non-inferiority, open-label, prospective randomized trial compared the safety and efficacy of insulin degludec-U100 and glargine-U100 for the management of hospitalized patients with type 2 diabetes. METHODS: In total, 180 general medical and surgical patients with an admission blood glucose (BG) between 7.8 and 22.2 mmol/L, treated with oral agents or insulin before hospitalization were randomly allocated (1:1) to a basal-bolus regimen using degludec (n = 92) or glargine (n = 88), as basal and aspart before meals. Insulin dose was adjusted daily to a target BG between 3.9 and 10.0 mmol/L. The primary endpoint was the difference in mean hospital daily BG between groups. RESULTS: Overall, the randomization BG was 12.2 ± 2.9 mmol/L and glycated haemoglobin 84 mmol/mol (9.8% ± 2.0%). There were no differences in mean daily BG (10.0 ± 2.1 vs. 10.0 ± 2.5 mmol/L, p = .9), proportion of BG in target range (54·5% ± 29% vs. 55·3% ± 28%, p = .85), basal insulin (29.6 ± 13 vs. 30.4 ± 18 units/day, p = .85), length of stay [median (IQR): 6.7 (4.7-10.5) vs. 7.5 (4.7-11.6) days, p = .61], hospital complications (23% vs. 23%, p = .95) between treatment groups. There were no differences in the proportion of patients with BG <3.9 mmol/L (17% vs. 19%, p = .75) or <3.0 mmol/L (3.7% vs. 1.3%, p = .62) between degludec and glargine. CONCLUSION: Hospital treatment with degludec-U100 or glargine-U100 is equally safe and effective for the management of hyperglycaemia in general medical and surgical patients with type 2 diabetes.

Accuracy of Dexcom G6 Continuous Glucose Monitoring in Non-Critically Ill Hospitalized Patients With Diabetes.

OBJECTIVE: Advances in continuous glucose monitoring (CGM) have transformed ambulatory diabetes management. Until recently, inpatient use of CGM has remained investigational, with limited data on its accuracy in the hospital setting. RESEARCH DESIGN AND METHODS: To analyze the accuracy of Dexcom G6, we compared retrospective matched-pair CGM and capillary point-of-care (POC) glucose data from three inpatient CGM studies (two interventional and one observational) in general medicine and surgery patients with diabetes treated with insulin. Analysis of accuracy metrics included mean absolute relative difference (MARD), median absolute relative difference (ARD), and proportion of CGM values within 15, 20, and 30% or 15, 20, and 30 mg/dL of POC reference values for blood glucose >100 mg/dL or ≤100 mg/dL, respectively (% 15/15, % 20/20, % 30/30). Clinical reliability was assessed with Clarke error grid (CEG) analyses. RESULTS: A total of 218 patients were included (96% with type 2 diabetes) with a mean age of 60.6 ± 12 years. The overall MARD (n = 4,067 matched glucose pairs) was 12.8%, and median ARD was 10.1% (interquartile range 4.6, 17.6]. The proportions of readings meeting % 15/15, % 20/20, and % 30/30 criteria were 68.7, 81.7, and 93.8%, respectively. CEG analysis showed 98.7% of all values in zones A and B. MARD and median ARD were higher in the case of hypoglycemia (<70 mg/dL) and severe anemia (hemoglobin <7 g/dL). CONCLUSIONS: Our results indicate that CGM technology is a reliable tool for hospital use and may help improve glucose monitoring in non-critically ill hospitalized patients with diabetes.

Liraglutide hospital discharge trial: A randomized controlled trial comparing the safety and efficacy of liraglutide versus insulin glargine for the management of patients with type 2 diabetes after hospital discharge.

AIM: To compare a glucagon-like peptide-1 receptor agonist with basal insulin at hospital discharge in patients with uncontrolled type 2 diabetes in a randomized clinical trial. METHODS: A total of 273 patients with glycated haemoglobin (HbA1c) 7%-10% (53-86 mol/mol) were randomized to liraglutide (n = 136) or insulin glargine (n = 137) at hospital discharge. The primary endpoint was difference in HbA1c at 12 and 26 weeks. Secondary endpoints included hypoglycaemia, changes in body weight, and achievement of HbA1c <7% (53 mmol/mol) without hypoglycaemia or weight gain. RESULTS: The between-group difference in HbA1c at 12 weeks and 26 weeks was -0.28% (95% CI -0.64, 0.09), and at 26 weeks it was -0.55%, (95% CI -1.01, -0.09) in favour of liraglutide. Liraglutide treatment resulted in a lower frequency of hypoglycaemia <3.9 mmol/L (13% vs 23%; P = 0.04), but there was no difference in the rate of clinically significant hypoglycaemia <3.0 mmol/L. Compared to insulin glargine, liraglutide treatment was associated with greater weight loss at 26 weeks (-4.7 ± 7.7 kg vs -0.6 ± 11.5 kg; P < 0.001), and the proportion of patients with HbA1c <7% (53 mmol/mol) without hypoglycaemia was 48% versus 33% (P = 0.05) at 12 weeks and 45% versus 33% (P = 0.14) at 26 weeks in liraglutide versus insulin glargine. The proportion of patients with HbA1c <7% (53 mmol/mol) without hypoglycaemia and no weight gain was higher with liraglutide at 12 (41% vs 24%, P = 0.005) and 26 weeks (39% vs 22%; P = 0.014). The incidence of gastrointestinal adverse events was higher with liraglutide than with insulin glargine (P < 0.001). CONCLUSION: Compared to insulin glargine, treatment with liraglutide at hospital discharge resulted in better glycaemic control and greater weight loss, but increased gastrointestinal adverse events.

Sitagliptin for the prevention and treatment of perioperative hyperglycaemia in patients with type 2 diabetes undergoing cardiac surgery: A randomized controlled trial.

AIM: To assess whether treatment with sitagliptin, starting before surgery and continued during the hospital stay, can prevent and reduce the severity of perioperative hyperglycaemia in patients with type 2 diabetes undergoing coronary artery bypass graft (CABG) surgery. MATERIALS AND METHODS: We conducted a double-blinded, placebo-controlled trial in adults with type 2 diabetes randomly assigned to receive sitagliptin or matching placebo starting 1 day prior to surgery and continued during the hospital stay. The primary outcome was difference in the proportion of patients with postoperative hyperglycaemia (blood glucose [BG] > 10 mmol/L [>180 mg/dL]) in the intensive care unit (ICU). Secondary endpoints included differences in mean daily BG in the ICU and after transition to regular wards, hypoglycaemia, hospital complications, length of stay and need of insulin therapy. RESULTS: We included 182 participants randomized to receive sitagliptin or placebo (91 per group, age 64 ± 9 years, HbA1c 7.6% ± 1.5% and diabetes duration 10 ± 9 years). There were no differences in the number of patients with postoperative BG greater than 10 mmol/L, mean daily BG in the ICU or after transition to regular wards, hypoglycaemia, hospital complications or length of stay. There were no differences in insulin requirements in the ICU; however, sitagliptin therapy was associated with lower mean daily insulin requirements (21.1 ± 18.4 vs. 32.5 ± 26.3 units, P = .007) after transition to a regular ward compared with placebo. CONCLUSION: The administration of sitagliptin prior to surgery and during the hospital stay did not prevent perioperative hyperglycaemia or complications after CABG. Sitagliptin therapy was associated with lower mean daily insulin requirements after transition to regular wards.

A Randomized Controlled Trial Comparing Glargine U300 and Glargine U100 for the Inpatient Management of Medicine and Surgery Patients With Type 2 Diabetes: Glargine U300 Hospital Trial.

