Introduction

Premixed insulin is used widely due to its convenience for managing both basal and prandial glucose. Although the premix insulin simplifies the dosing regimen, its use is associated with reduced flexibility in managing glucose levels, resulting in sub-optimal glycemic control. Patients treated with premixed insulin often experience substantial fluctuations in blood glucose levels, putting them at an increased risk of complications. Vildagliptin, a dipeptidyl peptidase (DPP)-4 inhibitor has good safety and efficacy profile with a relatively low risk of hypoglycemic events. The safety and efficacy of vildagliptin in combination with premix insulins has not been evaluated completely till date.

Aim

To determine the impact of vildagliptin on the glycemic variability in patients being treated with premixed insulins.

Patient Profile

• Patients with type 2 diabetes mellitus (T2DM), with poor glycemic control while on premixed insulin therapy and on a single drug or a combination of oral hypoglycemic medications for more than two months.
• The study subjects had no acute complications associated with diabetes (ketoacidosis, hyperosmolar disease).
• Following patients were excluded: Patients who had taken GLP-1agonists within last 3 month, those with insulin allergies, with alanine transaminase (ALT) 2.5 times higher than the upper limit of normal, and serum creatinine level 1.3 times higher than the upper limit of normal, those with impaired liver and renal function, having a history of alcohol abuse, or having other severe health conditions like heart disease, lung disease or neurological disease etc.
• Vildagliptin was added subsequently to the treatment regimen of the patients in the treatment group.

Methods

Study Design

• A secondary analysis of a premix insulin study.

Treatment Strategy

• Treatment group: Patients received vildagliptin in addition to the premixed insulin therapy (n=22).
• Control group: Patients had their insulin doses adjusted without adding vildagliptin (n=22).

Assessments

• Patients underwent flash glucose monitoring (FGM) for 14 days at the beginning of the study and at 3 months after the study initiation.
• Other assessments included C-peptide, glycosylated hemoglobin (HbA1c), glycated albumin (GA), and insulin measurement.
• Body mass index (BMI) was calculated for all the individuals.

Outcomes

• Blood glucose changes before and after the treatment.

Results

• Patients in both the study groups had significant decrease in HbA1c levels at 3 months. Patients in the vildagliptin group had a significantly greater decrease in the GA levels, as compared to control group (Table 1).

Table 1: Change in blood parameters during the study

• Patients in the vildagliptin group had prominent reductions in mean blood glucose and substantial reduction in the mean amplitude of glycemic excursion, as compared to the control group (Table 2).
• The time above the target range (TAR) reduced significantly after vildagliptin treatment, as compared to before treatment. Vildagliptin treatment was associated with significant increases in time in the target range (TIR), time below the target range (TBR), Area Under the Curve (AUC) >4.4 and AUC >3.9, as compared to before treatment with vildagliptin (Table 2).
• Additionally at the end of the treatment, patients in the vildagliptin group had significantly lower MBG, MAGE, and TAR, and a significantly increased TIR, as compared to the control group (Table 2).

Table 2: Changes in the blood glucose excursion parameters during the study

• The daily insulin dose was significantly reduced in vildagliptin treated patients (40.45 36.68, P=0,050) but not in control group (37.09 vs. 30.45, P=0.603) when comparing before and after treatment insulin daily doses.
• Vildagliptin significantly reduced the hourly mean blood glucose during the second FGM (after 3 months of treatment), as compared to FGM at baseline (P=0.001). Patients in the vildagliptin group had lower blood glucose levels, over a 2-week period, particularly after dinner (P=0.022) as indicated by hourly mean blood glucose levels.

Conclusions

• Addition of vildagliptin to premixed insulin effectively reduced blood glucose levels and reduced glycemic variability in patients with T2DM.
• Nevertheless, clinicians should be cautious about the potential hypoglycemia associated with vildagliptin.

Front. Endocrinol. June 2025;16:1508918. doi: 10.3389/fendo.2025.1508918.