Deintensification of basal-bolus insulin therapy by switching to a fixed-ratio combination of insulin glargine and lixisenatide in patients with type 2 diabetes

BACKGROUND: Deintensification of basal-bolus insulin therapy (BBIT) with simplification of the treatment regimen is a possible and necessary therapeutic strategy for some patients with type 2 diabetes (T2D). One of the options for deintensification is the transition to fixed combination of insulin glargine/lixisenatide (iGlarLixi).

AIM: To determine the efficacy and safety of deintensification of BBIT in hospitalized patients with T2D by switching to iGlarLixi under continuous glucose monitoring (CGM).

MATERIALS AND METHODS: Design: single-center, comparative, observational study in real-world settings. A total of 283 T2D patients on BBIT were included, 118 subjects underwent BBIT deintensification under CGM control according to clinical indications, 165 patients continued BBIT. Thirty patients were re-examined one year after deintensification. Time In target Range (TIR), Time Above Range (TAR), Time Below Range (TBR), as well as Coefficient of Variation (CV), Mean Amplitude of Glycemic Excursions (MAGE), Lability Index (LI), and Mean Absolute Glucose rate of change (MAG) were estimated. Endogenous insulin secretion was assessed by fasting and 2-hour postprandial C-peptide levels. The estimated glucose disposal rate (eGDR) was used as a measure of insulin sensitivity.

RESULTS: The groups were similar in age, diabetes duration, glycated hemoglobin (HbA1c) and eGDR. Body mass index (BMI) and C-peptide levels were higher, while the duration of insulin therapy and initial daily insulin dose (DID) were lower in patients of the deintensification group (all p<0.0004). During deintensification, DID was reduced (from 64 to 30 U/day, p<0.001). The achieved TIR and TBR values did not differ in two groups. In patients on iGlarLixi, TAR L2 (>13.9 mmol/L), CV, MAGE and MAG were lower (all p<0.05). In multivariate regression analysis, BMI, DID and fasting C-peptide were associated with successful deintensification. In ROC analysis, fasting C-peptide was the best predictor with a cut-off point of 0.92 ng/mL. One year after the treatment deintensification, there was a decrease in HbA1c (-0.5%, p=0.001) and body weight (-0.8 kg, p=0.003) and an increase in postprandial C-peptide levels (p=0.029) without changes in eGDR.

CONCLUSION: Switching to iGlarLixie is an effective therapeutic option for patients with T2D with normal C-peptide levels who require deintensification of BBIT.

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