Head-to-head Comparison of Empagliflozin and Dapagliflozin

Head-to-head Comparison of Quadruple Combination Therapy With Empagliflozin and Dapagliflozin in Patients With Poorly Controlled Type 2 Diabetes (T2D) Despite Three Existing Oral Antidiabetic Drugs (OAD)

This open-labeled, prospective, observational, 3-year, clinical study was conducted to compare the effectiveness and safety between empagliflozin (25 mg once daily) and dapagliflozin (10 mg once daily) in patients with inadequately controlled type 2 diabetes despite preexisting triple OAD combination.

Study Overview

• Status: Completed
• Conditions: Type2 Diabetes
• Intervention / Treatment: Drug: Empagliflozin; Drug: Dapagliflozin

Detailed Description

All participants included in this study were initially requested to initiate therapy with insulin, but they insisted on another form of OAD. When participants declined insulin injection and requested another OAD, they were not randomly assigned to each groups. It is fairly common among participants with T2D to decline insulin therapy, despite being aware of its importance and the benefits in controlling blood glucose. Their lack of willingness to use insulin is explained by their avoidance of painful injections, the potential for body weight gain and their fear of hypoglycemia. The investigators conducted a regimen consisting of four OADs, including empagliflozin or dapagliflozin, to confirm which regimen would be effective and safe.

• Study Type: Observational
• Enrollment (Actual): 600

Contacts and Locations

Study Locations

• Korea, Republic of
  • Chungcheongbuk-do
    • Cheonju, Chungcheongbuk-do, Korea, Republic of, 28644
      • Chungbuk National University Hospital

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

• Sampling Method: Non-Probability Sample

Study Population

The targeted population consists of adult patients with type 2 diabetes mellitus treated in outpatient setting by specialists

Description

Inclusion Criteria:

• Inadequately controlled under triple OADs (metformin, glimepiride, dipeptidyl peptidase inhibitor) as evidenced by HbA1c 7.5-12%

Exclusion Criteria:

• Type 1 diabetes
• Gestational diabetes
• Diabetes due to secondary causes
• Receiving anticancer treatment
• Receiving glucocorticoids or immune-suppressants
• have been treated with sodium-glucose co-transporter 2 inhibitors for more than 7 consecutive days within 3 months before entering this study

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Triple OADs failure; Empagliflozin or dapagliflozin as an add-on drug for inadequately controlled T2D patients who are already receiving a regimen of three distinct OADs, including metformin, glimepiride and dipeptidyl peptidase 4 (DPP4) inhibitors.	Drug: Empagliflozin; Empagliflozin 25 mg once daily add on the background OADs for 3 years; Other Names: Metformin; Glimepiride; DPP4 inhibitor; Drug: Dapagliflozin; Dapagliflozin 25 mg once daily add on the background OADs for 3 years; Other Names: Metformin; Glimepiride; DPP4 inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in HbA1c from baseline to week 156 (3-year)	Changes in HbA1c from baseline to week 156 (3-year)	Baseline, week 156 (3-year)
Changes in fasting plasma glucose from baseline to week 156 (3-year)	Changes in fasting plasma glucose from baseline to week 156 (3-year)	Baseline, week 156 (3-year)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in HbA1c from baseline to week 104 (2-year)	Changes in HbA1c from baseline to week 104 (2-year)	Baseline, week 104 (2-year)
Changes in HbA1c from baseline to week 52 (1-year)	Changes in HbA1c from baseline to week 52 (1-year)	Baseline, week 52 (1-year)
Changes in HbA1c from baseline to week 24	Changes in HbA1c from baseline to week 24	Baseline, Week 24
Changes in fasting plasma glucose from baseline to week 12	Changes in fasting plasma glucose from baseline to week 12	Baseline, Week 12
Changes in fasting plasma glucose from baseline to week 24	Changes in fasting plasma glucose from baseline to week 24	Baseline, Week 24
Changes in fasting plasma glucose from baseline to week 56 (1-year)	Changes in fasting plasma glucose from baseline to week 56 (1-year)	Baseline, Week 56 (1-year)
Changes in weight between baseline and week 156 (3-year)	Changes in weight between baseline and week 156 (3-year)	Baseline, Week 156 (3-year)
Changes in weight between baseline and week 104 (2-year)	Changes in weight between baseline and week 104 (2-year)	Baseline, Week 104 (2-year)
Changes in weight between baseline and week 52	Changes in weight between baseline and week 52	Baseline, Week 52
Changes in weight between baseline and week 24	Changes in weight between baseline and week 24	Baseline, Week 24
Changes in weight between baseline and week 12	Changes in weight between baseline and week 12	Baseline, Week 12
Changes in systolic blood pressure between baseline and week 156 (3-year)	Changes in systolic blood pressure between baseline and week 156 (3-year)	Baseline, Week 156 (3-year)
Changes in systolic blood pressure between baseline and week 104 (2-year)	Changes in systolic blood pressure between baseline and week 104 (2-year)	Baseline, Week 104 (2-year)
Changes in systolic blood pressure between baseline and week 52	Changes in systolic blood pressure between baseline and week 52	Baseline, Week 52
Changes in systolic blood pressure between baseline and week 24	Changes in systolic blood pressure between baseline and week 24	Baseline, Week 24
Changes in systolic blood pressure between baseline and week 12	Changes in systolic blood pressure between baseline and week 12	Baseline, Week 12
Changes in diastolic blood pressure between baseline and week 156 (3-year)	Changes in diastolic blood pressure between baseline and week 156 (3-year)	Baseline, Week 156 (3-year)
Changes in diastolic blood pressure between baseline and week 104 (2-year)	Changes in diastolic blood pressure between baseline and week 104 (2-year)	Baseline, Week 104 (2-year)
Changes in diastolic blood pressure between baseline and week 52	Changes in diastolic blood pressure between baseline and week 52	Baseline, Week 52
Changes in diastolic blood pressure between baseline and week 24	Changes in diastolic blood pressure between baseline and week 24	Baseline, Week 24
Changes in diastolic blood pressure between baseline and week 12	Changes in diastolic blood pressure between baseline and week 12	Baseline, Week 12
Changes in total cholesterol between baseline and week 156 (3-year)	Changes in total cholesterol between baseline and week 156 (3-year)	Baseline, Week 156 (3-year)
Changes in triglyceride between baseline and week 156 (3-year)	Changes in triglyceride between baseline and week 156 (3-year)	Baseline, Week 156 (3-year)
Changes in LDL-cholesterol between baseline and week 156 (3-year)	Changes in LDL-cholesterol between baseline and week 156 (3-year)	Baseline, Week 156 (3-year)
Changes in HDL-cholesterol between baseline and week 156 (3-year)	Changes in HDL-cholesterol between baseline and week 156 (3-year)	Baseline, Week 156 (3-year)
Percentage of patients with hypoglycemic episodes between baseline and week 156 (3-year)	All episodes consistent with hypoglycemic episodes with or without a confirmatory blood glucose reading were collected	Baseline, Week 156 (3-year)
Percentage of patients with at least 1 episode of genitourinary tract infections between baseline and week 156 (3-year)	Percentage of patients with at least 1 episode of genitourinary tract infections	Baseline, Week 156 (3-year)

Collaborators and Investigators

• Sponsor: Chungbuk National University Hospital
• Investigators: Study Chair: Jae Hyun Ahn, Chungbuk National University Hospital

Publications and helpful links

General Publications

• Ku EJ, Lee DH, Jeon HJ, Oh TK. Long-term effectiveness and safety of quadruple combination therapy with empagliflozin versus dapagliflozin in patients with type 2 diabetes: 3-year prospective observational study. Diabetes Res Clin Pract. 2021 Dec;182:109123. doi: 10.1016/j.diabres.2021.109123. Epub 2021 Nov 3.
• Ku EJ, Lee DH, Jeon HJ, Oh TK. Empagliflozin versus dapagliflozin in patients with type 2 diabetes inadequately controlled with metformin, glimepiride and dipeptidyl peptide 4 inhibitors: A 52-week prospective observational study. Diabetes Res Clin Pract. 2019 May;151:65-73. doi: 10.1016/j.diabres.2019.04.008. Epub 2019 Apr 4.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: November 19, 2018
• First Submitted That Met QC Criteria: November 19, 2018
• First Posted (Actual): November 21, 2018

Study Record Updates

• Last Update Posted (Actual): July 20, 2022
• Last Update Submitted That Met QC Criteria: July 19, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Dapagliflozin; Empagliflozin; Sodium-glucose cotransporter 2 inhibitors; Quadruple combination antidiabetic drugs
• 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; Protease Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin; Metformin; Empagliflozin; Glimepiride; Dipeptidyl-Peptidase IV Inhibitors
• Other Study ID Numbers: SGLT2 inhibitor 2018

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No