Abstract
Aims:
Limited data exists about the use of insulin degludec in the hospital. This multicentre, non-inferiority, open-label, prospective randomised trial compared the safety and efficacy of insulin degludec-U100 and glargine-U100 for the management of hospitalized patients with type 2 diabetes.
Methods:
A total of 180 general medicine and surgery patients with an admission blood glucose (BG) between 7·8 – 22·2 mmol/L, treated with oral agents or insulin prior to 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 – 10·0 mmol/L. The primary end point was difference in the mean hospital daily BG between groups.
Results:
Overall, the randomization BG was 12·2 ± 2·9 mmol/L and HbA1c 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=0·9), proportion of BG in target range (54·5± 29% vs. 55·3 ± 28%, p=0·85), basal insulin (29·6 ± 13 vs 30·4 ± 18 units/day, p=0·85), length of stay (median (IQR): 6·7 (4·7–10·5) vs. 7·5 (4·7–11·6) days, p=0·61), hospital complications (23% vs. 23%, p=0·95) between treatment groups. There were no differences in the proportion of patients with BG <3.9 mmol/L (17% vs. 19%, p=0·75) or < 3·0 mmol/L (3·7% vs. 1·3%, p=0·62) between degludec and glargine.
Conclusion:
Hospital treatment with degludec-U100 or glargine-U100 are equally safe and effective for the management of hyperglycaemia in general medicine and surgery patients with type 2 diabetes.
ClinicalTrials.gov identifier: NCT03336528
Keywords: Glargine, degludec, hypoglycaemia, hospital care, inpatient management
Introduction
A large body of evidence supports that in hospitalized patients, the presence of hyperglycaemia and diabetes is associated with increased risk of complications and mortality (1–3). Observational and randomised clinical trials (RCTs) in both critically ill and in non-critically ill (non-ICU) medicine and surgery patients have shown that improvement of glycaemic control reduces length of hospital stay, systemic infections and short- and long-term mortality (4–6). We and others have reported that treatment with basal bolus regimens using long-acting insulin analogs results in greater improvement in glycaemic control and a reduction in the frequency of hospital complications, including postoperative wound infection, pneumonia, bacteraemia, acute kidney injury, and respiratory failure (6–9). In addition, the use of basal bolus regimen with glargine U100 is effective and has been associated with low rates of hypoglycaemic events in medicine (7) and surgery patients with type 2 diabetes (T2D) (6). Based on these studies, clinical practice guidelines for the management of hyperglycaemia in non-ICU settings have favoured the use of basal and prandial insulin regimens with insulin analogs for most hospitalized patients with T2D (10, 11).
Insulin degludec is a novel long-acting basal insulin analog with a half-life of ~ 25 hours and a duration of action > 40 hours with no peaks (12, 13). Several RCTs using a treat-to-target protocol have demonstrated comparable improvements in glycaemic control between degludec and glargine U100 insulin in ambulatory patients with type 1 and type 2 diabetes (13–15). Insulin degludec, however; in both randomised and observational studies, has been associated with significant lower rates of overall symptomatic and nocturnal hypoglycaemic events (14, 16, 17), as well as less day- to-day and within-day glycaemic variability compared to other basal insulin analogs (13, 14, 18). The safety profile and lower rate of hypoglycaemia make insulin degludec an attractive alternative to glargine for the hospital management of patients with diabetes (19, 20). The unique pharmacokinetic features of insulin degludec require further investigation in the hospital setting; including how a prolonged duration of action and the steady-state concentration that is achieved after the second or third day of therapy (15, 20), may limit the ability to make day-to-day adjustments in insulin dosage. Accordingly, we conducted a non-inferiority randomised controlled trial to compare the safety and efficacy of a basal bolus regimen with degludec U100 and glargine U100 in hospitalized, medicine and surgery patients with T2D.
Materials and Methods
Study Design
This multicentre, prospective, non-inferiority, open label, randomised controlled study was conducted at three academic medical centres in the U.S., including Emory University, Atlanta, GA; Providence Health Care, Spokane, WA; and Icahn School of Medicine at Mount Sinai, New York, NY. The institutional review boards at Emory University and participating institutions approved the study protocol. Informed consent was obtained from all subjects during hospitalization. This trial is registered with clinicaltrials.gov, number NCT03336528.
Participants
We screened male or female patients > 18 years of age, with a known history of T2D, receiving treatment prior to admission with diet alone, oral monotherapy, any combination of oral antidiabetic agents, short-acting GLP1-RA (exenatide, liraglutide) or insulin therapy (except for degludec and glargine U300), admitted with acute or chronic medical illnesses, emergency and elective surgical procedures or trauma. Due to the design of this study, there was not a run-in period. We included patients with an admission BG > 7·8 mmol/L and < 22·2 mmol/L with an estimated length of hospital stay (LOS) ≥ 3 days. There was no upper limit on home insulin dose.
Patients treated with degludec, glargine U300 or with long-acting GLP-1-RA (dulaglutide, albiglutide and weekly exenatide) prior to admission were excluded. In addition, we excluded subjects with hyperglycaemia but without a known history of diabetes (stress hyperglycaemia), type 1 diabetes, subjects with a history of diabetic ketoacidosis and hyperosmolar hyperglycaemic state, or ketonuria, acute critical or surgical illness admitted to the ICU or expected to require admission to the ICU, clinically relevant hepatic disease (liver cirrhosis or portal hypertension), corticosteroid therapy, or advanced chronic kidney disease (estimated glomerular filtration rate [eGFR< 30 ml/min/1.73m2). Patients with mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study, pregnancy or breast-feeding and known or suspected insulin allergy were also excluded from participation. Participants meeting criteria were approached by the study team, after approval by primary care teams. After explaining the study details, all participants provided written informed consent before the start of any study procedures.
Randomisation and Masking
Patients were randomly assigned to receive either a basal-bolus regimen with insulin degludec U100 (Tresiba, Novo Nordisk) or to glargine U100 (Lantus, Sanofi-Aventis) insulin. Treatment assignment was coordinated by a research pharmacist, a member of the investigational drug service and not part of the study at each institution following a computer-generated block randomisation table created by a statistician (LP), based at Emory University School of Public Health. Due to the nature of the study, investigators and participants were not blinded to the treatment allocation.
Procedures
Patients were managed for medical and surgical problem(s) by their primary care team who received a copy of the assigned treatment protocol. Management of the insulin regimen was directed by the study team following a basal bolus insulin regimen previously reported (appendix section) (6, 7, 8, 22, 23). In brief, subjects treated with insulin prior to admission received 80% of the total daily outpatient insulin dose. Insulin naïve patients discontinued oral agents and received a starting total daily dose (TDD) of 0.4 U/kg/day for BG: 7·8 mmol/L - 11·1 mmol/L and 0.5 U/kg/day for BG: 11·2 mmol/L and 22.2 mmol/L. The starting TDD was reduced to 0.3 U/kg/day in patients ≥ 70 years or with a GFR < 60 ml/min/1.73m2. Both groups were treated with basal bolus regimen given half of TDD as basal (degludec or glargine) once daily and half as insulin aspart (Novolog, Novo Nordisk) insulin divided in three equal doses before meals. Patients with poor oral intake or who were kept NPO (nil per os or nothing by mouth) received the basal dose, but prandial dose was held (8). All patients also received additional aspart doses to correct for hyperglycaemia up to 4 times a day as per a standard hospital protocol (appendix section). Glucose levels were assessed by capillary point of care testing before meals and bedtime. Insulin dose was adjusted daily to maintain a fasting BG < 7·8 mmol/L and pre-meal BG < 10·0 mmol/L, while avoiding hypoglycaemia < 3·9 mmol/L (11).
Study Outcomes
The overall objective was to determine differences in hospital glycaemic control, as measured by mean daily blood glucose concentration and frequency of hypoglycaemia, in medicine and surgery patients with T2D treated with basal bolus regimen with insulin degludec or glargine once daily plus rapid-acting insulin before meals.
The primary efficacy endpoint of the study was to determine if the use of degludec U100 was non-inferior to glargine U100, as measured by mean daily BG concentration during the hospital stay. Safety endpoints were to compare differences on the number of patients with hypoglycaemia (< 3·9 mmol/L), clinically significant (< 3·0 mmol/L) and severe hypoglycaemia (< 2·2 mmol/L); proportion of BG readings within target of 3·9 mmol/L - 10·0 mmol/L before meals; proportion of BG readings between 3·9 mmol/L - 10·0 mmol/L before meals without hypoglycaemia, number of episodes of severe hyperglycaemia (BG > 13·3 mmol/L) after the first day of treatment, total daily dose of insulin including basal, bolus and correctional insulin, treatment failure (defined as a mean daily BG > 15.5 mmol/L in 2 consecutive days or any glucose value > 22·2 mmol/L) and length of hospital stay. As exploratory outcomes, we also assessed differences in complications including cardiovascular events (myocardial infarction, cardiac arrhythmia requiring medical treatment, or cardiac arrest), acute kidney injury (defined as a clinical diagnosis with increment in serum creatinine ≥ 0.3 mg/dL from baseline or ≥1.5 times baseline creatinine, and hospital mortality.
Statistical analysis
The overall hypothesis was that patients with T2D treated with insulin degludec U100 and glargine U100 will experience similar improvement (non-inferior) in mean daily BG levels during the hospital stay. To show the non-inferiority of degludec and glargine in terms of glycaemic control, we set the equivalence margin as 1 mmol/L (18 mg/dL), from a view that a difference <1·0 mmol/L is usually not considered as clinically significant (6–8, 23). Based on the results of previous basal bolus insulin trials in hospitalized patients with T2D (6–8), it is reasonable to assume the standard deviation of mean daily BG is bounded above by 2·5 mmol/L. Assuming the true BG difference between the treatment groups is zero, and using one-sided, two-sample t-tests, we estimated that 78 subjects were required for each treatment group to achieve 80% power, with alpha=0·05. Accounting for 10–15% attrition rate, we needed to recruit 90 patients per treatment group.
Statistical analysis followed a modified intention-to-treat analysis, including all patients receiving at least 2 days of basal insulin. To compare continuous baseline and clinical characteristics and outcomes between the two study groups we used nonparametric Wilcoxon tests. For discrete baseline and clinical characteristics and outcomes (such as hypoglycaemia outcomes), we conducted nonparametric comparisons based on a two-sided Chi-square test (or Fisher’s exact test). A p value less than 0.05 is considered as statistically significant. Data was presented as mean (SD) for continuous variables and count (percentage) for discrete variables. Statistical analyses were performed with SAS version 9.4. A data safety monitoring committee, including 2 clinical investigators not related to the study, performed interim analyses for safety every six months.
Role of Funding Source:
The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Results
Between January 2018 and December 2020, we approached a total of 304 subjects eligible, who were admitted to general medicine and surgery services; of them, 182 participants were consented for the study. Two subjects were considered screen failures and excluded without randomisation. A total of 92 participants were randomised to receive insulin degludec; of them ten patients were excluded: one patient had a positive drug screen and history of substance abuse, one patient did not receive study medication, and eight patients received a single dose of study drug or were discharged less than 48 hours after randomisation. A total of 88 participants were allocated to glargine therapy, of them nine were excluded: one patient received high doses of corticosteroid, one did not receive study medication and six patients received a single dose of study drug and were discharged less than 48 hours after randomisation. In sum, a total of 161 participants were included in the intention-to-treat analysis, including 82 participants in the degludec U-100 group and 79 participants in the glargine U-100 group (Figure 1).
Figure 1:
Study Flow (Participant Disposition)
Demographics and clinical characteristics are shown in Table 1. Treatment groups were balanced without differences in clinical characteristics including age, sex, racial distribution, BMI, or duration of diabetes (Table 1). More patients were recruited from medicine services (n: 131, 76%) than surgery services (n: 38, 24%). There were no differences in preadmission antidiabetic therapy with most patients in both groups treated with oral antidiabetic drugs or oral drugs plus insulin therapy.
Table 1:
Baseline Characteristics
| Degludec U100 (n=82) | Glargine U100 (n=79) | |
|---|---|---|
| Age, years | 55·6 ± 12 | 56·7 ± 10 |
| Sex (M/F), n (%) | 47/35 (57/43) | 54/25 (68/32) |
| Race, n (%) | ||
| Black | 58 (71) | 56 (71) |
| White | 16 (20) | 18 (23) |
| Other | 8 (10) | 5 |
| BMI, kg/m2 | 35·5 ± 8·9 | 35·4 ± 12·3 |
| Weight, kg | 103·3 ± 27·5 | 105·3 ± 29·4 |
| Diabetes duration, years | 12·8 ± 9 | 13·3 ± 9 |
| HbA1c, mmol/mol | 85 ± 21 | 82 ± 23 |
| Admission BG, mmol/L | 13·0 ± 4·5 | 12·8 ± 4·4 |
| Randomisation BG, mmol/L | 12·2 ± 2·8 | 12·1 ± 3·1 |
| Home diabetes treatment, n (%) | ||
| No treatment | 7 (8.5) | 10 (13) |
| Oral antidiabetic agents | 18 (22) | 15 (19) |
| Insulin only | 30 (37) | 32 (41) |
| Insulin + oral antidiabetic agent | 27 (33) | 21 (27) |
| GLP1-RA | 0 (0) | 1 (1) |
| Home insulin dose, unit/Kg/day | 0·63 ± 0·35 | 0·71 ± 0·44 |
| Hospital service, n (%) | ||
| Medicine | 68 (73) | 63 (80) |
| Surgery | 22 (27) | 16 (20) |
Data presented from the modified intention-to-treat population
For the entire cohort, the mean BG on admission was 12·9±4·5 mmol/L and at randomization was 12·2 ± 2·9 mmol/L, admission HbA1c was 84±22·3 mmol/mol (9·82±2·0%), and majority of patients were treated with insulin at home (n= 110, 69%). The mean randomization BG and HbA1C in the degludec group (12·2 ± 2·8 mmol/L, HbA1c 85±21.9 mmol/mol [9.96±2.0%]) were similar to patients in the glargine group (12·2±3·0 mmol/L and 82±23 mmol/mol [9·67±2·1%], p =0·76, and p=0·32, respectively. Both treatment regimens resulted in similar mean daily BG concentrations during the hospital stay (Figure 1), with no significant difference in mean daily BG (10·0±2·1 vs. 10·0±2·5 mmol/L, p=0·91 or in glucose concentration before meals and at bedtime (Figure 1 A and 1 B). Similarly, there were no differences in the proportion of BG in target range of 3·9 to 10·0 mmol/L (54·5±29% vs. 55·3±28%, p=0·85), between patients treated with degludec and glargine insulin.
The total daily dose of insulin, including amount of basal and prandial insulin dose is shown in Table 2. For the entire cohort, the total daily dose was 57·88±30·53 U/day (0·57 ± 0·27 U/Kg/day), with 29·96±15·99 U/day of basal and 11·69±9·86 U/day of aspart insulin before meals and a mean of 3·77±2·75 U/day of correction doses (Table 2). There were no differences on the amount of insulin administration between groups. In the degludec group, the total daily dose was 56·36±24·26 U/day, p=0·92 (0·56±0·22 U/day/Kg, p= 0·61), given as basal degludec insulin 29·55±13·30 U/day, prandial aspart 10·98 ± 8·60 U/day and 3·60±2·25 U/day as supplemental insulin before meals. In the glargine group, the total daily dose was 59·45±36·0 U/day (0·58±0·32 U/Kg/day), given as basal dose of 30·39±18·44 U/day, prandial aspart 12·44±11·01 U/day and 3·94±3·19 U/day as supplemental aspart before meals.
