Efficacy and Safety of Empagliflozin (BI 10773) Versus Placebo and Sitagliptin Over 24 Weeks in Patients With Type 2 Diabetes

A Phase III Randomised, Double-blind, Placebo-controlled Parallel Group Efficacy and Safety Study of BI 10773 and Sitagliptin Administered Orally Over 24 Weeks, in Drug naïve Patients With Type 2 Diabetes Mellitus and Insufficient Glycaemic Control Despite Diet and Exercise

The aim of this study is to investigate the efficacy, safety and tolerability of BI 10773 compared to placebo and sitagliptin given for 24 weeks as monotherapy in patients with T2DM with insufficient glycaemic control. For the open-label part of the study the objective is to estimate the efficacy and safety of BI 10773 when given for 24 weeks in patients with T2DM with very poor glycaemic control.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: BI 10773; Drug: Placebo identical to BI10773 high dose; Drug: Placebo identical to Sitagliptin 100mg; Drug: Placebo identical to BI10773 low dose; Drug: BI10773; Drug: Sitagliptin; Drug: BI 10773 open label

• Study Type: Interventional
• Enrollment (Actual): 986
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium
    • 1245.20.32008 Boehringer Ingelheim Investigational Site
  • Bruxelles, Belgium
    • 1245.20.32011 Boehringer Ingelheim Investigational Site
  • Bruxelles, Belgium
    • 1245.20.32023 Boehringer Ingelheim Investigational Site
  • De Pinte, Belgium
    • 1245.20.32003 Boehringer Ingelheim Investigational Site
  • Deurne, Belgium
    • 1245.20.32015 Boehringer Ingelheim Investigational Site
  • Deurne, Belgium
    • 1245.20.32016 Boehringer Ingelheim Investigational Site
  • Gozée, Belgium
    • 1245.20.32025 Boehringer Ingelheim Investigational Site
  • Landen, Belgium
    • 1245.20.32022 Boehringer Ingelheim Investigational Site
  • Leopoldsburg, Belgium
    • 1245.20.32019 Boehringer Ingelheim Investigational Site
  • Linkebeek, Belgium
    • 1245.20.32024 Boehringer Ingelheim Investigational Site
  • Mouscron, Belgium
    • 1245.20.32021 Boehringer Ingelheim Investigational Site
  • Retie, Belgium
    • 1245.20.32027 Boehringer Ingelheim Investigational Site
  • Sint-Gillis-Waas, Belgium
    • 1245.20.32020 Boehringer Ingelheim Investigational Site
  • Tielt, Belgium
    • 1245.20.32018 Boehringer Ingelheim Investigational Site
  • Tremelo, Belgium
    • 1245.20.32026 Boehringer Ingelheim Investigational Site
• Canada
  • British Columbia
    • Chilliwack, British Columbia, Canada
      • 1245.20.20011 Boehringer Ingelheim Investigational Site
    • Victoria, British Columbia, Canada
      • 1245.20.20018 Boehringer Ingelheim Investigational Site
  • Manitoba
    • Winnipeg, Manitoba, Canada
      • 1245.20.20015 Boehringer Ingelheim Investigational Site
  • New Brunswick
    • Moncton, New Brunswick, Canada
      • 1245.20.20012 Boehringer Ingelheim Investigational Site
  • Newfoundland and Labrador
    • Mount Pearl, Newfoundland and Labrador, Canada
      • 1245.20.20016 Boehringer Ingelheim Investigational Site
    • St. John's, Newfoundland and Labrador, Canada
      • 1245.20.20008 Boehringer Ingelheim Investigational Site
  • Ontario
    • Barrie, Ontario, Canada
      • 1245.20.20001 Boehringer Ingelheim Investigational Site
    • Hamilton, Ontario, Canada
      • 1245.20.20019 Boehringer Ingelheim Investigational Site
    • London, Ontario, Canada
      • 1245.20.20010 Boehringer Ingelheim Investigational Site
    • London, Ontario, Canada
      • 1245.20.20017 Boehringer Ingelheim Investigational Site
    • Markham, Ontario, Canada
      • 1245.20.20003 Boehringer Ingelheim Investigational Site
    • Newmarket, Ontario, Canada
      • 1245.20.20009 Boehringer Ingelheim Investigational Site
    • Ottawa, Ontario, Canada
      • 1245.20.20013 Boehringer Ingelheim Investigational Site
    • Strathroy, Ontario, Canada
      • 1245.20.20005 Boehringer Ingelheim Investigational Site
    • Toronto, Ontario, Canada
      • 1245.20.20002 Boehringer Ingelheim Investigational Site
    • Toronto, Ontario, Canada
      • 1245.20.20006 Boehringer Ingelheim Investigational Site
  • Prince Edward Island
    • Charlottetown, Prince Edward Island, Canada
      • 1245.20.20014 Boehringer Ingelheim Investigational Site
    • Montague, Prince Edward Island, Canada
      • 1245.20.20007 Boehringer Ingelheim Investigational Site
  • Quebec
    • Trois Rivieres, Quebec, Canada
      • 1245.20.20021 Boehringer Ingelheim Investigational Site
• China
  • Beijing, China
    • 1245.20.86007 Boehringer Ingelheim Investigational Site
  • Beijing, China
    • 1245.20.86008 Boehringer Ingelheim Investigational Site
  • Guangzhou, China
    • 1245.20.86001 Boehringer Ingelheim Investigational Site
  • Guangzhou, China
    • 1245.20.86002 Boehringer Ingelheim Investigational Site
  • Guangzhou, China
    • 1245.20.86003 Boehringer Ingelheim Investigational Site
  • Guiyang, China
    • 1245.20.86012 Boehringer Ingelheim Investigational Site
  • Hangzhou, China
    • 1245.20.86020 Boehringer Ingelheim Investigational Site
  • Jinan, China
    • 1245.20.86049 Boehringer Ingelheim Investigational Site
  • Jingzhou, China
    • 1245.20.86018 Boehringer Ingelheim Investigational Site
  • Nanchang, China
    • 1245.20.86019 Boehringer Ingelheim Investigational Site
  • Nanjing, China
    • 1245.20.86010 Boehringer Ingelheim Investigational Site
  • Nanjing, China
    • 1245.20.86043 Boehringer Ingelheim Investigational Site
  • QingDao, China
    • 1245.20.86016 Boehringer Ingelheim Investigational Site
  • Shanghai, China
    • 1245.20.86004 Boehringer Ingelheim Investigational Site
  • Shanghai, China
    • 1245.20.86005 Boehringer Ingelheim Investigational Site
  • Shanghai, China
    • 1245.20.86006 Boehringer Ingelheim Investigational Site
  • Shenyang, China
    • 1245.20.86057 Boehringer Ingelheim Investigational Site
  • Shiyan, China
    • 1245.20.86017 Boehringer Ingelheim Investigational Site
  • Suzhou, China
    • 1245.20.86013 Boehringer Ingelheim Investigational Site
  • Taiyuan, China
    • 1245.20.86015 Boehringer Ingelheim Investigational Site
  • Wuhan, China
    • 1245.20.86009 Boehringer Ingelheim Investigational Site
  • Xi'An, China
    • 1245.20.86011 Boehringer Ingelheim Investigational Site
  • Xiamen, China
    • 1245.20.86014 Boehringer Ingelheim Investigational Site
• Germany
  • Dresden, Germany
    • 1245.20.49013 Boehringer Ingelheim Investigational Site
  • Düsseldorf, Germany
    • 1245.20.49016 Boehringer Ingelheim Investigational Site
  • Frankfurt, Germany
    • 1245.20.49015 Boehringer Ingelheim Investigational Site
  • Haag, Germany
    • 1245.20.49019 Boehringer Ingelheim Investigational Site
  • Hohenmölsen, Germany
    • 1245.20.49020 Boehringer Ingelheim Investigational Site
  • Köthen, Germany
    • 1245.20.49014 Boehringer Ingelheim Investigational Site
  • Neuwied, Germany
    • 1245.20.49002 Boehringer Ingelheim Investigational Site
  • Nürnberg, Germany
    • 1245.20.49008 Boehringer Ingelheim Investigational Site
  • Schauenburg, Germany
    • 1245.20.49022 Boehringer Ingelheim Investigational Site
  • St. Ingbert/Oberwürzbach, Germany
    • 1245.20.49017 Boehringer Ingelheim Investigational Site
  • Unterschneidheim, Germany
    • 1245.20.49003 Boehringer Ingelheim Investigational Site
• India
  • Bangalore, India
    • 1245.20.91005 Boehringer Ingelheim Investigational Site
  • Bangalore, India
    • 1245.20.91006 Boehringer Ingelheim Investigational Site
  • Bangalore, India
    • 1245.20.91008 Boehringer Ingelheim Investigational Site
  • Belgaum, India
    • 1245.20.91003 Boehringer Ingelheim Investigational Site
  • Chennai, India
    • 1245.20.91004 Boehringer Ingelheim Investigational Site
  • Chennai, India
    • 1245.20.91009 Boehringer Ingelheim Investigational Site
  • Mumbai, India
    • 1245.20.91002 Boehringer Ingelheim Investigational Site
  • Mumbai, Maharastra, India
    • 1245.20.91007 Boehringer Ingelheim Investigational Site
  • Nagpur, India
    • 1245.20.91010 Boehringer Ingelheim Investigational Site
  • Tamil Nadu, India
    • 1245.20.91001 Boehringer Ingelheim Investigational Site
• Ireland
  • Co. Cork, Ireland
    • 1245.20.35302 Boehringer Ingelheim Investigational Site
  • Co. Galway, Ireland
    • 1245.20.35305 Boehringer Ingelheim Investigational Site
  • Co. Wexford, Ireland
    • 1245.20.35303 Boehringer Ingelheim Investigational Site
  • Offaly, Ireland
    • 1245.20.35304 Boehringer Ingelheim Investigational Site
  • Wexford, Ireland
    • 1245.20.35306 Boehringer Ingelheim Investigational Site
• Japan
  • Chiyoda-ku, Tokyo, Japan
    • 1245.20.81007 Boehringer Ingelheim Investigational Site
  • Chuo-ku, Tokyo, Japan
    • 1245.20.81001 Boehringer Ingelheim Investigational Site
  • Chuo-ku, Tokyo, Japan
    • 1245.20.81002 Boehringer Ingelheim Investigational Site
  • Ebetsu, Hokkaido, Japan
    • 1245.20.81005 Boehringer Ingelheim Investigational Site
  • Kamakura, Kanagawa, Japan
    • 1245.20.81004 Boehringer Ingelheim Investigational Site
  • Minato-ku, Tokyo, Japan
    • 1245.20.81003 Boehringer Ingelheim Investigational Site
  • Shinjuku-ku, Tokyo, Japan
    • 1245.20.81006 Boehringer Ingelheim Investigational Site
  • Shinjuku-ku, Tokyo, Japan
    • 1245.20.81008 Boehringer Ingelheim Investigational Site
  • Suita, Osaka, Japan
    • 1245.20.81009 Boehringer Ingelheim Investigational Site
  • Ube, Yamaguchi, Japan
    • 1245.20.81010 Boehringer Ingelheim Investigational Site
  • Urasoe, Okinawa, Japan
    • 1245.20.81012 Boehringer Ingelheim Investigational Site
  • Urasoe, Okinawa, Japan
    • 1245.20.81013 Boehringer Ingelheim Investigational Site
• Switzerland
  • Lugano, Switzerland
    • 1245.20.41004 Boehringer Ingelheim Investigational Site
  • Rorschach, Switzerland
    • 1245.20.41003 Boehringer Ingelheim Investigational Site
• United States
  • Arizona
    • Mesa, Arizona, United States
      • 1245.20.10124 Boehringer Ingelheim Investigational Site
    • Phoenix, Arizona, United States
      • 1245.20.10108 Boehringer Ingelheim Investigational Site
  • Arkansas
    • Hot Springs, Arkansas, United States
      • 1245.20.10150 Boehringer Ingelheim Investigational Site
  • California
    • Chino, California, United States
      • 1245.20.10154 Boehringer Ingelheim Investigational Site
    • Santa Ana, California, United States
      • 1245.20.10009 Boehringer Ingelheim Investigational Site
    • West Hills, California, United States
      • 1245.20.10131 Boehringer Ingelheim Investigational Site
  • Colorado
    • Northglenn, Colorado, United States
      • 1245.20.10038 Boehringer Ingelheim Investigational Site
  • Florida
    • Clearwater, Florida, United States
      • 1245.20.10137 Boehringer Ingelheim Investigational Site
    • Miami, Florida, United States
      • 1245.20.10006 Boehringer Ingelheim Investigational Site
    • Plantation, Florida, United States
      • 1245.20.10085 Boehringer Ingelheim Investigational Site
    • Tampa, Florida, United States
      • 1245.20.10078 Boehringer Ingelheim Investigational Site
  • Georgia
    • Decatur, Georgia, United States
      • 1245.20.10080 Boehringer Ingelheim Investigational Site
  • Indiana
    • Avon, Indiana, United States
      • 1245.20.10128 Boehringer Ingelheim Investigational Site
    • Fishers, Indiana, United States
      • 1245.20.10060 Boehringer Ingelheim Investigational Site
    • Indianapolis, Indiana, United States
      • 1245.20.10065 Boehringer Ingelheim Investigational Site
  • Kansas
    • Arkansas City, Kansas, United States
      • 1245.20.10117 Boehringer Ingelheim Investigational Site
    • Wichita, Kansas, United States
      • 1245.20.10039 Boehringer Ingelheim Investigational Site
  • Kentucky
    • Louisville, Kentucky, United States
      • 1245.20.10146 Boehringer Ingelheim Investigational Site
  • Massachusetts
    • Watertown, Massachusetts, United States
      • 1245.20.10144 Boehringer Ingelheim Investigational Site
  • New Jersey
    • Brick, New Jersey, United States
      • 1245.20.10115 Boehringer Ingelheim Investigational Site
  • Ohio
    • Carlisle, Ohio, United States
      • 1245.20.10129 Boehringer Ingelheim Investigational Site
    • Cincinnati, Ohio, United States
      • 1245.20.10045 Boehringer Ingelheim Investigational Site
    • Cincinnati, Ohio, United States
      • 1245.20.10119 Boehringer Ingelheim Investigational Site
    • Gallipolis, Ohio, United States
      • 1245.20.10130 Boehringer Ingelheim Investigational Site
  • Texas
    • Houston, Texas, United States
      • 1245.20.10089 Boehringer Ingelheim Investigational Site
    • Hurst, Texas, United States
      • 1245.20.10151 Boehringer Ingelheim Investigational Site
    • San Antonio, Texas, United States
      • 1245.20.10155 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

