The Effect of Soliqua on Glucose Variability in Type 2 Patients Among South Asians

NCT ID: NCT03819790

Last Updated: 2021-02-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 119 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-02
• Study Completion Date: 2019-11-19

Brief Summary

The overall objective of this study is to compare the effects of Soliqua, a titratable combination of insulin and GLP-1 receptor agonist in a single pen versus Glargine U100 insulin (Basaglar or Lantus) and gliclazide MR, both added to metformin, on measures of glucose variability using masked CGM data among people of South Asian origin living in Canada with type 2 diabetes (T2DM).

Detailed Description

The VARIATION 2 SA study is a prospective, open-label, randomized controlled, multi-centre trial to compare the efficacy of two insulin initiation approaches (Soliqua vs Glargine U100 insulin (Basaglar or Lantus) + gliclazide MR) added to maximum tolerated metformin on glucose variability (using masked CGM) in South Asians with T2DM who will initiate insulin therapy with HbA1c of 7.1-11% (inclusive). After giving informed consent and being assessed by eligibility, the patient will stop other oral hypoglycemic agents except metformin (SGLT2 inhibitor may be continued if the patient has cardiovascular diseases history) and enter a 1-week run-in phase with Basaglar or Lantus insulin. During this week (considered as baseline), the patient will: 1) be administered Basaglar or Lantus insulin at an initial dose of 10 units in the morning and increase 1 U/day if fasting glucose >5.5 mmol/L; 2) complete 2 questionnaires to assess the patient-reported outcomes (PROs); 3) wear a masked continuous glucose monitor (CGM) to assess glucose variability; 4) record carbohydrate intake for at least 3 consecutive days. If a patient demonstrates good adherence to Basaglar or Lantus insulin therapy, proper CGM wearing and proper record of carbohydrate intake, and is willing to adhere to insulin treatment will be randomly assigned (1:1) to receive either Soliqua or Glargine U100 insulin (Basaglar or Lantus) + gliclazide MR treatment. The patients will initiate insulin Soliqua or Basaglar/Lantus at their end-of run-in phase insulin dose (minimum dose of 15 units in both arms) every morning (before first meal of day) and titrate by 1 U/day until fasting glucose reaches 4-5.5 mmol/L. In the next 12 weeks, the patients will be optimized their insulin doses via clinic visits or phone calls. They will also be instructed to record their daily fasting glucose, insulin dose, hypoglycemic episodes and any adverse events in a logbook. The primary outcome is to compare the difference of average percentage of Time in Range (4.0-10.0 mmol/L) within 24 hours over the CGM period between two treatments at week 13 after randomization. The co-primary is to compare the difference average percentage of Time in Range (4.0-10.0 mmol/L) within 12 hours (6 AM- 6 PM) over the CGM period between two treatments at week 13 after randomization. The secondary outcomes include the differences on other measurements of glucose variability and patient-reported outcomes (PROs).

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Insulin Glargine + GLP-1 RA

Insulin Soliqua (a titratable combination of insulin Glargine + GLP-1 RA) will be administered at the subject's end-of run-in phase insulin dose (minimum dose of 15 units in both arms) every morning (before first meal of day) and titrate by one unit per day until fasting glucose level of 4-5.5 mmol/L is obtained, with or without metformin.

Group Type: EXPERIMENTAL

Basal insulin glargine and lixisenatide

Intervention Type: DRUG

Soliqua (insulin glargine and lixisenatide): a titratable combination of long-acting basal insulin glargine and lixisenatide (Glucagon-like peptide-1 receptor agonist)

Metformin

Intervention Type: DRUG

Patients can be administered with most tolerant dose of metformin

Basaglar/Lantus + gliclazide MR

Basal insulin Basaglar/Lantus will be administered at the subject's end-of run-in phase insulin dose (minimum dose of 15 units in both arms) every morning (before first meal of day) and titrate by one unit per day until fasting glucose level of 4-5.5 mmol/L is obtained, with gliclazide MR 60 mg OD, with or without metformin.

Group Type: ACTIVE_COMPARATOR

Basal insulin Basaglar/Lantus + gliclazide MR

Intervention Type: DRUG

basal long-acting insulin Basaglar/Lantus with gliclazide MR 60 mg OD

Metformin

Intervention Type: DRUG

Patients can be administered with most tolerant dose of metformin

Interventions

Basal insulin glargine and lixisenatide

Soliqua (insulin glargine and lixisenatide): a titratable combination of long-acting basal insulin glargine and lixisenatide (Glucagon-like peptide-1 receptor agonist)

Intervention Type: DRUG

Basal insulin Basaglar/Lantus + gliclazide MR

basal long-acting insulin Basaglar/Lantus with gliclazide MR 60 mg OD

Intervention Type: DRUG

Metformin

Patients can be administered with most tolerant dose of metformin

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male and female adults with clinical diagnosis of T2DM diagnosed at least 1 year before screening and in stable health as assessed by investigator
• Age between 18 and 80 years (inclusive)
• Body mass index (BMI) between 20-40 kg/m2 (inclusive)
• South Asian origin including Afghanistani, Bangladeshi, Indian, Nepali, Pakistani and Sri Lankan. This includes those patients who identify themselves as South Asian origin because their ancestors moved from South Asian to another country (e.g. Caribbean islands, Fiji, etc.)
• A1C in range of 7.1-11% (inclusive)
• Fasting glucose on self-monitoring of blood glucose (SMBG) or laboratory testing < 15 mmol/L within the last 30 days
• Insulin naïve, uncontrolled on oral hypoglycemic medications
• Kidney function assessment with eGFR >30 mL/min/1.73 m2
• Written informed consent obtained

Exclusion Criteria

• History of insulin use (except emergency short-term use defined as less than 12 weeks for acute illness, hospitalization, pregnancy or with steroid use)
• Use of GLP-1 receptor agonist in the past 3 months
• Previous discontinuation of a GLP-1 receptor agonist due to safety, tolerability or lack of efficacy
• Pregnant or anticipating pregnancy
• Current use of steroid
• Currently on any supervised, intensive, weight-loss dietary or exercise program
• History of gastroparesis with moderate or higher severity
• History of pancreatitis
• Amylase and /or lipase more than three times the upper limit of normal or calcitonin ≥ 20 pg/mL (5.9 pmol/L)
• Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia (MEN) syndrome
• Allergic reaction to insulin secretagogues
• History of weight loss surgery (bariatric bypass surgery or gastric banding)
• Inability to check SMBG or wear CGM
• History of severe liver disease or alcohol abuse
• Severe hypoglycemic reaction (defined as third-party or ambulance assistance or emergency department visit) within the last 3 months before screening visit
• Night-shift workers
• Patients who are recommended to achieve relaxed targets of A1C up to 8.5% by Diabetes Canada 2018 clinical practice guidelines
• Current enrollment in another intervention study
• Patients who miss ≥1 injections of Basaglar/Lantus or discontinue the CGM device or can not record carbohydrate intake correctly during the run-in phase

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

LMC Diabetes & Endocrinology Ltd.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

LMC Brampton

Brampton, Ontario, Canada

LMC Etobicoke

Etobicoke, Ontario, Canada

LMC Scarborough

Toronto, Ontario, Canada

Countries

Canada

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Other Identifiers

VARIATION 2 SA

Identifier Type: -

Identifier Source: org_study_id