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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
424
Administered SC
Administered SC
Administered orally as standard of care for type 2 diabetes
Change From Baseline in Hemoglobin A1c (HbA1c) at 24 Weeks (Treatment-regimen Estimand)
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.
Time frame: Baseline, Week 24
Change From Baseline in the HbA1c at 24 Weeks (Efficacy Estimand)
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.
Time frame: Baseline, Week 24
Percentage of Participants With HbA1c <7%
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.
Time frame: 24 Weeks
Change From Baseline in Body Weight at 24 Weeks
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
Time frame: Baseline, Week 24
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Administered orally as standard of care for type 2 diabetes
Medical Group of Encino
Encino, California, United States
National Research Institute
Huntington Park, California, United States
National Research Institute
Los Angeles, California, United States
New Horizon Research Center
Miami, Florida, United States
Metabolic Research Institute Inc.
West Palm Beach, Florida, United States
Cotton O'Neil Diabetes and Endocrinology Center
Topeka, Kansas, United States
JCMG Clinical Research
Jefferson City, Missouri, United States
Grand Street Medical PC
Brooklyn, New York, United States
Diabetes & Endocrinology Consultants PC
Morehead City, North Carolina, United States
PMG Research of Wilmington, LLC
Wilmington, North Carolina, United States
...and 31 more locations
Change From Baseline in Fasting Serum Glucose (Central Laboratory) at 24 Weeks
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).
Time frame: Baseline, Week 24
Change From Baseline in 6-Point Self-Monitored Plasma Glucose (SMPG) Profile at 24 Weeks
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.
Time frame: Baseline, Week 24
Change From Baseline in Fasting Glucagon at 24 Weeks
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).
Time frame: Baseline, Week 24
Rate of Hypoglycemic Events Adjusted Per 30 Days
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).
Time frame: Baseline through 24 Weeks
Number of Participants Requiring Rescue Therapy Due to Severe Persistent Hyperglycemia
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.
Time frame: Baseline through 24 Weeks
Number of Participants With Adjudicated Acute Pancreatitis Events
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.
Time frame: Baseline through 24 Weeks
Number of Participants With Adjudicated Cardiovascular (CV) Events
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).
Time frame: Baseline through 24 Weeks