A Comparison of Two Treatment Strategies in Older Participants With Type 2 Diabetes Mellitus (T2DM) (IMPERIUM)

An Individualized treatMent aPproach for oldER patIents: A Randomized, Controlled stUdy in Type 2 Diabetes Mellitus (IMPERIUM)

The main purpose of this study is to compare the benefits and risks associated with the use of 2 treatment strategies to lower blood sugar in participants aged 65 and older with T2DM. One strategy is based on the use of oral and injectable medications that only reduce blood sugar (glucose) when it is high. The other strategy is based on non-glucose dependent agents. The trial will last up to 72 weeks for each participant.

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Metformin; Drug: Insulin Glargine; Drug: Sitagliptin; Drug: Glimepiride; Drug: Pioglitazone; Drug: Acarbose; Drug: Linagliptin; Drug: Liraglutide; Drug: Exenatide once weekly (QW); Drug: Exenatide twice daily (BID)

• Study Type: Interventional
• Enrollment (Actual): 192
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Saint Stefan Ob Stainz, Austria, A-8511
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Salzburg, Austria, 5026
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Vienna, Austria, A-1060
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Wien, Austria, A 1210
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Germany
  • Berlin, Germany, 10409
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Dortmund, Germany, 44137
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Hamburg, Germany, 22607
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Mainz, Germany, 55116
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Münster, Germany, 48145
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Neuwied, Germany, 56564
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Stuttgart, Germany, 70378
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Puerto Rico
  • Manati, Puerto Rico, 00674
    • Manati Medical Center
  • San Juan, Puerto Rico, 00917-3104
    • American Telemedicine Center
• United Kingdom
  • Manchester, United Kingdom, M41 5SL
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Manchester
    • Salford, Manchester, United Kingdom, M6 8HD
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Scotland
    • Dundee, Scotland, United Kingdom, DD1 9SY
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S5 7AU
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Suffolk
    • Ipswich, Suffolk, United Kingdom, IP4 5PD
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• United States
  • Florida
    • Miami, Florida, United States, 33175
      • New Horizon Research Center
    • Miami, Florida, United States, 33135
      • Suncoast Research Group, LLC
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research
    • Orlando, Florida, United States, 32804
      • Florida Hospital
  • Georgia
    • Athens, Georgia, United States, 30606
      • Athens Primary Care
    • Suwanee, Georgia, United States, 30024
      • Herman Clinical Research, LLC
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Rocky Mountain Diabetes and Osteoporosis Center
  • Iowa
    • Des Moines, Iowa, United States, 50314
      • Iderc, P.L.C.
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Mercy Health Research
  • New Hampshire
    • Nashua, New Hampshire, United States, 03063
      • Southern New Hampshire Diabetes and Endocrinology
  • Pennsylvania
    • Beaver, Pennsylvania, United States, 15009
      • Heritage Valley Medical Group, Inc.
    • Levittown, Pennsylvania, United States, 19056
      • Family Medical Associates
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Health Specialists
  • Texas
    • Dallas, Texas, United States, 75230
      • Dallas Diabetes Endocrine Center
  • Washington
    • Spokane, Washington, United States, 99202
      • Rockwood Clinic Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have T2DM based on a history and clinical impression that is consistent with the World Health Organization (WHO) Classification of Diabetes
• Have a Clinical Frailty Scale (CFS) score of 4 or above or Total Illness Burden Index (TIBI) score of 5 or above as assessed at screening
• Have an A1c >7.3% and <10.9% at study entry and are not achieving desired glycemic control as evidenced by A1c measurement at least 0.4% higher than individualized treatment target set at screening.

• Have been treated for at least 3 months prior to the study entry with any of the following treatment options:

  • Diet/exercise only (only if they have known contraindications to metformin treatment)
  • Any dose of sulfonylurea

  • Effective or maximally-tolerated doses of metformin, dipeptidyl-peptidase-4 (DPP-4) inhibitor, thiazolidinedione, or acarbose used in monotherapy or in dual combination. The following doses are considered to be effective:

    • at least 1500 mg of metformin per day
    • At least 30 mg of pioglitazone per day
    • At least 4 mg of rosiglitazone per day
    • At least 75 mg of acarbose per day
    • Any marketed dose of DPP-4 inhibitor

Exclusion Criteria:

