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Emedinexus 04 June 2025
Premixed insulin combines two types of insulin typically a rapid- or short-acting insulin with an intermediate- or long-acting insulin in a fixed ratio, allowing for both mealtime and basal glucose control with fewer daily injections. This formulation is primarily used in the management of type 1 and type 2 diabetes to simplify insulin regimens and improve patient adherence, especially for individuals with consistent meal patterns and daily routines (1). Common premixed insulin products include human insulin formulations and insulin analogues. These are generally administered two to three times daily, usually before meals, and are often delivered via pen devices, which are easy to use, offer adjustable dosing, and cause minimal injection discomfort, making them ideal for insulin-naïve patients or those with limited injection experience (1,2).While the convenience of premixed insulin is a clear advantage, its fixed insulin ratio can be a drawback. It limits the flexibility required for individualized glucose-lowering therapy, potentially leading to suboptimal glycemic control. In particular, patients may experience difficulty adjusting doses in response to varying dietary intake, activity levels, or insulin sensitivity. Additionally, variability in subcutaneous absorption and potential autoimmune responses have been proposed as factors that may further compromise glycemic stability in some individuals (1,3,4).To address these limitations, newer co-formulated insulin products have been developed. One such example is the combination of insulin degludec (a long-acting insulin) and insulin aspart (a rapid-acting insulin), which provides stable basal coverage alongside rapid mealtime glucose control in a single injection. This innovation offers greater pharmacokinetic stability and dosing flexibility compared to traditional premixed insulin formulations, and may help improve glycemic outcomes while retaining the ease of use associated with premixed regimens (1).
Clinical Outcomes and Guidelines Supporting the Use of Premixed Insulin Analogs
Premixed insulin analogs have demonstrated comparable efficacy and safety to basal and basal-bolus regimens in managing diabetes (5). A meta-analysis of 13 randomized controlled trials comparing premixed insulin with basal-bolus therapy found no significant differences in key outcomes, including HbA1c reduction, rates of hypoglycemia, weight change, and total daily insulin dose, despite the greater complexity and injection burden associated with basal-bolus regimens. In some studies, premixed insulin formulations, such as insulin lispro 25/75 and biphasic insulin aspart 70/30 (BIAsp 70/30), have shown better overall glycemic control than basal insulins like insulin glargine, both in insulin-naïve and previously treated patients (6). Clinical guidelines support the use of premixed insulin, particularly in primary care settings. The Indian National Consensus Group (INCG) recommends premixed insulins, especially analogs a simple, safe, and effective option for initiating and intensifying insulin therapy across all stages of diabetes(6,7). Similarly, guidance from the Royal Australian College of General Practitioners (RACGP) and the Research Society for the Study of Diabetes in India (RSSDI) endorses premixed insulin for patients with elevated fasting and postprandial glucose levels, or for those not achieving target HbA1c with basal insulin alone. In such cases, therapy may be intensified using premixed regimens instead of transitioning to more complex basal-plus or basal-bolus strategies. At all stages of insulin initiation and adjustment, these guidelines emphasize the importance of complementary lifestyle interventions, including appropriate nutrition and regular physical activity, to optimize glycemic outcomes (6).
References:
1. Xia Y, Hu Y, Ma JH. Premixed insulin: Advantages, disadvantages, and future. World J Diabetes [Internet]. 2025 Mar 15 [cited 2025 May 29];16(3). Available from: https://www.wjgnet.com/1948-9358/full/v16/i3/102526.htm
2. Moon SJ, Choe HJ, Kwak SH, Jung HS, Park KS, Cho YM. Comparison of Prevailing Insulin Regimens at Different Time Periods in Hospitalized Patients: A Real-World Experience from a Tertiary Hospital. Diabetes Metab J. 2021 Oct 20;46(3):439–50.
3. Wang W, Agner BFR, Luo B, Liu L, Liu M, Peng Y, et al. DUAL I China: Improved glycemic control with IDegLira versus its individual components in a randomized trial with Chinese participants with type 2 diabetes uncontrolled on oral antidiabetic drugs. J Diabetes. 2022;14(6):401–13.
4. Lingvay I, Handelsman Y, Linjawi S, Vilsbøll T, Halladin N, Ranc K, et al. Efficacy and Safety of Ideglira in Older Patients with Type 2 Diabetes. Endocr Pract. 2019 Feb 1;25(2):144–55.
5. Efficacy and safety of premixed insulin analogs in Asian patients with type 2 diabetes: A systematic review - Sheu - 2017 - Journal of Diabetes Investigation - Wiley Online Library [Internet]. [cited 2025 May 29]. Available from: https://onlinelibrary.wiley.com/doi/10.1111/jdi.12605
6. Kalra S, Czupryniak L, Kilov G, Lamptey R, Kumar A, Unnikrishnan AG, et al. Expert Opinion: Patient Selection for Premixed Insulin Formulations in Diabetes Care. Diabetes Ther. 2018 Dec 1;9(6):2185–99.
7. Das AK, Sahay BK, Seshiah V, Mohan V, Muruganathan A, Kumar A, et al. Indian National Consensus Group: National Guidelines on Initiation and Intensification of Insulin Therapy with Premixed Insulin Analogs.
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