OBJECTIVE: The role of U300 glargine insulin for the inpatient management of type 2 diabetes (T2D) has not been determined. We compared the safety and efficacy of glargine U300 versus glargine U100 in noncritically ill patients with T2D. RESEARCH DESIGN AND METHODS: This prospective, open-label, randomized clinical trial included 176 patients with poorly controlled T2D (admission blood glucose [BG] 228 ± 82 mg/dL and HbA1c 9.5 ± 2.2%), treated with oral agents or insulin before admission. Patients were treated with a basal-bolus regimen with glargine U300 (n = 92) or glargine U100 (n = 84) and glulisine before meals. We adjusted insulin daily to a target BG of 70-180 mg/dL. The primary end point was noninferiority in the mean difference in daily BG between groups. The major safety outcome was the occurrence of hypoglycemia. RESULTS: There were no differences between glargine U300 and U100 in mean daily BG (186 ± 40 vs. 184 ± 46 mg/dL, P = 0.62), percentage of readings within target BG of 70-180 mg/dL (50 ± 27% vs. 55 ± 29%, P = 0.3), length of stay (median [IQR] 6.0 [4.0, 8.0] vs. 4.0 [3.0, 7.0] days, P = 0.06), hospital complications (6.5% vs. 11%, P = 0.42), or insulin total daily dose (0.43 ± 0.21 vs. 0.42 ± 0.20 units/kg/day, P = 0.74). There were no differences in the proportion of patients with BG <70 mg/dL (8.7% vs. 9.5%, P > 0.99), but glargine U300 resulted in significantly lower rates of clinically significant hypoglycemia (<54 mg/dL) compared with glargine U100 (0% vs. 6.0%, P = 0.023). CONCLUSIONS: Hospital treatment with glargine U300 resulted in similar glycemic control compared with glargine U100 and may be associated with a lower incidence of clinically significant hypoglycemia.

Clinical characteristics and outcomes of patients with end-stage renal disease hospitalized with diabetes ketoacidosis.

INTRODUCTION: There is limited evidence to guide management in patients with end-stage renal disease (ESRD) on chronic hemodialysis admitted with diabetes ketoacidosis. Thus, we investigated the clinical characteristics and outcomes of patients with ESRD admitted with diabetic ketoacidosis (DKA). METHODS: In this observational study, we used International Classification of Diseases Ninth/Tenth Revision codes to identify adult (aged 18-80 years) patients admitted to Emory University Hospitals between 1 January 2006 and 31 December 2016. DKA and ESRD diagnoses were confirmed by reviewing medical records and by admission laboratory results. RESULTS: Among 307 patients with DKA meeting the inclusion and exclusion criteria, 22.1% (n: 68) had ESRD on hemodialysis and 77.9% (n: 239) had preserved renal function (estimated glomerular filtration rate >60 mL/min/1.73 m2). Compared with patients with preserved renal function, the admission blood glucose was higher (804.5±362.6 mg/dL vs 472.5±137.7 mg/dL) and the mean hemoglobin A1c was lower (9.6%±2.1 vs 12.0%±2.5) in patients with DKA and ESRD, both p<0.001. The rates of hypoglycemia <70 mg/dL (34% vs 14%, p=0.002) and <54 mg/dL (13% vs 5%, p=0.04) were higher in the ESRD group. During hospitalization, more patients with ESRD develop volume overload (28% vs 3%, p<0.001) and require mechanical ventilation (24% vs 3%, p=<0.001). There were no differences in hospital mortality (3% vs 0%, p=0.21), but length of stay (median 7.0 vs 3.0 days, p<0.001) was longer in the ESRD cohort. After adjusting for multiple covariates, patients with DKA and ESRD have higher odds of hypoglycemia (OR 3.3, 95% CI 1.51 to 7.21, p=0.003) and volume overload (OR 4.22, 95% CI 1.37 to 13.05, p=0.01) compared with patients with DKA with preserved renal function. CONCLUSIONS: Patients with DKA and ESRD on chronic hemodialysis had worse clinical outcomes including higher rates of hypoglycemia, volume overload, need for mechanical ventilation and longer length of stay, compared with patients with preserved kidney function.

Safety And Efficacy Of Dpp-4 Inhibitors For The Management Of Hospitalized General Medicine And Surgery Patients with Type 2 Diabetes.

