Efficacy and Safety of Saxagliptin VS. Glimepiride in Chinese T2DM Patients Controlled Inadequately With Metformin (SPECIFY)

Efficacy and Safety of Saxagliptin and Glimepiride in Chinese Patients With Type 2 Diabetes Controlled Inadequately With Metformin Monotherapy (SPECIFY Study) : a 48-week, Multi-center, Randomized, Open-label Trial

This is a multi-centre, open-label, randomized, parallel trial to investigate the efficacy and safety profile of saxagliptin and glimepiride treatment in patients with type 2 diabetes inadequately controlled with metformin monotherapy.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Saxagliptin; Drug: Glimepiride

Detailed Description

This is a multi-centre, open-label, randomized, parallel trial to investigate the efficacy and safety profile of saxagliptin and glimepiride treatment in patients with type 2 diabetes inadequately controlled with metformin monotherapy.

Screening will be made to select eligible participants before intervention. The trial will include 1-week run-in period of stable doses of metformin (1500mg) and 48-week treatment period. After the run-in period, patients were randomly assigned to one of two groups for antihyperglycaemic therapies for a total of 48-weeks: saxagliptin and glimepiride. The treatment of saxagliptin will be initiated and maintained at 5mg every morning until the completion of the study. Glimepiride will be initially treated with 1 mg every morning, and further titrated up at 4-week intervals until to reach the target fasting blood glucose (FPG).As to Glimepiride groups, if the fasting blood glucose dose not achieved the target after the maximal doses, maintain the maximal doses(6mg per day) until the completion of the study.Meanwhile, participants in both groups should take metformin 1500mg per day throughout the whole 48 weeks. At the end of the study, data will be collected and analyzed.

• Study Type: Interventional
• Enrollment (Actual): 388
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • at Division of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• For inclusion in the study subjects should fulfill the following criteria:
• Provision of informed consent prior to any study specific procedures
• Type2 diabetic patients had been on stable, maximum tolerated doses of metformin (≧1500mg/d, ≧8 weeks)
• Male or female age ≧ 25 years and ≦75 years old
• HbA1c ≧7.0 and ≦9.5%
• BMI ≧ 20 and ≦ 30 kg/m2

Exclusion Criteria:

• Subjects should not enter the study if any of the following exclusion criteria are fulfilled:
• Known or suspected allergy to trial products or related products.
• Impaired renal function defined as serum-creatinine ≥ 1.5 mg/dL (≥ 132.6 μmol/l).
• Acute or chronic disease which may cause tissue hypoxia such as cardiac or respiratory failure, shock.
• Hepatic insufficiency, acute alcohol intoxication, alcoholism.
• Subjects has a clinically significant, active (or over the past 12 months) cardiovascular history (including a history of myocardial infarction (MI), arrhythmias or conduction delays on ECG, unstable angina, or decompensated heart failure (New York Heart Association-class Ⅲ and Ⅳ).
• Proliferative retinopathy or muscular oedema requiring acute treatment.
• Lactation.
• Pregnant or positive pregnancy test at screening, nursing mother, or unwillingness to use adequate contraception (adequate contraceptive measures are sterilization, intrauterine device, oral contraceptives or barrier methods).
• Treatment with systemic corticosteroids within the past two months prior to screening.
• Tested positive for glutamic acid decarboxylase antibody.
• Receipt of any investigational drug within 1 month prior to this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Saxagliptin; The treatment of saxagliptin will be initiated and maintained at 5mg every morning until the completion of the test.Meanwhile,subjects will be instructed to take stable doses of metformin (1500mg/d) through the whole trial.	Drug: Saxagliptin; 5 mg/d; Other Names: Onglyza，Astrazeneca; Drug: Glimepiride; 1mg/d, up titrated 1mg if FPG >6.1 mmol/L (110mg/dL) till 6 mg; Other Names: Amaryl，Sanofi-Aventis
Active Comparator: Glimepiride; Glimepiride will be initially treated with 1 mg every morning to a dose of 6 mg/day.a.m. Every 4-week the subjects will be evaluated whether reach the target fasting plasma glucose (assayed by finger-stick ≦6.1 mmol/l ). If the fasting blood glucose not achieved the target at the maximum dose, maintain the maximum dose(6mg/d) until the completion of the test.Meanwhile,subjects will be instructed to take stable doses of metformin (1500mg/d) through the whole trial.	Drug: Saxagliptin; 5 mg/d; Other Names: Onglyza，Astrazeneca; Drug: Glimepiride; 1mg/d, up titrated 1mg if FPG >6.1 mmol/L (110mg/dL) till 6 mg; Other Names: Amaryl，Sanofi-Aventis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects achieving glycemic response defined as Glycosylated hemoglobin (HbA1c) < 7.0%	Compare the proportion of subjects after 48-week treatment achieving HbA1c<7.0%, with no hypoglycemia and no body weight gain (defined as glucose < 3.9 mmol/L with or without symptoms and weight gain < 3.0%).	Change from Baseline after 48 weeks treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in blood glucose fluctuations of subjects.	30 subjects of each group would be randomly chosen to evaluate blood glucose fluctuations by continuous glucose monitoring system (CGMS) before and after 48 weeks treatment.	Change from Baseline after 48 weeks treatment
The improvement in beta-cell function of subjects	All subjects would be tested in fasting proinsulin, proinsulin/insulin ratio, true insulin and C-peptide during standard meal test (75-gram instant noodles) before and after 48 weeks treatment.	Change from Baseline after 48 weeks treatment
The change in body composition of subjects.	All subjects would be measured by their weight (WT), body mass index (BMI) and waist-hip ratio (WHR) every four weeks until the end of 48 weeks treatment.	Change from Baseline after 48 weeks treatment
Safety and tolerability of saxagliptin vs. glimepiride measured by adverse events, serious adverse events (SAEs); laboratory assessments (biochemistry, lipids, blood and urine routine tests	The proportion of AEs and SAEs would be measured.Incidence of hypoglycemia episodes (defined as symptoms with glucose < 3.1 mmol/L);adverse events (AEs);serious adverse events (SAEs);laboratory assessments (biochemistry, lipids, blood and urine routine tests);other safety and tolerability parameters (ECG, vital signs, physical examination).	Change from Baseline after 48 weeks treatment

Collaborators and Investigators

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Collaborators: The First Affiliated Hospital with Nanjing Medical University; The First Affiliated Hospital of Anhui Medical University; The First Affiliated Hospital of Soochow University; Zhongda Hospital; Wuxi People's Hospital; Nanjing PLA General Hospital; Changzhou No.2 People's Hospital; Huai'an First People's Hospital
• Investigators: Principal Investigator: Dalong Zhu, MD, PhD, The Affiliated Drum Tower Hospital of Nanjing University

Publications and helpful links

General Publications

• Gu T, Ma J, Zhang Q, Zhu L, Zhang H, Xu L, Cheng J, Shi B, Li D, Shao J, Sun Z, Zhong S, Bi Y, Zhu D. Comparative effect of saxagliptin and glimepiride with a composite endpoint of adequate glycaemic control without hypoglycaemia and without weight gain in patients uncontrolled with metformin therapy: Results from the SPECIFY study, a 48-week, multi-centre, randomized, controlled trial. Diabetes Obes Metab. 2019 Apr;21(4):939-948. doi: 10.1111/dom.13605. Epub 2019 Jan 4.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: October 23, 2014
• First Submitted That Met QC Criteria: October 30, 2014
• First Posted (Estimate): October 31, 2014

Study Record Updates

• Last Update Posted (Actual): July 23, 2018
• Last Update Submitted That Met QC Criteria: July 19, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: saxagliptin; glimepiride; metformin monotherapy
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Glimepiride; Saxagliptin
• Other Study ID Numbers: ISSSAXA0014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED