Effect of Gemigliptin Versus Glimepiride on Cardiac Diastolic Function in Patients With Type 2 Diabetes

Comparison in Effect of Gemigliptin Versus Glimepiride on Cardiac Diastolic Function in Patients With Type 2 Diabetes Uncontrolled With Metformin

Among DPP-4 inhibitors, gemigliptin is a relatively recently developed drug, and many clinical studies have shown results that are equivalent to or superior to existing DPP-4 inhibitors such as sitagliptin. However, studies on the safety of gemigliptin in cardiovascular disease have not been conducted, and studies on its effect on cardiac function are lacking. Considering the increase in hospitalizations due to heart failure found in some DPP-4 inhibitor studies, investigation of directly effect of gemigliptin on heart function would be clinically important.

Study Overview

• Status: Recruiting
• Conditions: Ejection Fraction
• Intervention / Treatment: Drug: Gemigliptin; Drug: Glimepiride

Detailed Description

Many international guidelines including the American Diabetes Association and Korean diabetes association recommend metformin as an initial hypoglycemic agent. They also suggest early active treatment for patients with type 2 diabetes (T2D) when it is difficult to reach the target blood sugar with metformin monotherapy alone. This is a strategy to minimize the period of exposure to hyperglycemia. However, when choosing the second agent, both efficacy and safety should be considered.

The American Diabetes Association guidelines recommend to using glucagon-like peptide 1 receptor agonist (GLP-1 RAs) for patients with T2D at high atherosclerotic cardiovascular disease and sodium-glucose cotransporter-2 inhibitor for T2D patients at high risk of heart failure or chronic kidney disease. However, people at this condition are not majority in many countries.

Sulfonylurea is an oral hypoglycemic agent that was first developed in the 1950s and has been widely used for a long time. Since these sulfonylureas are complementary to metformin in their mechanism of action, sulfonylureas and metformin are one of the suitable combination therapies (Ref). In fact, in a phase 3 clinical study conducted on Koreans, compared to increasing the dose of metformin, combined administration of glimepiride and metformin proved superior in the hypoglycemic effect (Ref). However, when glimepiride and metformin were combined, hypoglycemia occurred more frequently than metformin monotherapy, and there was a side effect of weight gain (Ref). Therefore, although sulfonylurea and metformin combination therapy is an effective combination in terms of lowering blood sugar, there are doubts as to whether it is the optimal combination therapy due to side effects such as hypoglycemia and weight gain, which are disadvantages of sulfonylurea itself.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are an incretin-based therapy that have proven their hypoglycemic effect in both monotherapy and metformin combination therapy (Ref). According to the incretin-based mechanism of action, the risk of hypoglycemia is low, and the weight is neutral with DPP-4 inhibitors. In addition, it can be used without serious adverse events. On the contrary to most GLP-1 RAs, DPP-4 inhibitors are oral antidiabetic agents, which are convenient for physicians to prescribe as well as for patients to take. Of note, this class has been known to be more beneficial in Asian ethnic groups.[1] Thus, DPP-4 inhibitors have been widely used in this region.

Like sulfonylurea, when used in combination with initial metformin, it has a superior blood sugar lowering effect compared to metformin alone (Ref). However, when metformin is combined with a DPP-4 inhibitor, the risk of hypoglycemia does not increase unlike when sulfonylurea is combined. Therefore, considering the safety related to the occurrence of hypoglycemia, the DPP-4 inhibitor and metformin combination therapy may be the preferred choice over the sulfonylurea and metformin combination therapy. In several phase 3 studies and registry studies in patients with T2D who failed metformin monotherapy, the addition of a DPP-4 inhibitor to metformin was proven to be safe in hypoglycemia compared to the addition of a sulfonylurea (Ref).

Among DPP-4 inhibitors, gemigliptin is a relatively recently developed drug, and many clinical studies have shown results that are equivalent to or superior to existing DPP-4 inhibitors such as sitagliptin. However, studies on the safety of gemigliptin in cardiovascular disease have not been conducted, and studies on its effect on cardiac function are lacking. Considering the increase in hospitalizations due to heart failure found in some DPP-4 inhibitor studies, investigation of directly effect of gemigliptin on heart function would be clinically important.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Soo Lim, MD; Phone Number: 01097662706; Email: limsoo@snu.ac.kr

Study Locations

• Korea, Republic of
  • Gyeonggi
    • Seongnam, Gyeonggi, Korea, Republic of, 463-707
      • Recruiting
      • Seoul National University Bundang Hospital
      • Contact: Soo Lim, MD, PHD; Phone Number: 82-31-787-7035; Email: limsoo@snu.ac.kr
      • Principal Investigator: Soo Lim, MD, PHD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Individuals with type 2 diabetes were eligible if they were aged >20 years, had received metformin (500 mg - 2550 mg) alone for more than 6 weeks and have a glycated hemoglobin of 7%-9.5%.

Exclusion Criteria:

• if they had type 1 diabetes, were pregnant or lactating, or had New York Heart Association class III or IV heart failure. Other exclusion criteria were thyroid stimulating hormone > 10.0 IU/ml, severe infection, chronic kidney disease with eGFR < 30, AST/ALT exceeding 3 times the upper limit of the normal range, use of anti-obesity drugs within 12 weeks of the study, primary coronary intervention for acute coronary syndrome or myocardial infarction within 6 months prior to the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gemiglipitin; A DPP4 inhibitor gemigliptin treatment group	Drug: Gemigliptin; DPP-4 inhibitor; Other Names: Zemiglo
Active Comparator: Glimepiride; A sulfonylurea glimepiride treatment group	Drug: Glimepiride; Glimepiride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c	Glycated hemoglobin	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ejection fraction	Cardiac function	24 weeks
E/e'	Cardiac function	24 weeks
LV mass index	Cardiac function	24 weeks
LVEDV	Cardiac function	24 weeks
NT-proBNP	Cardiac biomarker	24 weeks
hsCRP	Cardiac biomarker	24 weeks
Adiponectin	Metabolic biomarker	24 weeks
Resistin	Metabolic biomarker	24 weeks
Troponin I	Metabolic biomarker	24 weeks
CK-MB	Metabolic biomarker	24 weeks

Collaborators and Investigators

• Sponsor: Seoul National University Bundang Hospital
• Investigators: Principal Investigator: Soo Lim, MD, SNUBH

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Anticipated): October 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: December 15, 2022
• First Submitted That Met QC Criteria: December 22, 2022
• First Posted (Estimate): December 23, 2022

Study Record Updates

• Last Update Posted (Estimate): December 23, 2022
• Last Update Submitted That Met QC Criteria: December 22, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Immunosuppressive Agents; Immunologic Factors; Glimepiride
• Other Study ID Numbers: B-1712/438-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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