Triple Combination Therapy in Type 2 Diabetic Patients Who Had Inadequate Glycemic Control With Combination Therapy

Therapeutic Efficacy and Safety of Sitagliptin, Dapagliflozin and Lobeglitazone in Patients With Type 2 Diabetes Mellitus Inadequately Controlled on Glimepiride and Metformin.

To assess the efficacy of treatment with sitagliptin or dapagliflozin or lobeglitazone in type 2 diabetes mellitus patients, who had inadequate glycemic control even though use of two drug combination therapy with glimepiride and metformin.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Metformin; Drug: Sitagliptin; Drug: Glimepirde; Drug: Dapagliflozin; Drug: Lobeglitazone

Detailed Description

Dual combination therapy with metformin and sulphonylurea is the most commonly used combination regimen to treat patients with type 2 diabetes. But, treatment with the dual combination therapy is often unsuccessful at achieving glycaemic control in patients with type 2 diabetes.

Recently, various oral hypoglycemic agents were developed including dipeptidyl peptidase (DPP)-IV inhibitor, sodium-glucose cotransporter 2 (SGLT2) inhibitor and new peroxisome proliferator-activated receptors (PPARs) agonists.

But, there have been few studies about the glucose lowering effect of these drugs in Type 2 diabetes patients on the dual combination therapy with a sulfonylurea agent and metformin.

Hence, the researchers plan to investigate the efficacy and safety of these drugs in combination with a sulfonylurea agent and metformin in type 2 diabetic patients.

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyeonggi
    • Seongnam, Gyeonggi, Korea, Republic of, 463-707
      • Soo Lim

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 20 ≤ Age < 80 years
• HbA1c ≥ 7 %
• combination therapy with glimepiride and metformin over 2 months.
• dosage of glimepiride : 1-8mg/day
• dosage of metformin : 500-2550mg/day

Exclusion Criteria:

• Type 1 diabetes, gestational diabetes, or secondary forms of diabetes
• Contraindication to sitagliptin or dapagliflozin or lobeglitazone
• Pregnant or breast feeding women
• Medication which affect glycemic control (ex. steroid)
• Disease which affect efficacy and safety of drugs
• Any major illness (Liver disease, Renal failure, Heart disease, Cancer, etc)
• Not appropriate for oral antidiabetic agent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Glimepirde, Metformin, Sitagliptin; Dipeptidyl peptidase-4 (DPP4) inhibitor Sitagliptin	Drug: Metformin; Drug: Sitagliptin; 100mg qd per oral during 24months compared with other treatment groups; Other Names: Januvia; Drug: Glimepirde; Other Names: Amaryl
Active Comparator: Glimepirde, Metformin, Dapagliflozin; Sodium-glucose cotransporter 2 (SGLT2) inhibitors Dapagliflozin	Drug: Metformin; Drug: Glimepirde; