• Users Online: 3898
  • Print this page
  • Email this page


 
 Table of Contents  
ORIGINAL ARTICLES
Year : 2022  |  Volume : 13  |  Issue : 2  |  Page : 171-176

Comparing time to intensification between insulin degludec/insulin aspart and insulin glargine: A single-center experience from India


Dr. Kovil’s Diabetes Care Centre, Andheri West, Mumbai, Maharashtra, India

Date of Submission18-Feb-2022
Date of Decision22-Apr-2022
Date of Acceptance25-Apr-2022
Date of Web Publication21-Jul-2022

Correspondence Address:
Dr. Rajiv Kovil
Dr. Kovil’s Diabetes Care Centre, Andheri West, Mumbai, Maharashtra 400058
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jod.jod_20_22

Rights and Permissions
  Abstract 

Background and Aims: The objective of the study was to compare the percent of patients with type 2 diabetes (T2D) requiring dose intensification and the time to dose intensification in patients on insulin degludec/insulin aspart (IDegAsp) versus those on basal insulin. Materials and Methods: Data were collected through retrospective chart review of patients with T2D being treated with insulin at a single center in India. The increase from once daily (OD) to twice daily dose or the addition of prandial insulin was considered as dose intensification. Chi-square test was conducted to compare the groups. Results: In the IDegAsp group (n = 515), 455 patients continued on the OD dose, and 60 patients (11.6%) were intensified. In the insulin glargine (IGlar) group (n = 173), 143 patients remained on the initial dose and 30 patients (17.34%) were intensified. Fewer patients on IDegAsp required treatment intensification than those on IGlar (P = 0.05). The time to treatment intensification (±standard deviation) was 11.98 ± 7.81 months in the IDegAsp group and 6.71 ± 6.86 months in the IGlar group. The time to treatment intensification was significantly longer in the IDegAsp than in the IGlar group (P = 0.0023). Conclusions: The study shows that significantly fewer patients on IDegAsp required dose intensification than those on IGlar. Additionally, the time to dose intensification was significantly delayed in patients on IDegAsp as compared to IGlar. However, HbA1c reduction with IGlar (nonintensified) was significant only at 6 months and failed to reach significance at 12 months, thereby pointing toward an early need for treatment intensification.

Keywords: Basal insulin, dose intensification, glycemic control, IDegAsp, IGlar, percent of patients intensified, time to intensification


How to cite this article:
Kovil R. Comparing time to intensification between insulin degludec/insulin aspart and insulin glargine: A single-center experience from India. J Diabetol 2022;13:171-6

How to cite this URL:
Kovil R. Comparing time to intensification between insulin degludec/insulin aspart and insulin glargine: A single-center experience from India. J Diabetol [serial online] 2022 [cited 2022 Aug 11];13:171-6. Available from: https://www.journalofdiabetology.org/text.asp?2022/13/2/171/351755




  Key Highlights: Top


This is the first retrospective study comparing IDegAsp and IGlar for dose intensification and time to dose intensification. Significantly fewer patients on IDegAsp require dose intensification compared with those on IGlar. The time to dose intensification is significantly delayed in patients on IDegAsp as compared to patients on IGlar.


  Introduction Top


Diabetes is a global health concern. According to the Diabetes  Atlas More Details, 10th edition by the International Diabetes Federation, approximately 537 million adults (20–79 years) in the world have diabetes.[1] This number is expected to rise to 643 million by 2030 and 783 million by 2045.[1] About 79% of individuals with diabetes live in low- and middle-income countries.[1] Diabetes is reaching epidemic proportions in South Asia, including India.[2],[3] India is projected to have approximately 101 million adults with diabetes by 2030 and 134 million by 2045.[3] About 90%–95% of adults with diabetes have type 2 diabetes (T2D).[4]

Pharmacotherapy in T2D usually starts with oral antidiabetic agents (OADs). With time, OADs fail to achieve the required euglycemia because of the progressive deterioration of β-cell function and the development of insulin resistance. This necessitates the need to initiate insulin.[5],[6],[7] Treatment with insulin not only lowers glycosylated hemoglobin (HbA1c) better than OADs but also reduces the glucotoxic effects of hyperglycemia.[5],[7],[8]

Basal insulin is usually the first insulin added to OADs to provide precise basal and postprandial blood glucose (PPG) control.[5],[9] However, as disease progresses, basal insulin needs further intensification either through additional mealtime short-acting insulin or by switching to insulin premixed formulations.[5],[9] This intensification increases the injection burden, complicates daily life, generates fear of hypoglycemia, reduces adherence to insulin therapy, and therefore leads to poor glycemic control.[5],[9],[10],[11],[12],[13],[14]

In such a scenario, a fixed-ratio coformulation of basal (long-acting) and bolus insulin (rapid-acting) could be a viable option for covering both basal and mealtime hyperglycemia using fewer injections than using basal and bolus insulin separately.[15],[16],[17],[18] Of the commonly used basal insulins, insulin degludec (IDeg) has the longest duration of action of >40 h, followed by insulin glargine (IGlar) (up to 24 h) and insulin detemir (IDet) (up to 20 h).[19],[20] Hence, a fixed-ratio coformulation with IDeg as a basal component can provide longer-lasting basal coverage than IGlar and IDet. A fixed-ratio coformulation of IDeg/insulin aspart (IDegAsp) has IDeg as the basal insulin component (70%), providing longer-lasting glycemic control than other commonly used basal insulins; and IAsp as the rapid-acting component (30%) that provides PPG control.[15],[16],[17]

Clinical and meta-analysis data on various populations (including Asians) show that IDegAsp initial and intensification regimes can effectively lower fasting plasma glucose, cause sustained basal glycemic control, and lower PPG without causing serious hypoglycemia and nocturnal hypoglycemia (NH).[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31] Evidence shows that IDegAsp is noninferior to premixed formulations and can be used as an alternative to basal–bolus and only basal insulin like IGlar.[32],[33],[34],[35] However, there are limited data on the proportion of patients on IDegAsp requiring treatment intensification and the time to treatment intensification as compared to patients on IGlar.


  Materials and Methods Top


This study was a retrospective chart review of patients with T2D being treated with insulin therapy. All male or female patients, 18 years and older with T2D being managed on insulin therapy at our center, and who could be followed-up for at least a year were included in the analysis. Data were collected from their charts between January 2017 and December 2020. Baseline demographic data, HbA1c, weight, type, dose, and dosing schedule of insulin were collected from the charts. The main objective of the study was to compare the percent of patients requiring dose intensification and the time to dose intensification in patients on IDegAsp versus those on basal insulin (IGlar). Insulin dose was titrated based on “Consensus on Insulin Dose and Titration Algorithms” recommended by the CID Expert Group.[36] Our center used the same insulin titration strategy for both the groups. Dose intensification in both groups was considered as switch from once daily (OD) to twice daily (BD) dose or the addition of prandial insulin.

Patients who switched multiple times from one treatment to another were excluded from the analysis. Additionally, patients who were already following the intensified regimen were not included in the analysis.

Descriptive statistics using average (± standard deviation [SD]) was used to describe continuous variables, and categorical variables were described using percentage. Chi-square T-test was used to determine the statistical significance of difference between IDegAsp and basal insulin groups for the change in HbA1c and weight over 6 months and 1 year. The proportion of patients requiring dose intensification and time to intensification between groups was also compared using chi-square T-test. A P value < 0.05 was considered statistically significant.


  Results Top


Baseline characteristics

One thousand and sixteen patients with T2D were eligible for the study. Of these, 874 were on IDegAsp and 279 on IGlar. After excluding patients who switched multiple times from one treatment to another and who were on intensified therapy at the beginning of the study (already on BD dose), 515 patients on IDegAsp and 173 on IGlar [Figure 1] were included in the analysis. The average baseline age, male/female ratio, HbA1c, and weight were comparable in the IDegAsp and IGlar groups [Table 1].
Figure 1: Flow chart of the study inclusion/exclusion criteria. BD, twice daily

Click here to view
Table 1: Baseline characteristics and change in HbA1c and weight of the whole study population during the study duration

Click here to view


Study outcomes

In the IDegAsp group (n = 515), 455 patients continued on the OD dose and 60 patients were intensified during the study period. Thus, 11.65% of patients in the IDegAsp group required treatment intensification. In the IGlar group (n = 173), 143 patients remained on the initial dose and 30 patients were intensified during the study period. Hence, 17.34% of patients on IGlar required treatment intensification. Chi-square test analysis showed that significantly fewer patients on IDegAsp required treatment intensification than those on IGlar (11.65% versus 17.34%; P = 0.05).

The time to treatment intensification (±SD) was 11.98 ± 7.81 months in the IDegAsp group and 6.71 ± 6.98 months in the IGlar group. Chi-square test analysis showed that the time to treatment intensification was significantly longer in the IDegAsp than in the IGlar group (11.98 ± 7.81 versus 6.74 ± 6.86; P = 0.0023) [Table 2].
Table 2: Proportion of patients intensified and time to intensification

Click here to view


Other findings

There was a significant reduction in the HbA1c level at 6 months in both the groups and at 1 year in the IDegAsp group [Table 1]. The mean HbA1c (±SD) in the IDegAsp group reduced from 9.76 ± 2.33 at baseline to 8.05 ± 1.12 and 8.14 ± 1.32 at 6 and 12 months, respectively (P < 0.0001 for both). The mean HbA1c (±SD) in the IGlar group reduced from 9.50 ± 1.91 at baseline to 7.65 ± 1.22 and 8.71 ± 2.34 at 6 and 12 months, respectively (P < 0.0001 and P = 0.10, respectively). There was no significant increase in weight in both the groups as shown in [Table 1].

Patients who continued on the IDegAsp OD dose had a significant reduction in the HbA1c level (baseline = 9.87 ± 2.37) at 6 months and 12 months. The mean HbA1c (±SD) at 6 and 12 months in the IDegAsp OD group was 7.80 ± 1.12 and 7.80 ± 1.12, respectively (P < 0.0001 for both). Patients who continued on the nonintensified dose of IGlar showed significant reduction in the mean HbA1c (±SD) (baseline = 9.52 ± 1.96) at 6 months but not at 12 months. The corresponding values were 7.36 ± 0.91and 8.48 ± 2.02, respectively (P < 0.0001 and 0.0797, respectively). There was no significant increase in weight in both the groups as shown in [Table 3].
Table 3: Change in HbA1c and weight of the nonintensified study population during the study duration

Click here to view



  Discussion Top


In our study, significantly fewer patients on IDegAsp OD dose required treatment intensification than those on basal insulin (11.65% versus 17.34%; P = 0.05). The time to treatment intensification was significantly lower in the IDegAsp than in the basal insulin group (11.98 ± 7.81 versus 6.71 ± 6.86; P = 0.0023). To the best of our knowledge, no other study compares the proportion of patients requiring treatment intensification and time treatment intensification on IDegAsp in comparison with basal insulin.

The literature comparing the percent of patients requiring treatment intensification and time to treatment intensification in the IDegAsp versus IGlar is largely lacking.

