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Trial · Interventional

CompletedPhase 3Results postedRegistry data

A Study of Dulaglutide (LY2189265) in Participants With Type 2 Diabetes Mellitus

Short name AWARD-10

NCTNCT02597049 (opens ClinicalTrials.gov in a new tab)Other id15361Other idH9X-MC-GBGEOther id2015-002095-24Other id2015

Overview

Status
Completed
Phase
Phase 3
Enrollment
424 participants (actual)
Sponsor
Eli Lilly and Company · Industry
Design
Randomized · Double masking
Countries
9 countries

United States, Austria, Czechia, Germany, Hungary, Israel, Mexico, Puerto Rico, Spain

Start
Nov 2015
Primary completion
Feb 2017
Completion
Feb 2017
First posted
4 Nov 2015 (estimated)
Last update posted
17 Jun 2020
Conditions
Type 2 Diabetes Mellitus

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2015201620172018
  1. Ph 3

    AWARD-10

    NCT02597049

    Nov 2015 to Feb 2017

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

The main purpose of this study is to evaluate the efficacy and safety of the study drug known as dulaglutide when added to sodium-glucose co-transporter 2 (SGLT2) inhibitors in participants with type 2 diabetes mellitus.

Interventions

  • DulaglutideDrug
  • PlaceboDrug
  • SGLT2 inhibitorDrug
  • MetforminDrug

Arms3

  • Experimental

    1.5 mg Dulaglutide

    1.5 milligrams (mg) given subcutaneously (SC) once a week for 24 weeks.

  • Experimental

    0.75 mg Dulaglutide

    0.75 mg dulaglutide given SC once a week for 24 weeks.

  • Placebo comparator

    Placebo

    Placebo given SC once a week for 24 weeks.

Primary outcomes2

Outcomes the sponsor listed as primary.

  1. Change From Baseline in Hemoglobin A1c (HbA1c) at 24 Weeks (Treatment-regimen Estimand)

    Time frame · Baseline, Week 24

    Registry description

    Least Squares mean (LS) of the HbA1c change from baseline to primary endpoint at week 24 was adjusted by treatment, country, SGLT2 inhibitor dose, metformin use, treatment-by-visit interactions as fixed effects, and baseline HbA1c as a covariate and participant as a random effect, via a MMRM analysis. The treatment-regimen estimand used all data including post-rescue data and compared the benefit of treatment regimens as they were actually taken.

  2. Change From Baseline in the HbA1c at 24 Weeks (Efficacy Estimand)

    Time frame · Baseline, Week 24

    Registry description

    LS mean of the HbA1c change from baseline to primary endpoint at week 24 was adjusted by treatment, country, SGLT2 inhibitor dose, metformin use, treatment-by-visit interactions as fixed effects, and baseline HbA1c as a covariate and participant as a random effect, via a MMRM analysis. The efficacy estimand excluded post-rescue data and compared the benefit of randomized treatments when taken as directed without rescue medication.

Secondary outcomes(9)
  1. Percentage of Participants With HbA1c <7%

    Time frame · 24 Weeks

    Registry description

    Number of participants with an HbA1c value of \<7% at Week 24 is measured using longitudinal logistic regression with repeated measurements. The model will include independent variables of treatment, country, SGLT2 inhibitor dose, metformin use, visit, treatment-by-visit interaction, and baseline HbA1c as a covariate.

  2. Change From Baseline in Body Weight at 24 Weeks

    Time frame · Baseline, Week 24

    Registry description

    LS mean of the body weight change from baseline to primary endpoint at week 24 was adjusted by treatment, country, SGLT2 inhibitor dose, metformin use, baseline HbA1c strata, treatment-by-visit interactions as fixed effects, and baseline body weight as a covariate and participant as a random effect, via a MMRM analysis

  3. Change From Baseline in Fasting Serum Glucose (Central Laboratory) at 24 Weeks

    Time frame · Baseline, Week 24

    Registry description

    LS mean of change from baseline was calculated using last observation carried forward (LOCF) by treatment group, adjusted for treatment, country, SGLT2 inhibitor dose, metformin use, baseline HbA1c strata, and baseline fasting serum glucose using analysis of covariance (ANCOVA).

  4. Change From Baseline in 6-Point Self-Monitored Plasma Glucose (SMPG) Profile at 24 Weeks

    Time frame · Baseline, Week 24

    Registry description

    The self-monitored plasma glucose (SMPG) data were collected at the following 6 time points: pre-morning meal; 2 hours post-morning meal; pre-midday meal; 2 hours post-midday meal; pre-evening meal; 2 hours post-evening meal. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, metformin use, SGLT2 inhibitor use, country, visit, baseline HbA1c strata, and treatment-by-visit interaction as fixed effects and baseline as a covariate.

  5. Change From Baseline in Fasting Glucagon at 24 Weeks

    Time frame · Baseline, Week 24

    Registry description

    Change from baseline in fasting glucagon was analyzed using an ANCOVA model with last observation carried forward (LOCF) included in treatment, country, SGLT2i dose, metformin use, and baseline HbA1c strata as fixed effects and baseline fasting glucagon as a covariate (with and without post rescue data).

  6. Rate of Hypoglycemic Events Adjusted Per 30 Days

    Time frame · Baseline through 24 Weeks

    Registry description

    A hypoglycemic event is defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a PG level of ≤70 mg/dL (≤3.9 mmol/L).

  7. Number of Participants Requiring Rescue Therapy Due to Severe Persistent Hyperglycemia

    Time frame · Baseline through 24 Weeks

    Registry description

    Rescue therapy was defined as any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation.

  8. Number of Participants With Adjudicated Acute Pancreatitis Events

    Time frame · Baseline through 24 Weeks

    Registry description

    The number of participants with events of pancreatitis confirmed by adjudication were summarized cumulatively at 24 weeks. Pancreatitis events were adjudicated by a committee of physicians external to the Sponsor. A summary of serious and other non-serious events regardless of causality is located in the Reported Adverse Events module.

  9. Number of Participants With Adjudicated Cardiovascular (CV) Events

    Time frame · Baseline through 24 Weeks

    Registry description

    Death and selected nonfatal CV adverse events (AEs) were adjudicated by an independent committee of physicians with cardiology expertise external to the Sponsor. Nonfatal CV events that were to be adjudicated were myocardial infarction (MI); hospitalization for unstable angina; hospitalization for heart failure; coronary interventions such as coronary artery bypass graft (CABG) or ( percutaneous coronary intervention (PCI); and cerebrovascular events, including cerebrovascular accident (stroke) and transient ischemic attack (TIA).

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeLeast squares mean· Baseline, Week 24

Change From Baseline in Hemoglobin A1c (HbA1c) at 24 Weeks (Treatment-regimen Estimand)

GroupValue (percentage of HbA1c)Spread
1.5 mg Dulaglutide-1.340.064
0.75 mg Dulaglutide-1.210.064
Placebo-0.540.064
Primary outcomeLeast squares mean· Baseline, Week 24

Change From Baseline in the HbA1c at 24 Weeks (Efficacy Estimand)

GroupValue (percentage of HbA1c)Spread
1.5 mg Dulaglutide-1.330.063
0.75 mg Dulaglutide-1.190.063
Placebo-0.510.065
Secondary and other outcome results(6)
Secondary outcomeNumber· 24 Weeks

Percentage of Participants With HbA1c <7%

GroupValue (percentage of participants)
1.5 mg Dulaglutide71.21
0.75 mg Dulaglutide60.45
Placebo31.58
Secondary outcomeLeast squares mean· Baseline, Week 24

Change From Baseline in Body Weight at 24 Weeks

GroupValue (kilograms (kg))Spread
1.5 mg Dulaglutide-3.10.30
0.75 mg Dulaglutide-2.60.30
Placebo-2.10.30
Secondary outcomeLeast squares mean· Baseline, Week 24

Change From Baseline in Fasting Serum Glucose (Central Laboratory) at 24 Weeks

GroupValue (milligram/deciliter (mg/dL))Spread
1.5 mg Dulaglutide-31.62.17
0.75 mg Dulaglutide-26.52.18
Placebo-6.92.21
Secondary outcomeLeast squares mean· Baseline, Week 24

Change From Baseline in 6-Point Self-Monitored Plasma Glucose (SMPG) Profile at 24 Weeks

GroupValue (mg/dL)Spread
1.5 mg Dulaglutide-27.82.13
0.75 mg Dulaglutide-23.22.17
Placebo-8.12.14
Secondary outcomeLeast squares mean· Baseline, Week 24

Change From Baseline in Fasting Glucagon at 24 Weeks

GroupValue (picomole per liter (pmol/L))Spread
1.5 mg Dulaglutide-2.10.39
0.75 mg Dulaglutide-1.50.39
Placebo-0.90.40
Secondary outcomeMean· Baseline through 24 Weeks

Rate of Hypoglycemic Events Adjusted Per 30 Days

GroupValue (Number of events/participant/30 days)Spread
1.5 mg Dulaglutide0.0260.1827
0.75 mg Dulaglutide0.0220.1375
Placebo0.0170.1320

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
1.5 mg DulaglutideDulaglutide 1.5 milligrams (mg) given SC QW for 24 weeks.2 / 1425 / 14243 / 142
0.75 mg DulaglutideDulaglutide 0.75 mg given subcutaneously (SC) once a week (QW) for 24 weeks.0 / 1413 / 14134 / 141
PlaceboPlacebo given SC QW for 24 weeks.0 / 1405 / 14029 / 140

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies2

Studies that cite this trial.