• Are currently enrolled in a clinical trial involving an investigational product or nonapproved use of a drug or device (other than the investigational product used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
• Have participated, within the last 60 days in a clinical trial involving an investigational product other than the investigational product used in this study. If the previous investigational product has a long half-life, 3 months or 5 half-lives (whichever is longer) should have passed
• Have previously completed or withdrawn from this study. This exclusion criterion does not apply to participants who are rescreened prior to randomization
• At study entry, have contraindications to sulfonylurea, insulin, or GLP-1 RA
• Have a history of pancreatitis, a personal or family history of medullary thyroid carcinoma, or have Multiple Endocrine Neoplasia syndrome type 2
• Have taken any injectable glucose-lowering agent, miglitol, meglitinide, Sodium/Glucose cotransporter-2 inhibitor, or other antihyperglycemia treatment that is not listed in the fourth inclusion criterion for more than 10 days within 3 months prior to the study entry
• In the opinion of investigator should have an individualized A1c target set at 8% or higher
• Have a body mass index (BMI) greater than 45 kg/m^2
• Have had more than 1 episode of severe hypoglycemia within 24 weeks prior to the study
• Have cardiac disease with functional status that is Class III or IV according to the New York Heart Association Cardiac Disease Classification
• Have an estimated glomerular filtration rate (eGFR) <30 milliliter/minute/1.73 m^2 (mL/min/1.73 m^2) or advanced renal disease including history of renal transplantation or currently receiving renal dialysis
• Have obvious clinical signs or symptoms or laboratory evidence of liver disease (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 2.5 times the upper limit of the reference range)
• Receive current therapy for a malignancy, other than basal-cell or squamous-cell skin cancer
• Received systemic glucocorticoids within the 3 months prior to entry for more than 14 consecutive days
• Have any other condition that precludes the participant from following and completing the study

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
Experimental: Strategy A (Glucose-Dependent); Participants may receive oral and injectable (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) therapies that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label. Treatment may last up to 72 weeks.	Drug: Metformin; Administered orally; Drug: Sitagliptin; Administered orally; Drug: Pioglitazone; Administered orally; Drug: Acarbose; Administered orally; Drug: Linagliptin; Administered orally; Drug: Liraglutide; Administered subcutaneously (SC); Drug: Exenatide once weekly (QW); Administered SC; Drug: Exenatide twice daily (BID); Administered SC
Active Comparator: Strategy B (Reference); Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Insulin glargine is titrated according treatment algorithm. Treatment may last up to 72 weeks.	Drug: Metformin; Administered orally; Drug: Insulin Glargine; Administered SC; Drug: Sitagliptin; Administered orally; Drug: Glimepiride; Administered orally; Drug: Pioglitazone; Administered orally; Drug: Acarbose; Administered orally; Drug: Linagliptin; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving and Maintaining Individualized Glycated Hemoglobin A1c (HbA1c) Targets Without Clinically Significant Hypoglycemia	Failed to reach and maintain HbA1c target, without clinically significant hypoglycemia, is defined as having 2 consecutive HbA1c > upper limit of HbA1c target over 12 weeks starting from Week 24 for participants with HbA1c data beyond Week 24, or Week 24 HbA1c > upper limit of HbA1c target for participants without HbA1c data beyond Week 24. Clinically significant hypoglycemia is defined as any severe hypoglycemia or repeated hypoglycemia interrupting participants activities or sleep and associated with blood glucose ≤3.9 millimole per liter (mmol/L), or repeated asymptomatic hypoglycemia associated with blood glucose <3.0 mmol/L. Success is defined as lacking of failure.	Baseline to last participant visit (up to 72 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Requiring Alternative Treatment Due to Glycemic Failure of First Line Injectable Therapy		Baseline to last participant visit (up to 72 weeks)
Number of Participants With Total Hypoglycemia and Other Categories of Hypoglycemia		Baseline to last participant visit (up to 72 weeks)
Change From Baseline of Urinary Albumin to Creatinine Ratio	The Urinary Albumin to Creatinine Ratio is used in addition to Estimated Glomerular Filtration Rate (eGFR) to measure the incidence and progression of diabetic kidney disease.	Baseline, Week 72
Change From Baseline in Body Mass Index (BMI)		Baseline, Week 72
Change From Baseline of Estimated Glomerular Filtration Rate (eGFR)	The eGFR is used in addition to the Urinary Albumin to Creatinine Ratio to measure the incidence and progression of diabetic kidney disease.	Baseline, Week 72

Other Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Adult Low Blood Sugar Survey (ALBSS) Score	Baseline, Week 72
Change From Baseline in European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Score	Baseline, Week 72
Change From Baseline in Mini-mental State Examination (MMSE) Score	Baseline, Week 72

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Heller SR, Pratley RE, Sinclair A, Festa A, Kiljanski J, Brusko CS, Duan R, Heine RJ. Glycaemic outcomes of an Individualized treatMent aPproach for oldER vulnerable patIents: A randomized, controlled stUdy in type 2 diabetes Mellitus (IMPERIUM). Diabetes Obes Metab. 2018 Jan;20(1):148-156. doi: 10.1111/dom.13051. Epub 2017 Aug 8.

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: February 24, 2014
• First Submitted That Met QC Criteria: February 24, 2014
• First Posted (Estimate): February 26, 2014

Study Record Updates

• Last Update Posted (Actual): October 9, 2019
• Last Update Submitted That Met QC Criteria: September 25, 2019
• Last Verified: September 1, 2019

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; Anti-Arrhythmia Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Anti-Obesity Agents; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Glycoside Hydrolase Inhibitors; Liraglutide; Metformin; Insulin Glargine; Pioglitazone; Linagliptin; Sitagliptin Phosphate; Glimepiride; Exenatide; Acarbose
• Other Study ID Numbers: 14842; F3Z-MC-IOQL (Other Identifier: Eli Lilly and Company); 2013-001473-24 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR