Switch From Rapid-Acting to Concentrated Insulin Improves Glycemic Control

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 ((HbA_1c), 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 HbA_1c was 9.03±1.58.

After patients switched to U-500, mean HbA_1c 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 HbA_1c 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 HbA_1c 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.

Reference

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