A 26-week, phase III study compared treatment intensification with IDegAsp BD dose with basal IDeg OD + prandial IAsp (two to four times a day).[28] Though HbA1c control, hypoglycemia, and NH episodes were similar across the two groups, total daily insulin dose used was significantly lower in the IDegAsp BD dose group than in the basal IDeg + prandial IAsp group (P < 0.05).[28] The IDegAsp BD dose group had a smaller change in body weight than the basal IDeg + prandial IAsp group. Patients in the IDegAsp BD dose group also had a significantly better social functioning than those in the basal IDeg + prandial IAsp group (P < 0.05),[28] because IDegAsp BD results in a good glycemic control and allows flexible dose timings and reduced injection burden.[15],[16],[37] For patients needing intensified therapy, IDegAsp BD can be easily followed by patients who find it difficult to adhere to complex drug regimes or multiple injections.[15],[37] For the healthcare professional, prescribing IDegAsp BD makes dose titration/intensification easy and control PPG spikes without the risk of hypoglycemia.[15],[16],[37],[38]

The literature shows that intensifying IDegAsp therapy from OD to BD dose or adding IAsp to IDegAsp provides similar glycemic control and fewer episodes of hypoglycemia including NH than multiple basal bolus insulin injections.[18],[28],[39] Evidence shows that IDegAsp provides superior glycemic control and better PPG control than basal insulin.[23],[40],[41],[42] Though an incident finding, and not the main objective of the study, our study too showed that patients on the IDegAsp-intensified group had significantly lower HbA1c at 6 months and 12 months (P < 0.001 for both time points), whereas HbA1c reduction in the IGlar-intensified group was not significant at any time point (P = 0.06 and 0.71 at 6 and 12 months, respectively). In patients with high baseline HbA1c, as seen in this study group, coformulations such as IDegAsp provide good HbA1c reduction, durable response, and fewer injection burden.[17] The glycemic control benefit in the IDegAsp group including the intensified population was achieved without a significant increase in weight. There were no reported cases of NH in our study in either group.

Basal insulin is often not optimally titrated in real-life settings.[43] To ensure that IDegAsp and IGlar were optimally titrated, the same titration strategy recommended by the CID Expert Group was followed in our center.[36] Also, a majority of patients took basal insulin at bed time as per our center’s prescribing policy, thus the risk of variable glycemic control among patients was avoided.

As is common with retrospective chart reviews, HbA1c and weight values were not available for all the patients at 6 and 12 months, and this could have affected the analysis. However, there is an abundant literature to show that IDegAsp causes significant reduction in blood glucose with no significant effect on weight.[24],[25],[40],[44] In line with the available literature, our study too showed that IDegAsp OD caused significant HbA1c reduction with no significant change in weight.

It is also important to note that weight change during the study duration was the only safety assessment in this study. IDegAsp safety in terms of the number of hypoglycemic events, especially after dose intensification, was not studied. However, IDegAsp has been found to be safer than other basal insulin formulations with fewer hypoglycemic events.[24],[25],[28],[39],[40],[44],[45],[46],[47],[48] Additionally, IDegAsp provides better long-term glycemic control than basal insulin with fewer NH episodes.[23],[49]

On the other hand, our study fills an important research gap and compares the percent of patients intensified and the time to intensification between IDegAsp and IGlar.


  Conclusions Top


Our study shows that significantly fewer patients on IDegAsp require dose intensification than those on IGlar. Additionally, the time to dose intensification is significantly delayed in patients on IDegAsp as compared to patients on IGlar. IDegAsp OD dose (nonintensified) resulted in significant reduction in HbA1c at 6 and 12 months with no significant increase in weight. However, HbA1c reduction with IGlar (nonintensified) was significant only at 6 months and failed to reach significance at 12 months, thereby pointing toward an early need for treatment intensification.

Acknowledgements

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work, and have given the final approval for the version to be published. The authors thank Dr. Punit Srivastava and Dr. Kokil Mathur of Mediception Science Pvt. Ltd (www.mediception.com) for providing medical writing support in the preparation of this article, and Novo Nordisk, India, for the writing grant. The authors take full responsibility for the content and conclusions stated in this article. Novo Nordisk neither influenced the content of this publication nor was it involved in the study design, data collection, analysis, interpretation, or review.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Ethics compliance

The study was approved by Kovil Clinic Institutional Review Board/Ethical Committee.



 
  References Top

1.
International Diabetes Federation. IDF Diabetes Atlas Tenth edition 2021—Diabetes Facts & Figures. International Diabetes Federation; 2021. Available from: https://diabetesatlas.org/. [Last accessed on 31 Mar 2022].  Back to cited text no. 1
    
2.
Kumar N, Puri N, Marotta F, Dhewa T, Calabro S, Puniya M, et al. Diabesity: An epidemic with its causes, prevention and control with special focus on dietary regime. Funct Foods Health Dis 2017;7:1-16.  Back to cited text no. 2
    
3.
International Diabetes Federation. IDF Diabetes Atlas. 9th ed. Brussels: International Diabetes Federation; 2019. Available from: https://www.diabetesatlas.org/upload/resources/material/20200302_133351_IDFATLAS9e-final-web.pdf. [Last accessed on 31 July 2021].  Back to cited text no. 3
    
4.
Bhupathiraju SN, Hu FB Epidemiology of obesity and diabetes and their cardiovascular complications. Circ Res 2016;118:1723-35.  Back to cited text no. 4
    
5.
Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of hyperglycemia in type 2 diabetes, 2015: A patient-centered approach: Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2015;38:140-9.  Back to cited text no. 5
    
6.
National Institute for Health and Care Excellence (UK). Type 2 Diabetes in Adults: Management. National Institute for Health and Care Excellence (UK); 2015. Available from: http://www.ncbi.nlm.nih.gov/books/NBK338142/. [Last accessed on 2 Aug 2021].  Back to cited text no. 6
    
7.
Handelsman Y, Bloomgarden ZT, Grunberger G, Umpierrez G, Zimmerman RS, Bailey TS, et al. American Association of Clinical Endocrinologists and American College of Endocrinology—Clinical practice guidelines for developing a diabetes mellitus comprehensive care plan—2015. Endocr Pract 2015;21 Suppl 1:1-87.  Back to cited text no. 7
    
8.
American Diabetes Association. 9. Pharmacologic approaches to glycemic treatment: Standards of medical care in diabetes—2021. Diabetes Care 2021;44(Supplement 1):S111-24.  Back to cited text no. 8
    
9.
Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, et al; American Diabetes Association; European Association for Study of Diabetes. Medical management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: A consensus statement of the American Diabetes Association and the European Association for the study of diabetes. Diabetes Care 2009;32:193-203.  Back to cited text no. 9
    
10.
Peyrot M, Barnett AH, Meneghini LF, Schumm-Draeger PM Insulin adherence behaviours and barriers in the multinational global attitudes of patients and physicians in insulin therapy study. Diabet Med 2012;29:682-9.  Back to cited text no. 10
    
11.
Ross SA, Tildesley HD, Ashkenas J Barriers to effective insulin treatment: The persistence of poor glycemic control in type 2 diabetes. Curr Med Res Opin 2011;27 Suppl 3:13-20.  Back to cited text no. 11
    
12.
Home P, Riddle M, Cefalu WT, Bailey CJ, Bretzel RG, Del Prato S, et al. Insulin therapy in people with type 2 diabetes: Opportunities and challenges? Diabetes Care 2014;37:1499-508.  Back to cited text no. 12
    
13.
Peyrot M, Rubin RR, Kruger DF, Travis LB Correlates of insulin injection omission. Diabetes Care 2010;33:240-5.  Back to cited text no. 13
    
14.
Vaag A, Lund SS, Lund S Insulin initiation in patients with type 2 diabetes mellitus: Treatment guidelines, clinical evidence and patterns of use of basal vs premixed insulin analogues. Eur J Endocrinol 2012;166:159-70.  Back to cited text no. 14
    
15.
Kalra S, Gupta Y Clinical use of insulin degludec: Practical experience and pragmatic suggestions. N Am J Med Sci 2015;7:81-5.  Back to cited text no. 15
    
16.
Demir T, Turan S, Unluhizarci K, Topaloglu O, Tukek T, Gogas Yavuz D Use of insulin degludec/insulin aspart in the management of diabetes mellitus: Expert panel recommendations on appropriate practice patterns. Front Endocrinol (Lausanne) 2021;12:616514.  Back to cited text no. 16
    
17.
John M, Gopinath D, Oommen T Co-formulations as the first injectable in type 2 diabetes: A review of efficacy, safety, and implications in clinical practice. Dubai Diabetes Endocrinol J 2020;26:139-51.  Back to cited text no. 17
    
18.
Philis-Tsimikas A, Astamirova K, Gupta Y, Haggag A, Roula D, Bak BA, et al. Similar glycaemic control with less nocturnal hypoglycaemia in a 38-week trial comparing the IDegAsp co-formulation with insulin glargine U100 and insulin aspart in basal insulin-treated subjects with type 2 diabetes mellitus. Diabetes Res Clin Pract 2019;147:157-65.  Back to cited text no. 18
    
19.
Standl E, Owen DR New long-acting basal insulins: Does benefit outweigh cost? Diabetes Care 2016;39 Suppl 2:S172-9.  Back to cited text no. 19
    
20.
Zhou W, Tao J, Zhou X, Chen H Insulin degludec, a novel ultra-long-acting basal insulin versus insulin glargine for the management of type 2 diabetes: A systematic review and meta-analysis. Diabetes Ther 2019;10:835-52.  Back to cited text no. 20
    
21.
Hirsch IB, Bode B, Courreges JP, Dykiel P, Franek E, Hermansen K, et al. Insulin degludec/insulin aspart administered once daily at any meal, with insulin aspart at other meals versus a standard basal-bolus regimen in patients with type 1 diabetes: A 26-week, phase 3, randomized, open-label, treat-to-target trial. Diabetes Care 2012;35:2174-81.  Back to cited text no. 21
    
22.
Hirsch IB, Franek E, Mersebach H, Bardtrum L, Hermansen K Safety and efficacy of insulin degludec/insulin aspart with bolus mealtime insulin aspart compared with standard basal-bolus treatment in people with type 1 diabetes: 1-year results from a randomized clinical trial (BOOST® T1). Diabet Med 2017;34:167-73.  Back to cited text no. 22
    
23.
Onishi Y, Ono Y, Rabøl R, Endahl L, Nakamura S Superior glycaemic control with once-daily insulin degludec/insulin aspart versus insulin glargine in Japanese adults with type 2 diabetes inadequately controlled with oral drugs: A randomized, controlled phase 3 trial. Diabetes Obes Metab 2013;15:826-32.  Back to cited text no. 23
    
24.
Franek E, Haluzík M, Canecki Varžić S, Sargin M, Macura S, Zacho J, et al. Twice-daily insulin degludec/insulin aspart provides superior fasting plasma glucose control and a reduced rate of hypoglycaemia compared with biphasic insulin aspart 30 in insulin-naïve adults with type 2 diabetes. Diabet Med 2016;33:497-505.  Back to cited text no. 24
    
25.
Fulcher GR, Christiansen JS, Bantwal G, Polaszewska-Muszynska M, Mersebach H, Andersen TH, et al; BOOST: Intensify Premix I Investigators. Comparison of insulin degludec/insulin aspart and biphasic insulin aspart 30 in uncontrolled, insulin-treated type 2 diabetes: A phase 3a, randomized, treat-to-target trial. Diabetes Care 2014;37:2084-90.  Back to cited text no. 25
    
26.
Kaneko S, Chow F, Choi DS, Taneda S, Hirao K, Park Y, et al; BOOST: Intensify All Trial Investigators. Insulin degludec/insulin aspart versus biphasic insulin aspart 30 in Asian patients with type 2 diabetes inadequately controlled on basal or pre-/self-mixed insulin: A 26-week, randomised, treat-to-target trial. Diabetes Res Clin Pract 2015;107:139-47.  Back to cited text no. 26
    
27.
Yang W, Ma J, Hong T, Liu M, Miao H, Peng Y. Insulin degludec/insulin aspart (IDegAsp) twice daily (BID) vs. biphasic insulin aspart 30 (BIAsp 30) BID—A randomized trial in Chinese patients with type 2 diabetes. Diabetes 2018;67(Supplement 1):91-LB.  Back to cited text no. 27
    
28.
Rodbard HW, Cariou B, Pieber TR, Endahl LA, Zacho J, Cooper JG Treatment intensification with an insulin degludec (IDeg)/insulin aspart (IASP) co-formulation twice daily compared with basal IDeg and prandial IAsp in type 2 diabetes: A randomized, controlled phase III trial. Diabetes Obes Metab 2016;18:274-80.  Back to cited text no. 28
    
29.
Hassanein M, Echtay AS, Malek R, Omar M, Shaikh SS, Ekelund M, et al. Efficacy and safety analysis of insulin degludec/insulin aspart compared with biphasic insulin aspart 30: A phase 3, multicentre, international, open-label, randomised, treat-to-target trial in patients with type 2 diabetes fasting during Ramadan. Diabetes Res Clin Pract 2018;135:218-26.  Back to cited text no. 29
    
30.
Haluzík M, Fulcher G, Pieber TR, Bardtrum L, Tutkunkardas D, Rodbard HW The co-formulation of insulin degludec and insulin aspart lowers fasting plasma glucose and rates of confirmed and nocturnal hypoglycaemia, independent of baseline glycated haemoglobin levels, disease duration or body mass index: A pooled meta-analysis of phase Iii studies in patients with type 2 diabetes. Diabetes Obes Metab 2018;20:1585-92.  Back to cited text no. 30
    
31.
Philis-Tsimikas A, Astamirova K, Gupta Y, Haggag A, Roula D, Bak BA, et al. Similar glycaemic control with less nocturnal hypoglycaemia in a 38-week trial comparing the IDegAsp co-formulation with insulin glargine U100 and insulin aspart in basal insulin-treated subjects with type 2 diabetes mellitus. Diabetes Res Clin Pract 2019;147:157-65.  Back to cited text no. 31
    
32.
Haahr H, Fita EG, Heise T A review of insulin degludec/insulin aspart: Pharmacokinetic and pharmacodynamic properties and their implications in clinical use. Clin Pharmacokinet 2017;56:339-54.  Back to cited text no. 32
    
33.
Kalra S Insulin degludec aspart: The first co-formulation of insulin analogues. Diabetes Ther 2014;5:65-72.  Back to cited text no. 33
    
34.
Kalra S, Gupta Y Injectable coformulations in diabetology. Diabetes Ther 2015;6:101-11.  Back to cited text no. 34
    
35.
Novo Nordisk A/S. Ryzodeg (insulin degludec/insulin aspart). Summary of product characteristics. European Medicines Agency; 2018. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/ryzodeg. [Last accessed on 2 Aug 2021].  Back to cited text no. 35
    
36.
Kovil R, Chawla M, Rajput R, Singh AK, Sinha B, Ghosal S, et al. Consensus on insulin dose and titration algorithms in ambulatory care of type 2 diabetes in India. J Assoc Physicians India 2017;65:17-30.  Back to cited text no. 36
    
37.
Glastras SJ, Cohen N, Dover T, Kilov G, Maclsaac RJ, McGill M, et al. The clinical role of insulin degludec/insulin aspart in type 2 diabetes: An empirical perspective from experience in Australia. J Clin Med 2020;9:1091.  Back to cited text no. 37
    
38.
Gerety G, Bebakar WM, Chaykin L, Ozkaya M, Macura S, Hersløv ML, et al. Treatment intensification with insulin degludec/insulin aspart twice daily: Randomized study to compare simple and step-wise titration algorithms. Endocr Pract 2016;22:546-54.  Back to cited text no. 38
    