OBJECTIVE: DPP-4 inhibitors (DPP-4i) have been shown to be effective for the management of inpatient diabetes. We report pooled data from 3 prospective studies using DPP-4i in general medicine and surgery patients with type 2 diabetes (T2D). METHODS: We combined data from 3 randomized studies comparing DPP-4i alone or in combination with basal insulin or a basal-bolus insulin regimen. Medicine (n = 266) and surgery (n = 319) patients admitted with a blood glucose (BG) between 140 and 400 mg/dL, treated with diet, oral agents, or low-dose insulin therapy were included. Patients received DPP-4i alone (n = 144), DPP-4i plus basal insulin (n = 158) or basal-bolus regimen (n = 283). All groups received correctional doses with rapid-acting insulin for BG >140 mg/dL. The primary endpoint was differences in mean daily BG between groups. Secondary endpoints included differences in hypoglycemia and hospital complications. RESULTS: There were no differences in mean hospital daily BG among patients treated with DPP-4i alone (170 ± 37 mg/dL), DPP-4i plus basal (172 ± 42 mg/dL), or basalbolus (172 ± 43 mg/dL), P = .94; or in the percentage of BG readings within target of 70 to 180 mg/dL (63 ± 32%, 60 ± 31%, and 64 ± 28%, respectively; P = .42). There were no differences in length of stay or complications, but hypoglycemia was less common with DPP-4i alone (2%) compared to DPP-4i plus basal (9%) and basal-bolus (10%); P = .004. CONCLUSION: Treatment with DPP-4i alone or in combination with basal insulin is effective and results in a lower incidence of hypoglycemia compared to a basal-bolus insulin regimen in general medicine and surgery patients with T2D. ABBREVIATIONS: BG = blood glucose; BMI = body mass index; CI = confidence interval; DPP-4i = dipeptidyl peptidase-4 inhibitors; HbA1c = hemoglobin A1c; OR = odds ratio; T2D = type 2 diabetes.

Clinical Outcomes in Patients With Isolated or Combined Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State: A Retrospective, Hospital-Based Cohort Study.

OBJECTIVE: Many patients with hyperglycemic crises present with combined features of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). The implications of concomitant acidosis and hyperosmolality are not well known. We investigated hospital outcomes in patients with isolated or combined hyperglycemic crises. RESEARCH DESIGN AND METHODS: We analyzed admissions data listing DKA or HHS at two academic hospitals. We determined 1) the frequency distributions of HHS, DKA, and combined DKA-HHS (DKA criteria plus elevated effective osmolality); 2) the relationship of markers of severity of illness and clinical comorbidities with 30-day all-cause mortality; and 3) the relationship of hospital complications associated with insulin therapy (hypoglycemia and hypokalemia) with mortality. RESULTS: There were 1,211 patients who had a first admission with confirmed hyperglycemic crises criteria, 465 (38%) who had isolated DKA, 421 (35%) who had isolated HHS, and 325 (27%) who had combined features of DKA-HHS. After adjustment for age, sex, BMI, race, and Charlson Comorbidity Index score, subjects with combined DKA-HHS had higher in-hospital mortality compared with subjects with isolated hyperglycemic crises (adjusted odds ratio [aOR] 2.7; 95% CI 1.4, 4.9; P = 0.0019). In all groups, hypoglycemia (<40 mg/dL) during treatment was associated with a 4.8-fold increase in mortality (aOR 4.8; 95% CI 1.4, 16.8). Hypokalemia ≤3.5 mEq/L was frequent (55%). Severe hypokalemia (≤2.5 mEq/L) was associated with increased inpatient mortality (aOR 4.9; 95% CI 1.3, 18.8; P = 0.02). CONCLUSIONS: Combined DKA-HHS is associated with higher mortality compared with isolated DKA or HHS. Severe hypokalemia and severe hypoglycemia are associated with higher hospital mortality in patients with hyperglycemic crises.

Sitagliptin for the prevention of stress hyperglycemia in patients without diabetes undergoing coronary artery bypass graft (CABG) surgery.

Aims: To determine if treatment with sitagliptin, a dipeptidyl peptidase-4 inhibitor, can prevent stress hyperglycemia in patients without diabetes undergoing coronary artery bypass graft (CABG) surgery. Methods: We conducted a pilot, double-blinded, placebo-controlled randomized trial in adults (18-80 years) without history of diabetes. Participants received sitagliptin or placebo once daily, starting the day prior to surgery and continued for up to 10 days. Primary outcome was differences in the frequency of stress hyperglycemia (blood glucose (BG) >180 mg/dL) after surgery among groups. Results: We randomized 32 participants to receive sitagliptin and 28 to placebo (mean age 64±10 years and HbA1c: 5.6%±0.5%). Treatment with sitagliptin resulted in lower BG levels prior to surgery (101±mg/dL vs 107±13 mg/dL, p=0.01); however, there were no differences in the mean BG concentration, proportion of patients who developed stress hyperglycemia (21% vs 22%, p>0.99), length of hospital stay, rate of perioperative complications and need for insulin therapy in the intensive care unit or during the hospital stay. Conclusion: The use of sitagliptin during the perioperative period did not prevent the development of stress hyperglycemia or need for insulin therapy in patients without diabetes undergoing CABG surgery.

A Randomized Controlled Trial on the Safety and Efficacy of Exenatide Therapy for the Inpatient Management of General Medicine and Surgery Patients With Type 2 Diabetes.

OBJECTIVE: This multicenter, open-label, randomized trial examined the safety and efficacy of exenatide alone or in combination with basal insulin in non-critically ill patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: A total of 150 patients with blood glucose (BG) between 140 and 400 mg/dL, treated at home with diet, oral agents, or insulin at a total daily dose <0.5 units/kg, were randomized to exenatide alone (5 µg twice daily), exenatide plus basal insulin, or a basal-bolus insulin regimen. The primary end point was difference in mean daily BG concentration among groups. RESULTS: Mean daily BG was similar between patients treated with exenatide plus basal and a basal-bolus regimen (154 ± 39 vs. 166 ± 40 mg/dL, P = 0.31), and exenatide plus basal resulted in lower daily BG than did exenatide alone (177 ± 41 mg/dL, P = 0.02). Exenatide plus basal resulted in a higher proportion of BG levels in target range between 70 and 180 mg/dL compared with exenatide and basal-bolus (78% vs. 62% vs. 63%, respectively, P = 0.023). More patients in the exenatide and exenatide plus basal groups experienced nausea or vomiting than in the basal-bolus group (10% vs. 11% vs. 2%, P = 0.17), with three patients (6%) discontinued exenatide owing to adverse events. There were no differences in hypoglycemia <54 mg/dL (2% vs. 0% vs. 4%, P = 0.77) or length of stay (5 vs. 4 vs. 4 days, P = 0.23) among basal plus exenatide, exenatide, and basal-bolus groups. CONCLUSIONS: The results of this pilot study indicate that exenatide alone or in combination with basal insulin is safe and effective for the management of hospitalized general medical and surgical patients with T2D.

Glycaemic efficacy and safety of linagliptin compared to a basal-bolus insulin regimen in patients with type 2 diabetes undergoing non-cardiac surgery: A multicentre randomized clinical trial.

AIMS: The use of incretin-based therapy, rather than or complementary to, insulin therapy is an active area of research in hospitalized patients with type 2 diabetes (T2D). We determined the glycaemic efficacy and safety of linagliptin compared to a basal-bolus insulin regimen in hospitalized surgical patients with T2D. MATERIALS AND METHODS: This prospective open-label multicentre study randomized T2D patients undergoing non-cardiac surgery with admission blood glucose (BG) of 7.8 to 22.2 mmol/L who were under treatment with diet, oral agents or total insulin dose (TDD) ≤ 0.5 units/kg/day to either linagliptin (n = 128) daily or basal-bolus (n = 122) with glargine once daily and rapid-acting insulin before meals. Both groups received supplemental insulin for BG > 7.8 mmol/L. The primary endpoint was difference in mean daily BG between groups. RESULTS: Mean daily BG was higher in the linagliptin group compared to the basal-bolus group (9.5 ± 2.6 vs 8.8 ± 2.3 mmol/L/dL, P = 0.03) with a mean daily BG difference of 0.6 mmol/L (95% confidence interval 0.04, 1.2). In patients with randomization BG < 11.1 mmol/L (63% of cohort), mean daily BG was similar in the linagliptin and basal-bolus groups (8.9 ± 2.3 vs 8.7 ± 2.3 mmol/L, P = 0.43); however, patients with BG ≥ 11.1 mmol/L who were treated with linagliptin had higher BG compared to the basal-bolus group (10.9 ± 2.6 vs 9.2 ± 2.2 mmol/L, P < 0.001). Linagliptin resulted in fewer hypoglycaemic events (1.6% vs 11%, P = 0.001; 86% relative risk reduction), with similar supplemental insulin and fewer daily insulin injections (2.0 ± 3.3 vs 3.1 ± 3.3, P < 0.001) compared to the basal-bolus group. CONCLUSIONS: For patients with T2D undergoing non-cardiac surgery who presented with mild to moderate hyperglycaemia (BG < 11.1 mmol/L), daily linagliptin is a safe and effective alternative to multi-dose insulin therapy, resulting in similar glucose control with lower hypoglycaemia.

