A Randomized Controlled Trial Comparing the Efficacy and Safety of IDegLira Versus Basal-Bolus in Patients With Poorly Controlled Type 2 Diabetes and Very High HbA1c ≥9-15%: DUAL HIGH Trial.

OBJECTIVE: In participants with type 2 diabetes (T2D) and HbA1c >9.0-10.0%, guidelines recommend treatment with basal-bolus insulin. RESEARCH DESIGN AND METHODS: This randomized trial compared the efficacy and safety of insulin degludec and liraglutide (IDegLira) and basal-bolus among participants with high HbA1c ≥9.0-15.0%, previously treated with 2 or 3 oral agents and/or basal insulin, allocated (1:1) to basal-bolus (n = 73) or IDegLira (n = 72). The primary end point was noninferiority (0.4%) in HbA1c reduction between groups. RESULTS: Among 145 participants (HbA1c 10.8% ± 1.3), there was no statistically significant difference in HbA1c reduction (3.18% ± 2.29 vs. 3.00% ± 1.79, P = 0.65; estimated treatment difference (ETD) 0.18%, 95% CI -0.59, 0.94) between the IDegLira and basal-bolus groups. IDegLira resulted in significantly lower rates of hypoglycemia <70 mg/dL (26% vs. 48%, P = 0.008; odds ratio 0.39, 95% CI 0.19, 0.78), and less weight gain (1.24 ± 8.33 vs. 5.84 ± 6.18 kg, P = 0.001; ETD -4.60, 95% CI -7.33, -1.87). CONCLUSIONS: In participants with T2D and HbA1c ≥9.0-15.0%, IDegLira resulted in similar HbA1c reduction, less hypoglycemia, and less weight gain compared with the basal-bolus regimen.

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.

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.

Biochemical Parameters of Diabetes Ketoacidosis in Patients with End-stage Kidney Disease and Preserved Renal Function.

INTRODUCTION: Differences in biochemical parameters of diabetic ketoacidosis in patients with end-stage kidney disease (ESKD) has not been established. Accordingly, we assessed the relationship between degree of metabolic acidosis and ß-hydroxybutyrate in patients with ESKD (eGFR < 15 mL/min/1.73 m2), moderate renal failure (eGFR 15-60), or preserved renal function (eGFR > 60). METHODS: This observational study included adults (18-80 years) with diabetes ketoacidosis (DKA), admitted to Emory University Hospitals between January 1, 2006 to December 31, 2016. DKA and renal stages were confirmed on admission laboratory values. RESULTS: Admission bicarbonate levels (13.9 ± 5 vs 13.4 ± 5.3 vs 13.8 ± 4.2 mmol/L, P = 0.7), and pH levels (7.2 ± 0.3 vs 7.2 ± 0.2 vs 7.2 ± 0.2, P = 0.8) were similar among groups. Patients with ESKD had lower mean ß-hydroxybutyrate level (4.3 ± 3.3 vs 5.6 ± 2.9 vs 5.9 ± 2.5 mmol/L, P = 0.01), but higher admission glucose (852 ± 340.4 vs 714.6 ± 253.3 mg/dL vs 518 ± 185.7 mg/dL, P < 0.01), anion gap (23.4 ± 7.6 vs 23 ± 6.9 vs 19.5 ± 4.7 mmol/L, P < 0.01), and osmolality (306 ± 20.6 vs 303.5 ± vs 293.1 ± 3.1mOsm/kg, P < 0.01) compared with patients with moderate renal failure and preserved renal function, respectively. The sensitivity of ß-hydroxybutyrate > 3 mmol/L for diagnosing DKA by bicarbonate level < 15 and <18 mmol/L was 86.9% and 72% in ESKD, 89.3% and 83.7% in moderate renal failure, and 96.2% and 88.3% in preserved renal function. In patients with ESKD, the corresponding ß-hydroxybutyrate with bicarbonate levels < 10, 10-15, <18 mmol/L were 5.5, 3.9, 3.0 mmol/L, respectively. CONCLUSIONS: Significant metabolic differences were found among DKA patients with different levels of renal function. In patients with ESKD, a ß-hydroxybutyrate level > 3 mmol/L may assist with confirmation of DKA diagnosis.

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.

Comparison of the FreeStyle Libre Pro Flash Continuous Glucose Monitoring (CGM) System and Point-of-Care Capillary Glucose Testing in Hospitalized Patients With Type 2 Diabetes Treated With Basal-Bolus Insulin Regimen.

OBJECTIVE: We compared the performance of the FreeStyle Libre Pro continuous glucose monitoring (CGM) and point-of-care capillary glucose testing (POC) among insulin-treated hospitalized patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: This was a prospective study in adult patients with T2D admitted to general medicine and surgery wards. Patients were monitored with POC before meals and bedtime and with CGM during the hospital stay. Study end points included differences between POC and CGM in mean daily blood glucose (BG), hypoglycemia <70 and <54 mg/dL, and nocturnal hypoglycemia. We also calculated the mean absolute relative difference (MARD), ±15%/15 mg/dL, ±20%/20 mg/dL, and ±30%/30 mg/dL and error grid analysis between matched glucose pairs. RESULTS: Mean daily glucose was significantly higher by POC (188.9 ± 37.3 vs. 176.1 ± 46.9 mg/dL) with an estimated mean difference of 12.8 mg/dL (95% CI 8.3-17.2 mg/dL), and proportions of patients with glucose readings <70 mg/dL (14% vs. 56%) and <54 mg/dL (4.1% vs. 36%) detected by POC BG were significantly lower compared with CGM (all P < 0.001). Nocturnal and prolonged CGM hypoglycemia <54 mg/dL were 26% and 12%, respectively. The overall MARD was 14.8%, ranging between 11.4% and 16.7% for glucose values between 70 and 250 mg/dL and higher for 51-69 mg/dL (MARD 28.0%). The percentages of glucose readings within ±15%/15 mg/dL, ±20%/20 mg/dL, and ±30%/30 mg/dL were 62%, 76%, and 91%, respectively. Error grid analysis showed 98.8% of glucose pairs within zones A and B. CONCLUSIONS: Compared with POC, FreeStyle Libre CGM showed lower mean daily glucose and higher detection of hypoglycemic events, particularly nocturnal and prolonged hypoglycemia in hospitalized patients with T2D. CGM's accuracy was lower in the hypoglycemic range.

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.

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.