1. Diagnosis of type 2 diabetes mellitus prior to informed consent;
2. Male and female patients on diet and exercise regimen who are drug-naïve;
3. HbA1c >= 7.0% and <= 10.0% at Visit 1 (screening) for randomised treatment; HbA1c > 10.0% at visit 1 (screening) for the open-label BI 10773 arm;
4. Age >= 20 (Japan); Age >= 18 (countries other than Japan);
5. BMI <= 45 kg/m2 at Visit 1 (screening);
6. Signed and dated written informed consent by date of Visit 1

Exclusion criteria:

1. Uncontrolled hyperglycaemia;
2. Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or TIA within 3 months prior to informed consent;
3. Indication of liver disease, either ALT, AST, or alkaline phosphatase above 3 x ULN;
4. Impaired renal function (eGFR<50 ml/min);
5. Bariatric surgery within the past two years or other GI surgeries;
6. Medical history of cancer;
7. Contraindications to sitagliptin;
8. Blood dyscrasias or any disorders causing haemolysis or unstable red blood cell;
9. Treatment with any anti-diabetes drug within 12 weeks prior to randomisation;
10. Treatment with anti-obesity drugs or any other treatment leading to unstable body weight;
11. Current treatment with systemic steroids or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except T2DM;
12. Pre-menopausal women who are nursing or pregnant or are of child-bearing potential and not practicing an acceptable method of birth control;
13. Alcohol or drug abuse;
14. Intake of an investigational drug in another trial within 30 days prior to intake of study medication in this trial;
15. Any other clinical condition that would jeopardize patients safety while participating in this clinical trial