A Randomized Controlled Study Comparing a DPP4 Inhibitor (Linagliptin) and Basal Insulin (Glargine) in Patients With Type 2 Diabetes in Long-term Care and Skilled Nursing Facilities: Linagliptin-LTC Trial.

OBJECTIVES: Safe and easily implemented treatment regimens are needed for the management of patients with type 2 diabetes mellitus (T2DM) in long-term care (LTC) and skilled nursing facilities. DESIGN: This 6-month open-label randomized controlled trial compared the efficacy and safety of a DPP4 inhibitor (linagliptin) and basal insulin (glargine) in LTC residents with T2DM. SETTINGS: Three LTC institutions affiliated with a community safety-net hospital, US Department of Veterans Affairs and Emory Healthcare System in Atlanta, Georgia. PARTICIPANTS: A total of 140 residents with T2DM treated with oral antidiabetic agents or low-dose insulin (≤0.1 U/kg/d), with fasting or premeal blood glucose (BG) > 180 mg/dL and/or HbA1c >7.5%. INTERVENTION: Baseline antidiabetic therapy, except metformin, was discontinued on trial entry. Residents were treated with linagliptin 5 mg/d (n = 67) or glargine at a starting dose of 0.1 U/kg/d (n = 73). Both groups received supplemental rapid-acting insulin before meals for BG > 200 mg/dL. MEASUREMENTS: Primary outcome was mean difference in daily BG between groups. Main secondary endpoints included differences in frequency of hypoglycemia, glycosylated hemoglobin (HbA1c), complications, emergency department visits, and hospital transfers. RESULTS: Treatment with linagliptin resulted in no significant differences in mean daily BG (146 ± 34 mg/dL vs. 157 ± 36 mg/dL, P = .07) compared to glargine. Linagliptin treatment resulted in fewer mild hypoglycemic events <70 mg/dL (3% vs. 37%, P < .001), but there were no differences in BG < 54 mg/dL (P = .06) or <40 mg/dL (P = .05) compared to glargine. There were no significant between-group differences in HbA1c, length of stay, complications, emergency department visits, or hospitalizations. CONCLUSION: Treatment with linagliptin resulted in noninferior glycemic control and in significantly lower risk of hypoglycemia compared to insulin glargine in long-term care and skilled nursing facility residents with type 2 diabetes.

Clinical characteristics and outcomes of symptomatic and asymptomatic hypoglycemia in hospitalized patients with diabetes.

IMPORTANCE: The frequency and impact of asymptomatic hypoglycemia in hospitalized patients with diabetes is not known. OBJECTIVE: We determined the clinical characteristics and hospital outcomes of general medicine and surgery patients with symptomatic and asymptomatic hypoglycemia. RESEARCH DESIGN AND METHODS: Prospective observational study in adult patients with diabetes and blood glucose (BG) <70 mg/dL. Participants were interviewed about signs and symptoms of hypoglycemia using a standardized questionnaire. Precipitating causes, demographics, insulin regimen, and complications data during admission was collected. RESULTS: Among 250 patients with hypoglycemia, 112 (44.8%) patients were asymptomatic and 138 (55.2%) had symptomatic hypoglycemia. Patients with asymptomatic hypoglycemia were older (59±11 years vs 54.8±13 years, p=0.003), predominantly males (63% vs 48%, p=0.014), and had lower admission glycosylated hemoglobin (8.2%±2.6 % vs 9.1±2.9%, p=0.006) compared with symptomatic patients. Compared with symptomatic patients, those with asymptomatic hypoglycemia had higher mean BG during the episode (60.0±8 mg/dL vs 53.8±11 mg/dL, p<0.001). In multivariate analysis, male gender (OR 2.08, 95% CI 1.13 to 3.83, p=0.02) and age >65 years (OR 4.01, 95% CI 1.62 to 9.92, p=0.02) were independent predictors of asymptomatic hypoglycemia. There were no differences in clinical outcome, composite of hospital complications (27% vs 22%, p=0.41) or in-hospital length of stay (8 days (IQR 4-14) vs 7 days (IQR 5-15), p=0.92)) between groups. CONCLUSIONS: Asymptomatic hypoglycemia was common among insulin-treated patients with diabetes but was not associated with worse clinical outcome compared with patients with symptomatic hypoglycemia. Older age and male gender were independent risk factors for asymptomatic hypoglycemia.