More studies

2 studies on this page

Indexing hint: Meta-analysis (pooled) · 2023

Weight-dependent and weight-independent effects of dulaglutide on blood pressure in patients with type 2 diabetes.

Ferdinand et al. 2023Cardiovascular diabetologycited by 12

PMID 36894938PMC9999488DOI 10.1186/s12933-023-01775-xPUB-36894938

CC BY
Download PDF

Indexing hint: Randomized controlled trial · 2018

Corrected

Dulaglutide as add-on therapy to SGLT2 inhibitors in patients with inadequately controlled type 2 diabetes (AWARD-10): a 24-week, randomised, double-blind, placebo-controlled trial.

Ludvik et al. 2018The lancet. Diabetes & endocrinologycited by 205

PMID 29483060DOI 10.1016/s2213-8587(18)30023-8PUB-29483060

Rights unknown

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * Have type 2 diabetes mellitus (based on the World Health Organization's \[WHO\] diagnostic criteria) * Have been treated with an SGLT2 inhibitor, with or without metformin, for at least 3 months prior to study entry (minimum required doses for that period for allowed SGLT2 inhibitors: empagliflozin 10 mg, dapagliflozin 5 or 10 mg \[per country-specific label\], canagliflozin 100 mg); minimum required dose for metformin, if used, is ≥1500 mg/day and must be reached (or highest tolerated dose which is acceptable with documented gastrointestinal \[GI\] intolerability) * Daily doses of all allowed oral antihyperglycemia agent (OAMs) must have been stable for at least 12 weeks (±3 days) prior to randomization (study enrollment); daily doses of SGLT2 inhibitor and metformin, if used, will be considered stable during this period if: * all prescribed daily doses were in the range between the minimum required dose and maximum-approved dose per country-specific label; and * \>90% of prescribed daily doses were equal to the dose at randomization * Have HbA1c ≥7.0% and ≤9.5% at study entry and approximately 1 week prior to randomization * Have body mass index (BMI) ≤45 kilograms per meter squared (kg/m\^2) and agree to not initiate a diet and/or exercise program during the study with the intent of reducing body weight other than the lifestyle and dietary measures for diabetes treatment Exclusion Criteria: * Have type 1 diabetes mellitus * Have been treated with any other OAMs (other than SGLT2 inhibitors and metformin), glucagon-like peptide-1 receptor agonist (GLP-1 RA), pramlintide or insulin 3 months prior to study entry, or between study entry and randomization; or initiate metformin between study entry and randomization; short-term use of insulin for acute care (≤14 days) during the 3-month period prior to entry is not exclusionary * Have any condition that is a contraindication for use of the GLP-1 RA class or the SGLT2 inhibitor class (per country-specific labels) at study entry or develop such condition between study entry and randomization * Have acute or chronic hepatitis, signs and symptoms of any other liver disease other than nonalcoholic fatty liver disease (NAFLD), or alanine transaminase (ALT) level \>2.5 times the upper limit of the reference range, as determined by the central laboratory at study entry; participants with NAFLD are eligible for participation in this trial * Had chronic or acute pancreatitis any time prior to study entry * Estimated glomerular filtration rate (eGFR) \<45 milliliters(mL)/minute/1.73m\^2, calculated by the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation, as determined by the central laboratory at study entry and confirmed at lead in * Have any self or family history of type 2A or type 2B multiple endocrine neoplasia (MEN 2A or 2B) in the absence of known C-cell hyperplasia (this exclusion includes participants with a family history of MEN 2A or 2B, whose family history for the syndrome is rearranged during transfect \[RET\]-negative; the only exception for this exclusion will be for participants whose family members with MEN 2A or 2B have a known RET mutation and the potential participant for the study is negative for the RET mutation) * Have any self or family history of medullary C-cell hyperplasia, focal hyperplasia, carcinoma (including sporadic, familial, or part of MEN 2A or 2B syndrome) * Have a serum calcitonin ≥20 picograms/mL as determined by the central laboratory at study entry

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