Vildagliptin and Sitagliptin both belong to the class of DPP-4 inhibitors, but differ in their pharmacokinetic profile as well as in their approved application (Vildagliptin, 2x 50 mg daily, Sitagliptin, 1x 100 mg daily). This leads to distinct results regarding postprandial blood-glucose normalization as well as protective properties regarding hypoglycemic episodes - especially during the night. Additionally, in type 1 diabetic patients a correlation has been described between hypoglycemia and abnormal heart function (QTc-elongation), which can have severe consequences for the patients. This study aims for the evaluation of the potency of both drugs to prevent and/or reduce hypoglycemic events in insulin-dependent type-2 diabetics and furthermore to evaluate the correlation of hypoglycemic episodes with changes in heart-function measured by Holter-ECG. The hypothesis is tested, if vildagliptin leads to a more favourable glycemic profile than sitagliptin and is more potent in protecting from nocturnal abnormalities in heart-function caused by undetected hypoglycemic episodes.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
51
vildagliptin 50mg BID for 8 weeks
sitagliptin 100mg QD for 8 weeks
Novartis Investigative Site
Berlin, Germany
Novartis Investigative Site
Berlin, Germany
Novartis Investigative Site
Dortmund, Germany
Novartis Investigative Site
Dresden, Germany
Novartis Investigative Site
Elsterwerda, Germany
Novartis Investigative Site
Falkensee, Germany
Novartis Investigative Site
Magdeburg, Germany
Novartis Investigative Site
Neuss, Germany
Novartis Investigative Site
Potsdam, Germany
Novartis Investigative Site
Sulzbach-Rosenberg, Germany
...and 1 more locations
Hypoglycemic Profile of Vildagliptin Compared to Sitagliptin Over 4 Days After 8 Weeks of Treatment in Period 1 & 2
The hypoglycemic profile is defined as the area under the curve glucose-time profile obtained by continuous glucose monitoring Interstitial glucose values below 3.9 mmol/L (averaged over 5 minutes) were considered relevant for the estimation of the interstitial glucose AUC in the hypoglycemic range These AUC\<3.9mmol/L/5min. values were summed up over 4 days (unit: mmol/L/4d) or over 24 hours at measurement Days 2, 3, 4, and 5 (unit: mmol/L/24h). Lower values for AUC reflect less intense hypoglycemia.
Time frame: baseline and 0-24 hours post-dose on Days 2 to 5
Number of Hypoglycemic Events During Vildagliptin Treatment Compared to Sitagliptin Treatment.
Hypoglycemic events are defined as blood glucose values \<70 mg/dL measured by a self-monitored blood glucose (SMBG) or continuous glucose monitoring (CGM) measurement regardless of any symptoms suggestive of low blood glucose.
Time frame: after 8 weeks period 1 and Period 2
Mean Duration of Hypoglycemic Events (Min.) Measured With Continuous Glucose Monitoring (CGM) Over 4 Days After 8 Weeks of Treatment for Period 1 & Period 2
the mean duration of hypoglycemic events is detected by continuous glucose monitoring (CGM)measurement.
Time frame: after 8 weeks for Period 1 & Period 2
Mean Amplitudes of Hypoglycemic Events (mmol/L) Measured With Continuous Glucose Monitoring (CGM) Over 4 Days After 8 Weeks of Treatment for Period 1 & Period 2
To evaluate by CGM measurement the grade of severity of hypoglycemia measured as the mean amplitude over 4 days after 8 weeks of treatment in Period 1 \& Period 2
Time frame: after 8 weeks Period 1 & Period 2
Number of Severe Hypoglycemic Events During Vildagliptin Treatment Compared to Sitagliptin Treatment After 8 Weeks of Treatment in Period 1 and Period 2
Severe hypoglycemic events are defined as any episode requiring the assistance of another party or measured plasma glucose levels of \<40 mg /dL. Assessed by self-monitored blood glucose (SMBG)After 8 weeks of treatment in Period 1 and Period 2
Time frame: after 8 weeks Period 1 & Period 2
Glucose Fluctuations During the Day Under Vildagliptin Treatment Compared to Sitagliptin Treatment on Day 2 After 8 Weeks of Treatment Period 1 & Period 2
Glucose fluctuations are assessed by the mean amplitude of glycemic excursions (MAGE) and standard deviations (SD) (Service et al., 1970). on day 2 after 8 weeks of treatment Period 1 \& Period 2
Time frame: Day 2 after 8 weeks of treatment Period 1 & Period 2
Number of Participants With ECG Abnormalities Depending on Hypoglycemic Events After 8 Weeks of Treatment Period 1 & Period 2
ECG abnormalities are defined as either: • Occurrence of \>30 ventricular extrasystoles (VES) per hour or • Occurrence of ≥2 consecutive VES (Couplets) or • Occurrence of ≥3 consecutive VES (Triplets) or • QT-time corrected for heart rate (QTc) \>440 ms. after 8 weeks of treatment Period 1 \& Period 2
Time frame: after 8 weeks of treatment Period 1 & Period 2
Change From Baseline of Inflammatory Biomarkers High Sensitivity C-reactive Protein (hsCRP) After 8 Weeks of Treatment in Period 1 & Period 2
The inflammatory biomarkers hsCRP was assessed at baseline and after 8 weeks of treatment Period 1 \& Period 2
Time frame: Baseline, after 8 weeks Period 1 & Period 2
Change From Baseline of Inflammatory Biomarkers Interleukin 6 (IL-6) After 8 Weeks of Treatment in Period 1 & Period 2
The inflammatory biomarkers IL-6 was assessed at baseline and after 8 weeks of treatment Period 1 \& Period 2
Time frame: Baseline, after 8 weeks Period 1 & Period 2
Percentage Change From Baseline of Pro-insulin/C-peptide Ratios After 8 Weeks of Treatment Period 1 & Period 2
Percentage Change from baseline of pro-insulin/C-peptide ratios after 8 weeks of treatment Period 1 \& Period 2 Higher pro-insulin / C-peptide ratios (expressing disproportional hyperproinsulinemia) may be associated with increasing beta cell dysfunction and more inefficient pro-insulin processing
Time frame: Baseline, after 8 weeks Period 1 & Period 2
Number of Occurrence of Pre-defined ECG Findings During 4 Days of Continuous ECG Monitoring at Baseline and in the 8th Week of Periods 1 and 2
Number of Occurrence of pre-defined ECG findings during 4 days of continuous ECG monitoring at baseline and in the 8th week of Periods 1 and 2. ECG data were continuously recorded and analyzed over a period of 4 days simultaneously with continuous glucose monitoring. It assessed number of any Vertical Electric(al) Sounding (VES), number of 2 consecutive VES \[couplets\], and number of \>3 consecutive VES \[salves\]
Time frame: after 8 weeks Period 1 & Period 2
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