Hospitalization costs and clinical outcomes in CABG patients treated with intensive insulin therapy.

BACKGROUND: The financial impact of intensive (blood glucose [BG] 100-140mg/dl [5.5-7.8mM] vs. conservative (141-180mg/dl (7.9-10.0mM) glucose control in the ICU in patients, with and without diabetes, undergoing coronary artery bypass graft (CABG) surgery is not known. METHODS: This post-hoc cost analysis determined differences in hospitalization costs, resource utilization and perioperative complications in 288 CABG patients with diabetes (n=143) and without diabetes (n=145), randomized to intensive (n=143) and conservative (n=145) glucose control. RESULTS: Intensive glucose control resulted in lower BG (131.4±14mg/dl-(7.2±0.8mM) vs. 151.6±17mg/dl (8.4±0.8mM, p<0.001), a nonsignificant reduction in the median length of stay (LOS, 7.9 vs. 8.5days, p=0.17) and in a composite of perioperative complications including wound infection, bacteremia, acute renal and respiratory failure, major cardiovascular events (42% vs 52%, p=0.10) compared to conservative control. Median hospitalization costs were lower in the intensive group ($39,366 vs. $42,141, p=0.040), with a total cost savings of $3654 (95% CI: $1780-$3723), than conservative control. Resource utilization for radiology (p=0.008), laboratory (p=0.014), consultation service (p=0.013), and ICU utilization (p=0.007) were also lower in the intensive group. Compared to patients without perioperative complications, those with complications had longer hospital length of stay (10.7days vs. 6.7days, p<0.001), higher total hospitalization cost ($48,299 vs. $32,675, p<0.001), and higher resource utilization units (2745 vs. 1710, p<0.001). CONCLUSION: Intensive glycemic control [BG 100-140mg/dl (5.5-7.8mM)] in patients undergoing CABG resulted in significant reductions in hospitalization costs and resource utilization compared to patients treated with conservative [BG 141-180mg/dl (7.9-10.0mM)] glucose control.

Inflammation and Oxidative Stress in Cardiac Surgery Patients Treated to Intensive Versus Conservative Glucose Targets.

Objective: We aimed to determine (a) longitudinal changes of inflammatory and oxidative stress markers and (b) the association between markers of inflammation and perioperative complications in coronary artery bypass surgery (CABG) patients treated with intensive vs conservative blood glucose (BG) control. Methods: Patients with diabetes (n = 152) and without diabetes with hyperglycemia (n = 150) were randomized to intensive (n = 151; BG: 100-140 mg/dL) or to conservative (n = 151; BG: 141-180 mg/dL) glycemic targets. Plasma cortisol, high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor-α, interleukin-6 (IL-6), thiobarbituric acid-reactive substances, and 2'-7'-dichlorofluorescein were measured prior to and at days 3, 5, and 30 after surgery. Results: Intensive glycemic control resulted in lower mean BG (132 ± 14 mg/dL vs 154 ± 17 mg/dL, P < 0.001) in the intensive care unit. Plasma cortisol and inflammatory markers increased significantly from baseline after the third and fifth day of surgery (P < 0.001), and returned to baseline levels at 1 month of follow-up. Patients with perioperative complications had higher levels of cortisol, hsCRP, IL-6, and oxidative stress markers compared with those without complications. There were no significant differences in inflammatory and oxidative stress markers between patients, with or without diabetes or complications, treated with intensive or conventional glucose targets. Conclusion: We report no significant differences in circulating markers of acute inflammatory and oxidative stress response in cardiac surgery patients, with or without diabetes, treated with intensive (100-140 mg/dL) or conservative (141-180 mg/dL) insulin regimens.