Background
Diabetes mellitus is associated with a two to three-fold increase in risk of cardiovascular disease. However, intensive glucose-lowering therapy aiming at reducing HbA1c to a near-normal level failed to suppress cardiovascular events in recent randomized controlled trials. Glycosylated Hemoglobin (HbA1c) reflects average glucose level rather than glycemic variability. Glycemic variability has been shown to be associated with greater reactive oxygen species production and vascular damage, compared to chronic hyperglycemia. These findings suggest that management of glycemic variability plays an important role in diabetes management.

Aim
The aim of this study to determine daily glycemic excursions by Continuous Glucose Monitoring (CGMS) in type 2 diabetic patients receiving Voglibose as Add-On Therapy in India.

Method
50 type 2 diabetes mellitus (T2DM) patients were recruited from our diabetes center in southern India. The inclusion criteria was age 18-70 years, BMI, ≥ 23 kg/m2, HbA1c, ≥ 7% (for at least 3 months prior screening) on stable dose of Metformin only or a combination of Metformin and Sulfonylurea. Patients with at least 2 postprandial glucose (within 2 hours of meal) excursions above 140 mg/dl within the 14 day period of the Freestyle Libre Pro were enrolled for the study. HbA1c, Lipid profile, fasting plasma glucose (FPG), and post-prandial plasma glucose (PPG) were done during the screening. During visit 2, Voglibose was added to the existing therapy and the Freestyle Libre Pro was applied. Similarly at, visit 4, i.e 3rd month of Voglibose therapy, Freestyle Libre Pro was applied to measure the Mean Amplitude of Glycemic Excursion (MAGE).

Results
The mean age of the study population was 51±9 years and 54% were males. After 3 months of treatment with Voglibose, HbA1c reduced from 8.75±1.50% to 7.61±1.04% (p<0.0001). Similarly FPG reduced from 175±55mg/dl to 145±36 mg/dl (p<0.0001); PPG reduced from 275±79 mg/dl to 226±72 mg/dl (p<0.0001) and MAGE reduced from 162±42 mg/dl to 146±32 mg/dl (p=0.005). Reduction in the FPG (p=0.0002), PPG (p=0.0002) and MAGE (p<.0001) values became statistically significant, even within 14 days of initiating voglibose therapy.
 
Comparison of glycemic variability and biochemical parameters between Screening (V1) and Intervention (V4- 3 months after voglibose treatment)
 
VARIABLES	                                           Visit 1 (n=50)	   Visit 4 (n=50)	 P Value
			
Age(years)	                                             0.62±9.30	                     -	                        -
Male, n (%)	                                             27(54.00%)	             -	                        -
BMI (kg/m2)	                                             28.60±4.28	       28.2±4.3	           0.004
Pulse rate (bpm)	                                     77.42±8.36	     77.80±5.88	   0.7826
Systolic Blood Pressure (mmHg)	     126.14±13.31	    121.96±11.55	   0.021
Diastolic Blood Pressure (mmHg)	     79.46±7.20	     75.72±7.32	   0.0004
Temperature (F)	                                      98.56±0.10	     98.56±0.08	   0.8962
Respiratory rate (R/min)	                      18.68±3.09	     19.54±2.62	   0.0236
Serum HbA1c (%) (from Lab)	               8.75±1.50	     7.61±1.04	          <.0001
Fasting blood glucose(mg/dl)	              175.28±55.17	     144.50±35.54	  <.0.0001
Post-prandial blood glucose(mg/dl)      275.10±78.90     226.36±72.41	  <.0.0001
HbA1c level estimated by AGP* (%)      7.23 ±1.48	     6.72 ±1.10	     0.0109
MAGE (average number of 
glycemic excursions)	                              161.9±42.0	     146.3±31.7	     0.0057
Time in targeted glucose levels (%)	       37.7±22.8	     46.9±21.1	             0.0019
Time below target glucose levels (%)	4.4±9.8	              4.9±7.2	            0.7958
Time above target glucose levels (%)	57.9±30.0	     47.7±25.3	            0.0115


Discussion
This study shows the effect of Voglibose in reducing the glycemic variability in type 2 diabetes patients. The reduction in glycemic variation is seen within 14 days of initiating voglibose therapy and it was seen upto 3 months. As minimizing glycemic variability is considered to be an important aspect of glucose management, adding Voglibose in type 2 diabetic patients could be a useful addition.

Comparison of glycemic excursion in patients with type 2 DM after treatment with Voglibose by continuous glucose monitoring device