39.
Bebakar WM, Chaykin L, Hersløv ML, Rasmussen S Intensification of IDegAsp twice daily (adding insulin aspart vs. switching to basal-bolus): Exploratory randomized trial in type 2 diabetes. Diabetes Ther 2017;8:197-205.  Back to cited text no. 39
    
40.
Heise T, Tack CJ, Cuddihy R, Davidson J, Gouet D, Liebl A, et al. A new-generation ultra-long-acting basal insulin with a bolus BOOST compared with insulin glargine in insulin-naive people with type 2 diabetes: A randomized, controlled trial. Diabetes Care 2011;34:669-74.  Back to cited text no. 40
    
41.
Cho KY, Nakamura A, Oba-Yamamoto C, Tsuchida K, Yanagiya S, Manda N, et al. Switching to once-daily insulin degludec/insulin aspart from basal insulin improves postprandial glycemia in patients with type 2 diabetes mellitus: Randomized controlled trial. Diabetes Metab J 2020;44:532-41.  Back to cited text no. 41
    
42.
Jang HN, Yang YS, Lee SO, Oh TJ, Koo BK, Jung HS Favorable glycemic control with once-daily insulin degludec/insulin aspart after changing from basal insulin in adults with type 2 diabetes. Endocrinol Metab (Seoul) 2019;34:382-9.  Back to cited text no. 42
    
43.
Kuritzky L, Reid TS, Wysham CH Practical guidance on effective basal insulin titration for primary care providers. Clin Diabetes 2019;37:368-76.  Back to cited text no. 43
    
44.
Özçelik S, Çelik M, Vural A, Aydın B, Özçelik M, Gozu H Outcomes of transition from premixed and intensive insulin therapies to insulin aspart/degludec co-formulation in type 2 diabetes mellitus: A real-world experience. Arch Med Sci 2021;17:1-8.  Back to cited text no. 44
    
45.
Meneghini L, Atkin SL, Gough SC, Raz I, Blonde L, Shestakova M, et al; NN1250-3668 (BEGIN FLEX) Trial Investigators. The efficacy and safety of insulin degludec given in variable once-daily dosing intervals compared with insulin glargine and insulin degludec dosed at the same time daily: A 26-week, randomized, open-label, parallel-group, treat-to-target trial in individuals with type 2 diabetes. Diabetes Care 2013;36:858-64.  Back to cited text no. 45
    
46.
Niskanen L, Leiter LA, Franek E, Weng J, Damci T, Muñoz-Torres M, et al. Comparison of a soluble co-formulation of insulin degludec/insulin aspart vs biphasic insulin aspart 30 in type 2 diabetes: A randomised trial. Eur J Endocrinol 2012;167:287-94.  Back to cited text no. 46
    
47.
Kumar A, Awata T, Bain SC, Ceriello A, Fulcher GR, Unnikrishnan AG, et al. Clinical use of the co-formulation of insulin degludec and insulin aspart. Int J Clin Pract 2016;70: 657-67.  Back to cited text no. 47
    
48.
Fulcher G, Mehta R, Fita EG, Ekelund M, Bain SC Efficacy and safety of IDegAsp versus BIAsp 30, both twice daily, in elderly patients with type 2 diabetes: Post hoc analysis of two phase 3 randomized controlled BOOST trials. Diabetes Ther 2019;10: 107-18.  Back to cited text no. 48
    
49.
Liebl A, Davidson J, Mersebach H, Dykiel P, Tack CJ, Heise T A novel insulin combination of insulin degludec and insulin aspart achieves a more stable overnight glucose profile than insulin glargine: Results from continuous glucose monitoring in a proof-of-concept trial. J Diabetes Sci Technol 2013;7:1328-36.  Back to cited text no. 49
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Key Highlights:
Introduction
Materials and Me...
Results
Discussion
Conclusions
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed240    
    Printed2    
    Emailed0    
    PDF Downloaded55    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]