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

NCT ID: NCT05663736

Last Updated: 2023-03-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-01
• Study Completion Date: 2023-12-31

Brief Summary

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.

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. 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. However, when glimepiride and metformin were combined, hypoglycemia occurred more frequently than metformin monotherapy, and there was a side effect of weight gain. 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. 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. 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. 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.

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.

Conditions

Ejection Fraction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Gemiglipitin

A DPP4 inhibitor gemigliptin treatment group

Group Type: EXPERIMENTAL

Gemigliptin

Intervention Type: DRUG

DPP-4 inhibitor

Glimepiride

A sulfonylurea glimepiride treatment group

Group Type: ACTIVE_COMPARATOR

Glimepiride

Intervention Type: DRUG

Glimepiride

Interventions

Gemigliptin

DPP-4 inhibitor

Intervention Type: DRUG

Glimepiride

Glimepiride

Intervention Type: DRUG

Other Intervention Names

Zemiglo

Eligibility Criteria

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%.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Seoul National University Bundang Hospital

OTHER

Sponsor Role: lead

Responsible Party

Soo Lim

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Soo Lim, MD

Role: PRINCIPAL_INVESTIGATOR

SNUBH

Locations

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

Soo Lim, MD

Role: CONTACT

limsoo@snu.ac.kr

01097662706

Facility Contacts

Soo Lim, MD, PHD

Role: primary

limsoo@snu.ac.kr

82-31-787-7035

Other Identifiers

B-1712/438-004

Identifier Type: -

Identifier Source: org_study_id