Switch From Rapid-Acting to Concentrated Insulin Improves Glycemic Control

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Insulin delivered by continuous subcutaneous insulin infusion is often effective in people with type 2 diabetes vs multiple daily injections, but many still do not reach glycemic targets. Investigators sough the reason behind this challenge.

People with type 2 diabetes (T2D) who had inadequate glycemic control with continuous subcutaneous insulin infusion (CSII) pump therapy improved after switching from rapid-acting to concentrated regular insulin, according to study findings published in Diabetes and Metabolism.

The retrospective study included 65 patients (mean age, 62.3±8.3 years) with T2D from 6 French centers. Patients enrolled in the study had previously received insulin pump therapy and were switched from 100 U/ml rapid-acting insulin analogue (U-100) to 500 U/ml (U-500) human regular insulin (provided by pharmaceutical manufacturer Eli Lilly, Inc.) between 2011 and 2017.

Data collected from the patients’ medical records included glycated hemoglobin ((HbA1c), lipid levels, liver biomarkers, weight, insulin total daily dose (TDD), declared hypoglycemic episodes, and blood glucose as measured by continuous glucose monitoring (CGM).

In the entire 65-person cohort, the mean duration of diabetes was 20.7±9.3 years, and the mean duration of insulin treatment was 12.9±6.7 years. Most patients had cardiovascular risk factors such as hypertension (95.4%) and dyslipidemia (90.8%). At baseline, the mean HbA1c was 9.03±1.58.

After patients switched to U-500, mean HbA1c decreased from baseline by -0.96% at 1 year (95% CI, -1.33 to -0.43; P <.0001) and -0.95% at 3 years (95% CI, -1.49 to -0.40; P =.002). Additionally, the proportion of patients that had an HbA1c level ≤8% significantly increased from 26% with U-100 to 42% at 6 months (P <.02) and 60% at 3 years (P <.02) with U-500.

Mean body weight increased by 2.3±5.6 kg at 1 year (95% CI, 0.64-3.84; P <.01) and 4.8±8.0 kg (95% CI, 0.94-8.69; P =.02) at 3 years. Mean TDD increased by 13% from baseline to 6 months (P <.01) and 19% at 1 year (P <.001).

During follow-up, declared non-severe hypoglycemia significantly increased by 3- to 4-fold, but no difference was found between the 2 treatments in the percent of time-below-range at 6 months. Baseline HbA1c correlated with improved glucose control with U-500.

In a multivariate analysis, the researchers found that diabetic nephropathy significantly reduced the likelihood of responding to U-500 insulin (odds ratio, 0.09; 95% CI, 0.01-0.80; P <.05).

Limitations of this study included its retrospective design as well as the lack of long-term data concerning the use of other anti-hyperglycemic agents, including glucagon-like peptide-1 (GLP-1) receptor analogues. Additionally, 25% of patients were found to have stopped using U-500 during follow-up.

 “Use of concentrated insulin in pumps may represent an advance in the strategy for treating [T2DM] insulin resistant states with uncontrolled hyperglycemia after a switch from multiple daily injections to pump therapy,” the researchers concluded.

Disclosure: Multiple authors declared affiliations with the pharmaceutical industry. Please see the original article for a full list of authors’ disclosures.


Deberles E, Morello R, Hardouin J, et al. The switch from rapid-acting to concentrated regular insulin improves glucose control in type 2 diabetes patients on pump therapy: a cohort survey. Diabetes Metab. Published online October 30, 2021. doi:10.1016/j.diabet.2021.101300