The Efficacy of Sodium-glucose Co-transporter 2 Inhibitor or Dipeptidyl Peptidase-4 Inhibitor in Type 2 Diabetes Patients With Premix Insulin

The Efficacy and Safety of Sodium-glucose Co-transporter 2 Inhibitor or Dipeptidyl Peptidase 4 Inhibitor Added to Premix Insulin Injection Twice Daily in Uncontrolled Type 2 Diabetes Patients

The population of type 2 diabetes increased enormously worldwide. As disease progression, uncontrolled type 2 diabetes patients need multiple daily insulin injections, but the risk of body weight gain and hypoglycemia will increase. In recent years, the newly oral anti-hypoglycemic agents developed, such as dipeptidyl peptidase-4 inhibitors (DPP4i) and sodium-glucose co-transporter 2 inhibitors (SGLT2i). The former indirectly stimulate insulin secretion and suppress glucagon through increase incretin. The later inhibit re-absorption of blood glucose in proximal renal tubule to improve hyperglycemia. According to the guideline published in 2017 by American diabetes Associations, if patients received premix insulin injections twice daily and their glycemic control can't meet the target, increase the frequency of injection such as basal bolus would be considered. However, it is difficult for some patients and it may cause more hypoglycemia and gain of body weight. Because previous report revealed dipeptidyl peptidase-4 inhibitors or sodium-glucose co-transporter 2 inhibitors added to insulin resulted in better glycemic control, but there was no direct comparison, so we design this study to observe the efficacy of these two drugs in uncontrolled diabetes patient received twice daily insulin injections.

Study Overview

• Status: Unknown
• Conditions: Type2 Diabetes
• Intervention / Treatment: Drug: SGLT2 inhibitor (Empagliflozin 25 MG); Drug: DPP4 inhibitor (Linagliptin 5 MG)

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yi-Hong Zeng, MD; Phone Number: +886-975835827; Email: starrydouchain@yahoo.com.tw

Study Locations

• Taiwan
  • Taipei, Taiwan, 10449
    • Recruiting
    • Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital
    • Contact: Yi-Hong Zeng, MD; Phone Number: 2174 +886-2-25433535; Email: starrydouchain@yahoo.com.tw
    • Sub-Investigator: Sung-Chen Liu, MD
    • Sub-Investigator: Chun-Chuan Lee, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 2 diabetes patient received premix insulin twice daily and HbA1c>7%
• >20 years old

Exclusion Criteria:

• Type 1 diabetes and gestational diabetes
• Diabetic ketoacidosis in previous 6 months
• Urinary tract infection in previous 6 months
• Pancreatitis in previous 6 months
• estimated GFR<45 mL/min/1.73m2
• Patient whom already received DPP4 inhibitor or SGLT2 inhibitor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SGLT2 inhibitor (Empagliflozin 25 MG); We add SGLT2 inhibitor (Empagliflozin 25 MG, oral, once daily) to type 2 diabetes patient poorly controlled with premix insulin therapy for 6 months.	Drug: SGLT2 inhibitor (Empagliflozin 25 MG); We randomized add SGLT2 inhibitor (Empagliflozin 25 MG) or DPP4 inhibitor (Linagliptin 5 MG) to type 2 diabetes patient poorly controlled with premix insulin therapy.; Other Names: Jardiance
ACTIVE_COMPARATOR: DPP4 inhibitor (Linagliptin 5 MG); We add DPP4 inhibitor (Linagliptin 5 MG, oral, once daily) to type 2 diabetes patient poorly controlled with premix insulin therapy.for 6 months.	Drug: DPP4 inhibitor (Linagliptin 5 MG); We randomized add SGLT2 inhibitor (Empagliflozin 25 MG) or DPP4 inhibitor (Linagliptin 5 MG) to type 2 diabetes patient poorly controlled with premix insulin therapy.; Other Names: Trajenta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycated hemoglobin (HbA1c)	change in glycated hemoglobin (HbA1c) in percentage from baseline to week 24	measurement at baseline, 12 week and 24 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting blood glucose	change in fasting blood glucose in mg/dl from baseline to week 24	measurement at baseline, 12 week and 24 week
Postprandial blood glucose	change in postprandial blood glucose in mg/dl from baseline to week 24	measurement at baseline, 12 week and 24 week
Body weight	change in body weight in kilogram from baseline to week 24	measurement at baseline, 12 week and 24 week
Hypoglycemia event	documented hypoglycemia (glucose monitor <70mg/dl with hypoglycemia associated symptoms) from baseline to week 24	recorded at 12 week and 24 week

Collaborators and Investigators

• Sponsor: Mackay Memorial Hospital

Publications and helpful links

General Publications

• Zeng YH, Liu SC, Lee CC, Sun FJ, Liu JJ. Effect of empagliflozin versus linagliptin on body composition in Asian patients with type 2 diabetes treated with premixed insulin. Sci Rep. 2022 Oct 12;12(1):17065. doi: 10.1038/s41598-022-21486-9.
• Liu SC, Lee CC, Chuang SM, Sun FJ, Zeng YH. Comparison of efficacy and safety of empagliflozin vs linagliptin added to premixed insulin in patients with uncontrolled type 2 diabetes: A randomized, open-label study. Diabetes Metab. 2021 May;47(3):101184. doi: 10.1016/j.diabet.2020.08.001. Epub 2020 Aug 19.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 21, 2017
• Primary Completion (ANTICIPATED): September 21, 2018
• Study Completion (ANTICIPATED): November 21, 2018

Study Registration Dates

• First Submitted: October 26, 2017
• First Submitted That Met QC Criteria: March 7, 2018
• First Posted (ACTUAL): March 8, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 8, 2018
• Last Update Submitted That Met QC Criteria: March 7, 2018
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: DPP4 inhibitor; SGLT2 inhibitor
• 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; Empagliflozin; Linagliptin; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors
• Other Study ID Numbers: 17MMHIS083

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

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