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BI 10773 low dose; Patients receive BI 10773 low dose tablets once daily	Drug: BI 10773; BI 10773 low dose tablet once daily; Drug: Placebo identical to BI10773 high dose; placebo tablets once daily; Drug: Placebo identical to Sitagliptin 100mg; placebo tablets once daily
Experimental: BI 10773 high dose; Patients receive BI 10773 high dose tablets once daily	Drug: Placebo identical to Sitagliptin 100mg; placebo tablets once daily; Drug: Placebo identical to BI10773 low dose; placebo tablets once daily; Drug: BI10773; BI 10773 high dose tablets once daily
Placebo Comparator: Placebo; Patients receive tablets identical to those containing BI 10773 low dose and high dose and to Sitagliptin	Drug: Placebo identical to BI10773 high dose; placebo tablets once daily; Drug: Placebo identical to Sitagliptin 100mg; placebo tablets once daily; Drug: Placebo identical to BI10773 low dose; placebo tablets once daily
Active Comparator: Sitagliptin 100 mg; Patients receive Sitagliptin 100 mg tablets once daily	Drug: Placebo identical to BI10773 high dose; placebo tablets once daily; Drug: Placebo identical to BI10773 low dose; placebo tablets once daily; Drug: Sitagliptin; Sitagliptin tablets 100 mg once daily
Experimental: BI 10773 high dose open label; Patients receive BI 10773 high dose tablets open label once daily	Drug: BI 10773 open label; Patients receive BI 10773 high dose tablets open label once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Glycosylated Haemoglobin (HbA1c) After 24 Weeks	The term "baseline" refers to the last observation before the start of randomised trial treatment (or of open-label treatment for the open-label arm). In this endpoint, the "measured values" show unadjusted values, whereas the statistical analyses show adjusted values. Statistics for open-label group are descriptive.	Baseline and day 169

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 24 in Body Weight	The term "baseline" refers to the last observation before the start of randomised trial treatment (or of open-label treatment for the open-label arm). In this endpoint, the "measured values" show unadjusted values, whereas the statistical analyses show adjusted values. Statistics for open-label group are descriptive.	Baseline and day 169
Change From Baseline to Week 24 in Systolic and Diastolic Blood Pressure (SBP and DBP)	The term "baseline" refers to the last observation before the start of randomised trial treatment (or of open-label treatment for the open-label arm). In this endpoint, the "measured values" show unadjusted values, whereas the statistical analyses show adjusted values. Statistics for open-label group are descriptive. For blood pressure, data following changes in antihypertensive therapy is censored, in the same way that data following initiation of rescue medication is censored.	Baseline and week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed Hypoglycaemic Adverse Events	Confirmed hypoglycaemic events refer to all hypoglycaemic events, that had a glucose value <= 70 ml/dL or where assistance was required. Symptomatic hypoglycaemic events were to be reported as adverse events. Patients can be counted in more than one category.	From first drug intake until 7 days after last medication intake, up to 219 days

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Collaborators: Eli Lilly and Company

Publications and helpful links

General Publications

• Tuttle KR, Levin A, Nangaku M, Kadowaki T, Agarwal R, Hauske SJ, Elsasser A, Ritter I, Steubl D, Wanner C, Wheeler DC. Safety of Empagliflozin in Patients With Type 2 Diabetes and Chronic Kidney Disease: Pooled Analysis of Placebo-Controlled Clinical Trials. Diabetes Care. 2022 Jun 2;45(6):1445-1452. doi: 10.2337/dc21-2034.
• Cherney D, Lund SS, Perkins BA, Groop PH, Cooper ME, Kaspers S, Pfarr E, Woerle HJ, von Eynatten M. The effect of sodium glucose cotransporter 2 inhibition with empagliflozin on microalbuminuria and macroalbuminuria in patients with type 2 diabetes. Diabetologia. 2016 Sep;59(9):1860-70. doi: 10.1007/s00125-016-4008-2. Epub 2016 Jun 17.
• Roden M, Weng J, Eilbracht J, Delafont B, Kim G, Woerle HJ, Broedl UC; EMPA-REG MONO trial investigators. Empagliflozin monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2013 Nov;1(3):208-19. doi: 10.1016/S2213-8587(13)70084-6. Epub 2013 Sep 9.

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: July 29, 2010
• First Submitted That Met QC Criteria: August 6, 2010
• First Posted (Estimate): August 9, 2010

Study Record Updates

• Last Update Posted (Estimate): June 16, 2014
• Last Update Submitted That Met QC Criteria: May 16, 2014
• Last Verified: May 1, 2014

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; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Empagliflozin; Sitagliptin Phosphate
• Other Study ID Numbers: 1245.20; 2009-016243-20 (EudraCT Number: EudraCT)