Effect of Liraglutide or Glimepiride Added to Metformin on Blood Glucose Control in Subjects With Type 2 Diabetes

Effect of Liraglutide or Glimepiride Added to Metformin on Glycaemic Control in Subjects With Type 2 Diabetes

This trial is conducted in Asia. The trial is designed to compare the effect on glycaemic control of liraglutide or glimepiride added to metformin in subjects with type 2 diabetes

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Diabetes
• Intervention / Treatment: Drug: liraglutide; Drug: placebo; Drug: liraglutide; Drug: liraglutide; Drug: metformin; Drug: placebo; Drug: glimepiride

• Study Type: Interventional
• Enrollment (Actual): 929
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shenyang, China, 110001
    • Novo Nordisk Investigational Site
  • Tianjin, China, 300052
    • Novo Nordisk Investigational Site
  • Wuhan, China, 430060
    • Novo Nordisk Investigational Site
  • Beijing
    • Beijing, Beijing, China, 100029
      • Novo Nordisk Investigational Site
    • Beijing, Beijing, China, 100730
      • Novo Nordisk Investigational Site
  • Chongqing
    • Chongqing, Chongqing, China, 400010
      • Novo Nordisk Investigational Site
  • Fujian
    • Fuzhou, Fujian, China, 350025
      • Novo Nordisk Investigational Site
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • Novo Nordisk Investigational Site
    • Harbin, Heilongjiang, China, 150086
      • Novo Nordisk Investigational Site
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Novo Nordisk Investigational Site
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Novo Nordisk Investigational Site
    • Suzhou, Jiangsu, China, 215004
      • Novo Nordisk Investigational Site
    • Wuxi, Jiangsu, China, 214023
      • Novo Nordisk Investigational Site
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Novo Nordisk Investigational Site
  • Shanghai
    • Shanghai, Shanghai, China, 200003
      • Novo Nordisk Investigational Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Novo Nordisk Investigational Site
• India
  • Cochin, India, 682 304
    • Novo Nordisk Investigational Site
  • Ghaziabad, India
    • Novo Nordisk Investigational Site
  • Kolkata, India, 700017
    • Novo Nordisk Investigational Site
  • Kolkata, India, 700026
    • Novo Nordisk Investigational Site
  • Mumbai, India, 400 0067
    • Novo Nordisk Investigational Site
  • Mumbai, India, 400016
    • Novo Nordisk Investigational Site
  • New Delhi, India, 110017
    • Novo Nordisk Investigational Site
  • Patna, India, 800020
    • Novo Nordisk Investigational Site
  • Secunderabad, India, 500 003
    • Novo Nordisk Investigational Site
  • Trivandrum, India, 695029
    • Novo Nordisk Investigational Site
  • Visakhapatnam, India, 530002
    • Novo Nordisk Investigational Site
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 500 001
      • Novo Nordisk Investigational Site
    • Hyderbad, Andhra Pradesh, India, 500 012
      • Novo Nordisk Investigational Site
  • Gujarat
    • Ahmedabad, Gujarat, India, 380 015
      • Novo Nordisk Investigational Site
  • Karnataka
    • Bangalore, Karnataka, India, 560 017
      • Novo Nordisk Investigational Site
  • Kerala
    • Cochin, Kerala, India, 695010
      • Novo Nordisk Investigational Site
  • Maharashtra
    • Mumbai, Maharashtra, India, 400010
      • Novo Nordisk Investigational Site
    • Pune, Maharashtra, India, 411 037
      • Novo Nordisk Investigational Site
  • New Delhi
    • New Dehli, New Delhi, India, 110029
      • Novo Nordisk Investigational Site
  • Orissa
    • Bhubaneswar, Orissa, India, 751019
      • Novo Nordisk Investigational Site
  • Rajasthan
    • Jaipur, Rajasthan, India, 302006
      • Novo Nordisk Investigational Site
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600 013
      • Novo Nordisk Investigational Site
    • Madurai, Tamil Nadu, India, 625 020
      • Novo Nordisk Investigational Site
  • West Bengal
    • Kolkata, West Bengal, India, 700054
      • Novo Nordisk Investigational Site
• Korea, Republic of
  • Goyang, Korea, Republic of, 410-719
    • Novo Nordisk Investigational Site
  • Incheon, Korea, Republic of, 405-220
    • Novo Nordisk Investigational Site
  • Seoul, Korea, Republic of, 03080
    • Novo Nordisk Investigational Site
  • Seoul, Korea, Republic of, 08308
    • Novo Nordisk Investigational Site
  • Seoul, Korea, Republic of, 137-701
    • Novo Nordisk Investigational Site
  • Seoul, Korea, Republic of, 130-872
    • Novo Nordisk Investigational Site
  • Seoul, Korea, Republic of, 135-710
    • Novo Nordisk Investigational Site
  • Seoul, Korea, Republic of, 150-713
    • Novo Nordisk Investigational Site
  • Sungnam, Korea, Republic of, 463-707
    • Novo Nordisk Investigational Site
  • Suwon, Korea, Republic of, 16499
    • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 2 diabetes
• Subjects diagnosed with type 2 diabetes and treated with one or more oral antidiabetic drugs (OADs) for the last 3 months
• HbA1c: 7.0-11.0% (both incl.) for subjects on OAD alone
• HbA1c: 7.0-10.0 % (both incl.) for subjects on OAD combination therapy
• BMI less than 45.0 kg/m^2

Exclusion Criteria:

• Treatment with insulin within the last 3 months prior to the trial
• Impaired liver or/and renal function
• Significant cardiovascular disease over the last 6 months
• Known retinopathy or maculopathy
• Recurrent major hypoglycaemia or hypoglycaemic unawareness

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lira 0.6 + Met; Liraglutide 0.6 mg + metformin + glimepiride placebo	Drug: liraglutide; 0.6 mg/day, s.c. (under the skin) injection; Drug: placebo; Glimepiride placebo, capsules; Drug: liraglutide; 1.2 mg/day, s.c. (under the skin) injection; Drug: liraglutide; 1.8 mg/day, s.c. (under the skin) injection; Drug: metformin; Tablets, 1.5-2.0 g/day; Drug: placebo; Liraglutide placebo, s.c. (under the skin) injection
Experimental: Lira 1.2 + Met; Liraglutide 1.2 mg + metformin + glimepiride placebo	Drug: liraglutide; 0.6 mg/day, s.c. (under the skin) injection; Drug: placebo; Glimepiride placebo, capsules; Drug: liraglutide; 1.2 mg/day, s.c. (under the skin) injection; Drug: liraglutide; 1.8 mg/day, s.c. (under the skin) injection; Drug: metformin; Tablets, 1.5-2.0 g/day; Drug: placebo; Liraglutide placebo, s.c. (under the skin) injection
Experimental: Lira 1.8 + Met; Liraglutide + metformin + glimepiride placebo	Drug: liraglutide; 0.6 mg/day, s.c. (under the skin) injection; Drug: placebo; Glimepiride placebo, capsules; Drug: liraglutide; 1.2 mg/day, s.c. (under the skin) injection; Drug: liraglutide; 1.8 mg/day, s.c. (under the skin) injection; Drug: metformin; Tablets, 1.5-2.0 g/day; Drug: placebo; Liraglutide placebo, s.c. (under the skin) injection
Experimental: Glim + Met; Glimepiride 4.0 mg + metformin + liraglutide placebo	Drug: placebo; Glimepiride placebo, capsules; Drug: metformin; Tablets, 1.5-2.0 g/day; Drug: placebo; Liraglutide placebo, s.c. (under the skin) injection; Drug: glimepiride; Capsules, 4.0 mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Glycosylated Haemoglobin A1c (HbA1c)	Percentage point change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 16 weeks (end of treatment).	week 0, week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Weight	Change in body weight from baseline (week 0) to 16 weeks (end of treatment)	week 0, week 16
Change in Self-measured Fasting Plasma Glucose	Change in self-measured fasting plasma glucose from baseline (week 0) to 16 weeks (end of treatment). Self-measurement of plasma glucose was performed using a glucose meter and subjects were instructed to record self-measured plasma glucose values into a diary.	week 0, week 16
7-point Self-measured Plasma Glucose Profiles	Summary of 7-Point Profiles of Self-Measured Plasma Glucose by Treatment, Week and Time. The 7 time points for self-measurements for all treatment groups were: Before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime, measured over 16 weeks of treatment (at week 0, 8, 12 and 16).	week 0, 8, 12 and 16
Change in Beta-cell Function	Change in beta cell function from baseline (week 0) to 16 weeks (end of treatment). Beta-cell function was derived from fasting plasma glucose (FPG) and fasting insulin concentrations using the homeostasic model assessment (HOMA) method which uses the assumption that normal-weight normal subjects aged under 35 years have a 100% beta-cell function (HOMA-B). Beta-cell function: HOMA-B (%) = 20∙fasting insulin[uU/mL] divided by (FPG mmol/L]-3.5).	week 0, week 16
Change in Fasting Lipid Profile	Change in fasting lipid profiles from baseline (week 0) to 16 weeks (end of treatment). Fasting lipid profiles is based on: Total Cholesterol (TC); Low-density Lipoprotein-cholesterol (LDL-C); Very Low-density Lipoprotein-cholesterol (VLDL-C); High-density Lipoprotein-cholesterol (HDL-C); Triglyceride (TG); Free Fatty Acid (FFA)	week 0, week 16
Change in Fasting Lipid Profile, APO-B	Change in fasting lipid profiles based on apolipoprotein B (Apo-B) from baseline (week 0) to 16 weeks (end of treatment).	week 0, week 16
Hypoglycaemic Episodes	Total number of hypoglycaemic episodes over 16 weeks of treatment occurring from baseline (week 0) to end of treatment (week 16). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose was below 3.1 mmol/L. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.	weeks 0-16

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Global Clinical Registry (GCR, 1452), MD, PhD, Novo Nordisk A/S

Publications and helpful links

General Publications

• Alves C, Batel-Marques F, Macedo AF. A meta-analysis of serious adverse events reported with exenatide and liraglutide: acute pancreatitis and cancer. Diabetes Res Clin Pract. 2012 Nov;98(2):271-84. doi: 10.1016/j.diabres.2012.09.008. Epub 2012 Sep 23.
• Jensen TM, Saha K, Steinberg WM. Is there a link between liraglutide and pancreatitis? A post hoc review of pooled and patient-level data from completed liraglutide type 2 diabetes clinical trials. Diabetes Care. 2015 Jun;38(6):1058-66. doi: 10.2337/dc13-1210. Epub 2014 Dec 12. Erratum In: Diabetes Care. 2015 Aug;38(8):1622.
• Yang W, Chen L, Ji Q, Liu X, Ma J, Tandon N, Bhattacharyya A, Kumar A, Kim KW, Yoon KH, Bech OM, Zychma M. Liraglutide provides similar glycaemic control as glimepiride (both in combination with metformin) and reduces body weight and systolic blood pressure in Asian population with type 2 diabetes from China, South Korea and India: a 16-week, randomized, double-blind, active control trial(*). Diabetes Obes Metab. 2011 Jan;13(1):81-8. doi: 10.1111/j.1463-1326.2010.01323.x.
• Ingwersen SH, Petri KC, Tandon N, Yoon KH, Chen L, Vora J, Yang W. Liraglutide pharmacokinetics and dose-exposure response in Asian subjects with Type 2 diabetes from China, India and South Korea. Diabetes Res Clin Pract. 2015 Apr;108(1):113-9. doi: 10.1016/j.diabres.2015.01.001. Epub 2015 Jan 19.
• Buse JB, Garber A, Rosenstock J, Schmidt WE, Brett JH, Videbaek N, Holst J, Nauck M. Liraglutide treatment is associated with a low frequency and magnitude of antibody formation with no apparent impact on glycemic response or increased frequency of adverse events: results from the Liraglutide Effect and Action in Diabetes (LEAD) trials. J Clin Endocrinol Metab. 2011 Jun;96(6):1695-702. doi: 10.1210/jc.2010-2822. Epub 2011 Mar 30.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): February 1, 2009

Study Registration Dates

• First Submitted: January 15, 2008
• First Submitted That Met QC Criteria: February 12, 2008
• First Posted (Estimate): February 13, 2008

Study Record Updates

• Last Update Posted (Actual): March 8, 2017
• Last Update Submitted That Met QC Criteria: January 25, 2017
• Last Verified: January 1, 2017

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; Anti-Arrhythmia Agents; Immunosuppressive Agents; Immunologic Factors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide; Metformin; Glimepiride
• Other Study ID Numbers: NN2211-1796