The baseline characteristics of the drug naïve patients with HbA1c <7.5% randomised in the VERIFY trial
J. E. Foley(1), S. Del Prato(2), M. Stumvoll(3), P. Proot(4), P.M. Paldánius(4), D. R. Matthews(5)
1Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA 
2University of Pisa, Pisa, Italy
3University Hospital Liepzig, Liepzig, Germany
4Novartis Pharma AG, Basel, Switzerland
5Oxford Centre for Diabetes, Endocrinology and Metabolism and Harris Manchester College, Oxford, United Kingdom


Background: Vildagliptin Efficacy in combination with metfoRmIn For earlY treatment of T2DM (VERIFY) is a 5-year ongoing trial exploring whether an initial combination oral antidiabetes drug (OAD) therapy of metformin-vildagliptin would provide a more durable glycaemic control compared with the standard-of-care metformin monotherapy followed by addition of vildagliptin when metformin monotherapy is no longer adequate to keep HbA1c levels below 7%. 
Aim: We report the baseline characteristics of patients included in the VERIFY study.
Methods: VERIFY is a multi-national (254 centres across 34 countries), multi-ethnic (Caucasian, Native Americans, Asian and Africans), randomised, double-blind, two-arm, parallel group study enrolling drug naïve patients aged 18−70 years, BMI 22−40 kg/m2, normal renal function, diagnosed with T2DM (≤24 months) and HbA1c levels 6.5−7.5%. Patients received standard of care medications for blood pressure and lipids. In a subset of patients standardised and locally adapted meal tests are performed. Blood samples are collected at -20 min, 0 min (start of the meal test), 15 min, 30 min, 60 min, 90 min & 120 min to assess plasma glucose, C-peptide and insulin concentrations. The integrated insulin secretion rate relative to the integrated glucose levels over 2 hours (ISR/G) in pmol/min/m2/mmol/L was calculated from glucose and C-peptide (clearance counted for by deconvolution) values and the oral glucose insulin sensitivity index (OGIS) was calculated from the glucose and insulin values.
Results: Despite predictions that it would be difficult to recruit VERIFY, 1416 patients of 4524 patients screened, were excluded because their glycaemic levels were below the inclusion criteria (HbA1c <6.6%) as opposed to only 702 patients who failed screening because their baseline HbA1c levels were above the inclusion criteria (HbA1c >7.5%). 66 patients who could not tolerate a metformin dose of 1000 mg/day were classified as run-in failures. Overall, 2001 patients from Europe (52.4%), Latin America (26.8%), Asia (17.15%), South Africa (3.1%) and Australia (0.5%) were included. Patients were newly diagnosed with a mean T2DM duration of 6.5±7.7 months and 47% of patients were men. The mean age of patients was 54.3±9.4 years and more than 25% were under the age of 50; age was about 5 years lower in India than other regions. Mean weight was 85.5±17.5 kg and baseline BMI averaged 31.1±4.7 kg/m2; mean weight and BMI were lower in Asians than other groups. About 14% of the overall patient population reported a history of smoking, ~18% in the European region as compared to ~10% in other regions. The average daily dose of metformin was approximately 1600 mg. The mean baseline glomerular filtration rate was 87.4±18.5 mL/min/1.73m2, the mean baseline HbA1c was 6.9±0.3% and the mean baseline FPG was 7.5±1.5 mmol/L; patients from Europe had relatively higher mean FPG level of ~7.9 mmol/L while those in other regions had relatively lower mean FPG levels of 7.1 mmol/L. Fasting insulin was 117±97 pmol/L, HOMA-B was 117±97 and HOMA-IR was 6.6±6.3. Mean sitting systolic blood pressure was 132.3±14.4 mmHg and sitting diastolic was 80.6±8.61 mmHg. Low density lipoprotein cholesterol, very low density lipoprotein cholesterol and triglyceride levels were 2.89±0.94 mg/dL, 0.54±0.34 mg/dL and 1.92±0.96 mg/dL respectively. Microvascular complications were reported in only ~8% of patients. In the subset of patients (n=462) who undertook meal tests the 2 hour plasma glucose values were 9.3±2.8 mmol/L, the ISR/G was 27.8±12.3 pmol/min/m2/mmol/L and the OGIS was 353±57 ml/min/m2. 
Discussion: VERIFY study population is representative of the major racial populations of the world and essentially evenly divided on the basis of sex, is truly newly diagnosed and has an age range that represents the vast majority of the patients observed to have diagnosed T2DM. The patients have normal renal function and on average are obese; the blood pressure and fasting lipid profiles, the high fasting insulin levels, and degrees of both fasting and meal associated insulin resistance are associated with such obesity. The insulin response to this increased insulin resistance is robust, but clearly not enough to prevent elevations in 2 hour glucose values during meals, in FPG  values and in HbA1c values in the mildly hyperglycemic range of T2DM  in VERIFY study population. Thus these T2DM subjects display the classic profile of inadequate insulin secretion in the face of the increased demand for insulin associated with obesity.

The baseline characteristics of the drug naïve patients with HbA1c &lt;7.5% randomised in the VERIFY trial

The baseline characteristics of the drug naïve patients with HbA1c <7.5% randomised in the VERIFY trial