Comparison of Two Treatment Regimens in Patients With Type 2 Diabetes After Short-term Intensive Insulin Therapy (SWITCH)

A 26-Week, Multi-Center, Open-label, Randomized, Parallel-group Study to Evaluate the Efficacy and Safety of Two Treatment Regimens in Patients With Type 2 Diabetes After Short-Term Intensive Insulin Therapy: Basal Insulin Based Treatment (With Prandial OADs Combination) Versus Twice-daily Premixed Insulin

Primary Objective:

To test the hypothesis that basal insulin based treatment (G+) is noninferior to twice-daily premixed insulin (PM-2) in term of hemoglobin A1c (glycosylated hemoglobin, HbA1c) reduction from baseline to end of study. The test for superiority can be done if noninferiority is achieved.

Secondary Objectives:

• To assess efficacy in terms of percentage of patients achieving HbA1c <7% and HbA1c <7% without hypoglycemia.
• To assess efficacy in terms of percentage of patients achieving fasting plasma glucose (FPG) <7 mmol/L and FPG <7 mmol/L without hypoglycemia.
• To assess safety in term of occurrence of moderate/severe hypoglycemia.
• To assess daily blood glucose (BG) variation.
• To assess patient satisfaction.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Acarbose; Drug: INSULIN GLARGINE (HOE901); Drug: Insulin Glulisine; Drug: Repaglinide; Drug: Biphasic insulin aspart 30; Drug: Metformin

Detailed Description

The duration of study is approximately 21 months. Each patient will be followed for approximately 27 weeks from screening visit to end-of-study

• Study Type: Interventional
• Enrollment (Actual): 384
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • China, China
    • China

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria :

• Patients with age between 18 and 70 years.
• Hemoglobin A1c>7.5%, and ≤11%.
• Fasting plasma glucose >7 mmol/L.
• Fasting C peptide >1 ng/mL.
• Type 2 diabetes (T2DM) patients with diabetes diagnosis between 2 and 10 years (World Health Organization 1999 T2DM diagnose criteria).
• Continuous treatment with stable doses of metformin (≥1 g/day) and 1 oral antihyperglycemic drug (at least half maximum dose) for more than 3 months prior to screening.
• Body mass index ≥21 kg/m2, and <40 kg/m2.

Exclusion criteria:

• More than 7 consecutive days of insulin treatment within the 12 months except for acute disease or surgery.
• Diabetes other than T2DM (e.g. type 1 diabetes, diabetes secondary to pancreatic disorders, drug or chemical agent intake).
• History of hypoglycemia unawareness or recurrent hypoglycemia or severe hypoglycemia within the past 12 months.
• History of sensitivity to the study drugs or to drugs with a similar chemical structure.
• Pregnancy or planned pregnancy or current lactation (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraception method).
• Acute diabetic complications (diabetic ketoacidosis, lactic acidosis, hyperosmolar nonketotic diabetic coma) within the past 12 months.
• Significant diabetic complications and serious disease, e.g., symptomatic autonomic neuropathy, gastroparesis, unstable angina or active proliferative retinopathy.
• Acute infections which may affect BG control within the past 4 weeks.
• Active liver disease, alanine transaminase (ALT) and/or aspartate aminotransferase (AST) greater than two times the upper limit of the reference range at screening.
• Impaired renal function, defined as but not limited to, serum creatinine levels ≥1.5 mg/dL (132 μmol/L) for males and ≥1.4 mg/dL (123 μmol/L) for females or presence of macroproteinuria (>2 g/day).

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Glargine based therapy; Once daily glargine plus prandial oral anti-hyperglycemic drugs	Drug: Acarbose; Pharmaceutical form: tablet Route of administration: oral administration; Other Names: Glucobay; Drug: INSULIN GLARGINE (HOE901); Pharmaceutical form: solution for injection Route of administration: subcutaneous injection; Other Names: Lantus; Drug: Insulin Glulisine; Pharmaceutical form: solution for injection Route of administration: subcutaneous injection; Other Names: Apidra; Drug: Repaglinide; Pharmaceutical form: tablet Route of administration: oral administration; Other Names: NovoNorm
ACTIVE_COMPARATOR: Premixed insulin; Twice daily premixed insulin	Drug: Biphasic insulin aspart 30; Pharmaceutical form: solution for injection Route of administration: subcutaneous injection; Other Names: Novolog Mix70/30; Drug: Metformin; Pharmaceutical form: tablet or capsule Route of administration: oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in hemoglobin A1c (HbA1c)	Change in HbA1c from baseline to week 24	Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients with fasting plasma glucose (FPG) <6.1 mmol/L	Percentage of patients with FPG <6.1 mmol/L at week 12 and week 24	At Week 12 and Week 24
Patients with FPG <6.1 mmol/L without hypoglycemia	Percentage of patients with FPG <6.1 mmol/L without hypoglycemia at week 12 and week 24	At Week 12 and Week 24
Patients with FPG <7 mmol/L	Percentage of patients with FPG <7 mmol/L at week 12 and week 2	At Week 12 and Week 24
Patients with FPG <7 mmol/L without hypoglycemia	Percentage of patients with FPG <7 mmol/L without hypoglycemia at week 12 and week 24	At Week 12 and Week 24
Patients with HbA1c <7%	Percentage of patients with HbA1c <7% at week 12 and week 24	At Week 12 and Week 24
Patients with HbA1c <7% without hypoglycemia	Percentage of patients with HbA1c <7% without hypoglycemia at week 12 and week 24	At Week 12 and Week 24
Hypoglycemic events	Incidence of hypoglycemia during treatment period	Baseline to Week 24
Change in FPG	Change in FPG from baseline to week 24	Baseline to Week 24
Change in body weight	Change in body weight from baseline to week 24	Baseline to Week 24
Insulin dose	Total daily insulin dose at week 24	At Week 24
Daily BG variation at week 24	Daily blood glucose (BG) variation at week 24	At Week 24
European quality of life - 5 dimensions (EQ-5D)	Change in quality of life scores from baseline to week 24 on 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is measured at 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problem.	Baseline to Week 24
Subgroup analysis	Subgroup analysis of control rate of HbA1c <7% according to duration of diabetes, oral anti-hyperglycemic drug(OAD) treatment and HbA1c at screening, FPG, post prandial glucose(PPG) excursion and C peptide at the beginning of run-in period, insulin dose at end of run-in period	At week 24

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Liu J, Jiang X, Xu B, Wang G, Cui N, Zhang X, Liu J, Mu Y, Guo L. Efficacy and Safety of Basal Insulin-Based Treatment Versus Twice-Daily Premixed Insulin After Short-Term Intensive Insulin Therapy in Patients with Type 2 Diabetes Mellitus in China: Study Protocol for a Randomized Controlled Trial (BEYOND V). Adv Ther. 2020 Apr;37(4):1675-1687. doi: 10.1007/s12325-020-01265-6. Epub 2020 Mar 4.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 20, 2018
• Primary Completion (ACTUAL): June 29, 2020
• Study Completion (ACTUAL): June 29, 2020

Study Registration Dates

• First Submitted: November 21, 2017
• First Submitted That Met QC Criteria: November 30, 2017
• First Posted (ACTUAL): December 2, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 25, 2022
• Last Update Submitted That Met QC Criteria: April 21, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• 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; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Insulin; Insulin, Globin Zinc; Insulin Aspart; Metformin; Insulin Glargine; Insulin glulisine; Acarbose; Biphasic Insulins; Insulin aspart, insulin aspart protamine drug combination 30:70; Repaglinide
• Other Study ID Numbers: LANTUL07194; U1111-1186-3400 (OTHER: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No