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Comparing Pre-Mixed Insulin Regimen to Basal Bolus For Diabetes

Comparing Pre-Mixed Insulin Regimen to Basal Bolus For Diabetes

Hospitalized Patients – Comparing Pre-Mixed Insulin to Basal Bolus in Type 2 Diabetes

There are few studies looking at the safety and efficacy of pre-mixed insulin in the hospital setting.1 Pre-mixed insulin is only prescribed to patients in the outpatient setting.1

Current clinical guidelines recommend to use basal-bolus insulin regimen for the management of hyperglycemia in non-intensive care unit settings. “Despite the benefits of the basal-bolus regimen, many health care professionals consider this approach to be difficult to implement and inconvenient due to the high number of injections and the risk of hypoglycemia.”1

“It is not known whether patients with type 2 diabetes treated with premixed insulin prior to hospital admission should be switched to a basal-bolus insulin regimen or whether it is safe to continue with the same formulation during the hospital stay.”1

A randomized control trial comparing pre-mixed insulin to basal bolus insulin in hospitalized patients was conducted to determine major differences in blood glucose (BG) levels and frequency of hypoglycemic events (BG< 70mg/dl).1

The results of the study concluded that 64% of patients taking premixed insulin regimen experienced hypoglycemia compared to only 24% of patients receiving the basal-bolus regimen.1

For blood glucose levels there was no significant difference between premixed insulin regimen and basal-bolus insulin regimen because a BG target between 80 and 180 mg/dL before meals was achieved in 55.9% of BG readings in the basal-bolus group and 54.3% of BG readings in the premixed insulin group.1

Also, there was no difference in the length of hospital stay or mortality between treatment groups.1 Therefore, based on these results, it appears that it is safer to use a basal-bolus insulin regimen in the hospital and physicians may want to use this regimen instead of the premixed regimen.

Comparing Pre-Mixed Insulin to Basal Bolus in Reduction of A1c

Another systematic review looked at the reduction in the HbAlc levels to compare the efficacy between basal bolus insulin and premixed insulin regimens in randomized control trials.2

The results concluded that there was no difference in reduction in HbAlc between basal bolus insulin and premixed insulin regimens because there was a reduction in HbAlc of about 1.4% for both groups.2

Comparing Pre-Mixed Insulin to Basal Bolus For Quality of Life

A randomized control trial looked at the outcomes for improved quality of life, patient satisfaction, and glycemic control (3-day continuous HbAlc tested every 4-8 weeks) glucose while attempting to intensify treatment to achieve a HbA1c to below 7.0%.3

The study concluded that the mean HbA1c change was −0.39 ± 0.09% for glargine-glulisine and −0.05 ± 0.09% for premix, which implies that the reduction is close to similar for each. The patient satisfaction net benefit scale (0–100) improved from 51.1 to 60.5 ± 1.2 for glargine-glulisine and worsened to 45.4 ± 1.2 for premix (P< 0.0001).

The PS (patient satisfaction) regimen acceptance scale was comparable (P = 0.33). Overall QoL favored glargine-glulisine (P < 0.001), as did perceived health (P < 0.0001), symptom distress (P < 0.0001), general health perceptions (P < 0.01), and psychosocial (P < 0.02). CGM daily glucose mean, daily glucose SD (glycemic variability), and percent time over 140 mg/dl were lower for glargine-glulisine by 13.1 ± 2.7 mg/dl, 5.9 ± 1.4 mg/dl, and 7.3 ± 1.6%, respectively (all P < 0.0001), with no difference in CGM percent time below 70 mg/dl (P = 0.09). Symptomatic hypoglycemia rates were comparable. HbA1c, mean CGM daily glucose, and glycemic variability were independent predictors of PS net benefit.

From all this information, we can conclude that insulin intensification therapy benefits the basal-bolus group because “patient satisfaction was impacted more positively by improved QoL, reduced glucose variability, and better glycemic control with a basal-bolus regimen than negatively by the burden of additional injections”3

Comparing Pre-Mixed Insulin to Basal Bolus For Safety During Intensification

A 14 year narrative review was conducted to determine the outcomes of hypoglycemia and adverse events comparing pre-mixed (PM) insulin to basal bolus (BB) insulin regimens. The study concluded that BB insulin regimens were comparable to the PM insulin regimens in terms of hypoglycemia and adverse events. In terms of weight gain, two of seven studies showed significant weight gain in BB insulin regimen arms.4

What Can We Conclude From All These Studies?

Based on all the information provided, which regimen overall is better? Based on my own opinion, this is still variable based on the patient. In terms of efficacy, the regimens appear to be the same for both a reduction in blood glucose levels and reduction in HbA1c. However, in terms of safety the studies above have contradictory information.

One study concludes that patients prefer the basal-bolus regimen in terms of quality of life compared to the premixed insulin regimen when intensifying therapy to control blood sugar levels.

Based on analysis of all the studies it appears that basal-bolus may be overall better to use because one study concluded that patient satisfaction was higher with basal-bolus regimen when intensifying therapy and also glycemic control was slightly improved. The only negative outcome to consider is that patients that take the basal-bolus regimen have increased injections compared to pre-mixed insulin, which is only important with patients who are non-compliant.



(1) Bellido V, Suarez L, Rodriguez MG, et al. Comparison of Basal-Bolus and Premixed Insulin Regimens in Hospitalized Patients With Type 2 Diabetes. Diabetes Care. 2015;38(12):2211-6. Available from: Accessed November 13, 2018.

(2) Anyanwagu U, Mamza J, Gordon J, Donnelly R, Idris I. Premixed vs basal-bolus insulin regimen in Type 2 diabetes: comparison of clinical outcomes from randomized controlled trials and real-world data. Diabet Med. 2017;34(12):1728-1736. Available from: Accessed November 13, 2018

(3) Testa MA, Gill J, Su M, Turner RR, Blonde L, Simonson DC. Comparative effectiveness of basal-bolus versus premix analog insulin on glycemic variability and patient-centered outcomes during insulin intensification in type 1 and type 2 diabetes: a randomized, controlled, crossover trial. J Clin Endocrinol Metab. 2012;97(10):3504-14. Available from: Accessed November 13, 2018

(4) Ahmad NF, Nazar IM, Othman N, Penwalla NI. Safety of basal-bolus versus premixed insulin intensification regimens in the management of type 2 diabetes mellitus: A narrative review of a 14-year experience. Journal of Taibah University Medical Sciences. 2015;10(3):257-265. Available from: Accessed November 15, 2018.


Artur Dzhurinskiy
18 July, 2019

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My name is Artur Dzhurinskiy and I graduated from St. Louis College of Pharmacy in 2014 with a doctor of pharmacy degree. Through my academics I gained valuable experience learning about various medications that more:

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