Comparison of Standard vs Higher Starting Dose of Insulin Glargine in Chinese Patients With Type 2 Diabetes (Glargine Starting Dose)

Comparison of Efficacy and Safety of Standard vs Higher Starting Dose of Insulin Glargine in Overweight and Obese Chinese Patients With Type 2 Diabetes

Primary Objective:

-To test the hypothesis that higher initial dose of basal insulin (0.3 U/kg) is non inferior to standard initial dose (0.2 U/kg) based on the percentage of patients with at least one episode of hypoglycemia (≤3.9 mmol/L or severe) during the 16 weeks of treatment in overweight and obese type 2 diabetic patients uncontrolled with oral anti-diabetes drugs (OADs).

Secondary Objective:

• To evaluate the percentage of patients achieving glycated hemoglobin (HbA1c) <7%.
• To evaluate the percentage and accumulated percentage of patients achieving fasting plasma glucose (FPG) target (<5.6, <6.1, and <7.0 mmol/L).
• To assess the changes in HbA1c, FPG, and postprandial glucose (PPG).
• To evaluate the insulin doses change.
• To evaluate the weight change.
• To evaluate overall hypoglycemia, nocturnal hypoglycemia and severe hypoglycemia occurrence.
• To descriptively evaluate the safety profile.
• To assess patient and physician satisfaction and adherence (drop-out rate and the percentage of patients who can follow the treatment and insulin titration).
• Subgroup analysis on efficacy (control rate, control rate without confirmed hypoglycemia, and changes in HbA1c, FPG and PPG) and safety data according to:
• Age
• Duration of diabetes
• Baseline treatment (OAD)
• Baseline HbA1c, FPG and PP

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: INSULIN GLARGINE; Drug: metformin; Drug: acarbose

Detailed Description

The duration of study for each patient is approximately 20 weeks from screening visit to end-of-study follow-up phone call.

• Study Type: Interventional
• Enrollment (Actual): 892
• Phase: Phase 4

Contacts and Locations

Study Locations

• 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 :

• Age ≥ 18 and ≤ 70 years.
• Type 2 diabetes patients with diabetes diagnosis at least 2 years.
• Continuous treatment with stable doses of 2-3 OADs, for more than three months prior to randomization, among which metformin ≥1.5 g/day or at maximum tolerated dose
• HbA1c >7.5% and ≤11%.
• FPG >9 mmol/L.
• BMI ≥25 and ≤40 kg/m^2.
• Ability and willingness to perform self-monitoring of blood glucose using the Sponsor-provided glucose meter and to complete the patient diary.
• Willingness and ability to comply with the study protocol.
• Signed informed consent obtained prior any study procedure.

Exclusion criteria:

• Known hypersensitivity/intolerance to insulin glargine or any of its excipients.
• History of hypoglycemia unawareness.
• Unexplained hypoglycemia in the past 6 months.
• 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).
• History of stroke, myocardial infarction, angina pectoris, coronary artery bypass graft, or percutaneous transluminal coronary angioplasty within the previous 12 months.
• Active proliferative retinopathy, as defined by a photocoagulation or vitrectomy occurrence in the 6 months prior to study entry, or any other unstable (rapidly progressing) retinopathy that may require photocoagulation or surgical treatment during the study, documented by retina examination or disease history record, in the 2 years prior to study entry.
• 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).
• Active liver disease (alanine transaminase [ALT] greater than two times the upper limit of the reference range, as defined by the local laboratory).

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 Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard initial dose of insulin glargine; Dose 1 of insulin glargine will be administered subcutaneously once a day at the same time every day. Previous non-sulfonylurea OADs (eg, metformin, acarbose) are background treatment and will be continued at the same dosage and dosing frequency as before.	Drug: INSULIN GLARGINE; Pharmaceutical form: solution Route of administration: subcutaneous injection; Other Names: HOE901; Drug: metformin; Pharmaceutical form: table or capsule Route of administration: oral administration; Drug: acarbose; Pharmaceutical form: table or capsule Route of administration: oral administration
Experimental: Higher initial dose of insulin glargine; Dose 2 of insulin glargine will be administered subcutaneously once a day at the same time every day. Previous non-sulfonylurea OADs (eg, metformin, acarbose) are background treatment and will be continued at the same dosage and dosing frequency as before.	Drug: INSULIN GLARGINE; Pharmaceutical form: solution Route of administration: subcutaneous injection; Other Names: HOE901; Drug: metformin; Pharmaceutical form: table or capsule Route of administration: oral administration; Drug: acarbose; Pharmaceutical form: table or capsule Route of administration: oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients with at least one episode of hypoglycemia	16 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients achieving HbA1c <7%	16 weeks
Percentage of patients achieving Fasting Plasma Glucose target (<5.6, <6.1, and <7.0 mmol/L)	16 weeks
Accumulated percentage of patients achieving Fasting Plasma Glucose target (<5.6, <6.1, and <7.0 mmol/L)	16 weeks
Change from baseline in HbA1c	Baseline, 16 weeks
Change from baseline in Fasting Plasma Glucose	Baseline, 16 weeks
Change from baseline in Post Prandial Glucose	Baseline, 16 weeks
Change in body weight	Baseline, 16 weeks
- Change in insulin dose	Baseline, 16 weeks
Number of overall hypoglycemic events (with severe or confirmed hypoglycemia [≤3.9 mmol/L])	Baseline, 16 weeks
Number of nocturnal hypoglycemic events	Baseline, 16 weeks
Number of severe hypoglycemic events	Baseline, 16 weeks

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Wan H, Wen B, Wang X, Wang J, Zhang Y, Ning T, Duan B, Li Y, Feng W, Zhang X, Cui N, Ji L. Effect of Baseline Characteristics on Hypoglycaemia Risk with Insulin Glargine 100 U/mL: Post Hoc Analysis of the BEYOND 7 Study. Diabetes Ther. 2021 Sep;12(9):2359-2369. doi: 10.1007/s13300-021-01112-z. Epub 2021 Jul 21.
• Ji L, Gao Z, Shi B, Bian R, Yin F, Pang W, Gao H, Cui N. Safety and Efficacy of High Versus Standard Starting Doses of Insulin Glargine in Overweight and Obese Chinese Individuals with Type 2 Diabetes Mellitus Inadequately Controlled on Oral Antidiabetic Medications (Beyond VII): Study Protocol for a Randomized Controlled Trial. Adv Ther. 2018 Jun;35(6):864-874. doi: 10.1007/s12325-018-0717-x. Epub 2018 Jun 5.

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2016
• Primary Completion (Actual): April 26, 2018
• Study Completion (Actual): April 26, 2018

Study Registration Dates

• First Submitted: July 7, 2016
• First Submitted That Met QC Criteria: July 14, 2016
• First Posted (Estimate): July 19, 2016

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; Metformin; Insulin Glargine; Acarbose
• Other Study ID Numbers: LANTUL07191; U1111-1172-2903 (Other Identifier: 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