Table 2:
Primary and Secondary Outcomes: Glycemic Outcomes, Hypoglycaemia, Insulin Doses and Complications
| Degludec U100 (n=82) | Glargine U100 (n=79) | p-value | |
|---|---|---|---|
| Glycemic Outcomes | |||
| Mean hospital BG, mmol/L | 10·3 ± 2·1 | 10·3 ± 2·5 | 0·81 |
| Mean BG after day 1, mmol/L | 10·0 ± 2·1 | 10·0 ± 2·5 | 0·77 |
| Percent BG 3·9–10·0 mmol/L (70–180 mg/dL) | 50·3 ± 1·5 | 52·2 ± 1·4 | 0·65 |
| Percent BG 3·9–10·0 mmol/L (70–180 mg/dL) after Day 1, % | 50·3 ± 1·5 | 55·3 ± 1·4 | 0·85 |
| BG < 3·9 mmol/L (70 mg/dL), n (%) | 14 (17) | 15 (19) | 0·75 |
| BG < 3·0 mmol/L (54 mg/dL), n (%) | 3 (3.7) | 1 (1.3) | 0·62 |
| BG ≤ 2·2 mmol/L (40 mg/dL), n (%) | 0 (0) | 0 (0) | N/A |
| BG > 13·3 mmol/L (240 mg/dL), n (%) | 52 (63) | 47 (59) | 0·61 |
| Insulin dose | |||
| Total daily, units/day | 56·4 ± 24 | 59·5 ± 36 | 0·92 |
| Total basal, units/day | 29·6 ± 13 | 30·4 ± 18 | 0·85 |
| Total prandial, units/day | 10·9 ± 8·6 | 12·4 ± 11 | 0·41 |
| Total supplement (SSI), units/day | 3·6 ± 2·2 | 3·9 ± 3·2 | 0·97 |
| Total daily, units/Kg/day | 0·56 ± 0·22 | 0·58 ± 0·32 | 0·61 |
| Total basal, units/Kg/day | 0·29 ± 0·13 | 0·30 ± 0·17 | 0·35 |
| Total prandial, units/Kg/day | 0·11 ± 0·08 | 0·12 ± 0·11 | 0·49 |
| Total supplement (SSI), units/kg/day | 0·04 ± 0·03 | 0·04 ± 0·04 | 0·99 |
| Complications | |||
| Composite | 19 (23) | 18 (23) | 0·95 |
| Mortality, n (%) | 0 (0) | 1 (1·3) | 0·49 |
| Acute kidney injury, n (%) | 5 (6·1) | 10 (13) | 0·18 |
| Pneumonia, n (%) | 1 (1·1) | 0 (0) | >0·99 |
| Transfer to ICU | 1 (1·2) | 0 (0) | >0·99 |
| Length of stay (days), Median (IQR: Q1, Q3) | 6·7 (4·7, 10·5) | 7·5 (4·7,11·6) | 0·61 |
| Treatment failure, n (%) | 8 (9·8) | 10 (13) | 0·62 |
There were no differences in the rates of hypoglycaemia during the hospital stay between groups, Table 2. A total of 14 patients (17%) had a BG < 3·9 mmol/L and 3 patients (3·7%) had a clinically significant hypoglycaemia < 3·0 mmol/L in the degludec group, compared to 15 (19%) with hypoglycaemia < 3·9 mmol/L (p= 0·75) and 1 patient (1·3%) with < 3·0 mmol/L (p= 0·62) in the glargine treated group. There were no patients in either group with severe hypoglycaemia ≤ 2·2 mmol/L.
In an exploratory analysis to evaluate the efficacy of degludec (titrated daily) among patients with severe hyperglycaemia, we performed post hoc analyses between degludec and glargine groups, stratified by a randomization BG ≤ 11·1 mmol/L (n= 55, 34.2%) or BG ≥ 11·1 mmol/L (n=106, 65·8%) and admission HbA1c ≤ 75 mmol/mol (<9%) (n= 69, 42·8%) and > 75 mmol/mol (>9%) (n=92, 57·1%). There were no significant differences in mean daily glucose, proportion of BG in target 3·9–10·0 mmol/L or hypoglycaemia < 3·9 mmol/L and < 3·0 mmol/L between treatment groups.
There were no differences between groups in length of hospital stay (median (IQR): 6·7 (4·7, 10·5) in the degludec vs. 7·5 (4·7,11·6) days in the glargine group, p=0·61 (Table 2) or in the frequency of the composite outcome of complications including infections, acute respiratory failure, acute kidney injury, surgical re-intervention, and cardiovascular events (23% [n: 19] vs. 23% [n: 18], p=0·95), or in the number of treatment failures (9·8% [n: 8] vs 13% [n: 10], p=0·62) between degludec and glargine groups (Table 2).
Discussion
This prospective, multicentre, randomised non-inferiority designed clinical trial compared the safety and efficacy of insulin degludec U100 and glargine U100 for the inpatient management of patients with T2D. Our study met the non-inferiority criteria and demonstrated that treatment with a basal bolus regimen with degludec, titrated daily to a target glucose: 3·9 – 10·0 mmol/L (70–180 mg/dL), resulted in similar mean daily BG concentration, frequency of hypoglycaemia, length of stay and frequency of complications during hospitalization compared to a glargine-based regimen in medicine and surgery patients with T2D.
Insulin is the cornerstone for the management of hyperglycaemia in the hospital setting. A regimen of insulin with basal, prandial, and correction components (basal-bolus regimen) is the preferred treatment for noncritically ill hospitalized patients with good nutritional intake. Basal insulin plus bolus correction regimen is preferred for hospitalized patients with poor oral intake (8, 11). During the past decade, several randomised controlled studies have reported on the efficacy and safety of basal bolus regimen for the hospital management of patients with T2D. Two randomised multi-center trials reported that basal bolus treatment with glargine U100 insulin improved glycemic control and reduced the rate of hospital complications compared to sliding scale regular insulin regimens in general surgery patients with T2D (6–7). Two additional studies using basal bolus regimen with glargine insulin reported similar glycaemic control but lower rates of hypoglycaemic events when compared to neutral protamine Hagedorn (NPH) insulin (24) and premixed insulin formulations combined with regular insulin (25). A more recent RCT using the new long-acting glargine U300 in hospitalized patients with T2D reported no differences in mean daily blood glucose compared to glargine U100 formulation, no differences in the rate of hypoglycaemia < 3·9 mmol/L, but lower rates of clinically significant hypoglycaemia < 3·0 mmol/L (26).
The present study builds on the information available on the efficacy and safety of basal bolus regimen with the use of degludec, a long-acting basal insulin formulation for the inpatient management of general medicine and surgery with T2D. Two small studies reported preliminary findings on the use of insulin degludec in the hospital. A study compared degludec U100 and glargine U100 in electively admitted patients for glycaemic control optimization and reported no differences in mean daily glucose, glycaemic variability or in the rate of hypoglycaemia between insulin groups (27). An additional proof of concept study showed the feasibility of using degludec in 26 patients (13 with and 13 without diabetes) receiving enteral and/or parenteral nutrition (28). Our results included a complex cohort of patients with uncontrolled diabetes, with a mean admission HbA1c > 75 mmol/mol (9%), with over 12 years of diabetes duration, with > 65% of patients previously treated with insulin at a mean total insulin dose > 0·65 units/kg/day prior to admission. Despite this clinically challenging population, most study participants treated with degludec and glargine insulin achieved glycaemic control with low frequency of hypoglycaemia during the hospital stay.
Given the novel pharmacokinetics of long-acting duration of action and the steady state reached after second or third day of therapy (15, 20), there was a need for a prospective study in order to assess the safety of daily insulin titration in the hospital setting (i.e. effect of insulin stacking). We report that daily titration of degludec was safe with low rates of hypoglycaemia. A potential explanation for the low hypoglycaemia rates could be the more relaxed inpatient glucose targets compared to previous ambulatory trials, as well as the mechanism of protraction of degludec, resulting in a slow release of degludec from the subcutaneous injection depot into the circulation (29). Moreover, we did not observe a differential effect of degludec compared to glargine on subgroup analyses by HbA1c categories (≤ 75 mmol/mol vs >75 mmol/mol) or admission glucose (≤11·1 vs > 11·1 mmol/L) suggesting that both insulin formulations are comparable in a wide and heterogeneous group of hospitalized patients with T2D.
While our study provides novel information, it has some limitations. We did not include patients with type 1 diabetes, a population in which degludec has shown benefits in glycaemic variability in the ambulatory setting. Our study was not powered to determine differences in complications between groups, but overall rates of hypoglycaemia and complications were low. Our study design was not blinded, and the proportion of BG in target range of 3·9 to 10·0 mmol/L was only ~55% - albeit with no differences between allocation groups. We monitored glycaemic control by the current standard of care using capillary glucose testing before meals and bedtime, which provides a limited assessment on the rate of nocturnal hypoglycaemia (30). Further studies using continuous glucose monitoring may improve assessment of nocturnal and asymptomatic hypoglycaemia in hospitalized patients.
In conclusion, basal bolus treatment with degludec U100, titrated daily to target glucose of 3·9 – 10·0 mmol/L (70 – 180 mg/dL), resulted in similar mean daily BG concentration, frequency of hypoglycaemia, length of stay and hospital complications compared to glargine U100 in general medicine and surgery patients with T2D.
Figure 2:
Daily Blood Glucose Levels During Hospitalization in Patients treated with Degludec U100 and Glargine U100.
Figure 2 A: Mean daily blood glucose concentrations
Figure 2B: Mean blood glucose before meals and bedtime Data presented as mean ± SD.
Acknowledgments/Author Contribution
RJG, FJP, PV, RA, DL, MF, AM, GD, SC, KRT reviewed and edited the initial research proposal, conducted the study, reviewed the data and analysis, and edited the manuscript. MAU, KWZC, BA, MCPG screened, recruited and followed participants in the study and reviewed the data. LP generated the random allocation sequence and did the statistical analysis. GEU wrote the initial research proposal, critically reviewed research data and co-wrote the manuscript with RJG. GEU is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Funding
This work was an investigator-initiated study, with unrestricted research support provided by Novo Nordisk to Emory University. The funding source had no input on the design of the study, interpretation of the results or manuscript preparation.
RJG is supported in part by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institute of Health (NIH) under award numbers P30DK111024-04S2 and 1K23DK123384-02, outside the submitted work. RJG received unrestricted research support (to Emory University) for investigator-initiated studies from Novo Nordisk and Dexcom, and consulting fees from Abbott Diabetes Care, Sanofi, Novo Nordisk, Eli Lilly and Valeritas, outside the submitted work. PV is supported in part by National Institute of Health grant 1K23DK113241 and has received consulting fees from Merck and Boehringer-Ingelheim. FP reports grants from Merck and Dexcom, consultant/advisory fees from Merck, Astra Zeneca, Lilly, Boheringer Ingelheim, and Sanofi. FJP is supported by grants from National Institutes of Health (grant P30-DK-111024) from NIDDK, and from National Institutes of Health (grant 1K23GM128221-01A1) from the National Institute of General Medical Sciences, outside the submitted work. GMD is supported NIH under award number 1K23DK122199-01A1, and received research support for studies (to Emory University) from Insulet Corp, outside the submitted work. MF is supported NIH/NIDDK under award number 1K23-124647A. RA has received consulting fees from Boehringer Ingelheim, outside the submitted work. KRT is supported by research grants from NIH/NCATS 4UL1TR00426-10 and NIH/NIDDK 1U2CDK114886-01, 5UM1DK100846-03, 2U01DK10086-07, 1U54DK083912, 2UC4DK101108-02, and CDC grant 75D301-19-Q-69877, and has served as a consultant for Eli Lilly and Company, Boehringer Ingelheim, Astra Zeneca, Gilead, Goldfinch Bio, Novo Nordisk, Bayer, and Janssen. GEU is partly supported by research grants from the NIH/NATS UL1 TR002378 from the Clinical and Translational Science Award program, and NIH/NIDDK 1P30DK111024-01 from NIH and National Center for Research Resources. GEU has received unrestricted research support for research studies (to Emory University) from Novo Nordisk, Astra Zeneca and Dexcom Inc.
Footnotes
Disclosures
No potential conflict of interest relevant to this article was reported by DLW, MF, GD, SC, MAU, KWZC, BA, MCPG, and LP.
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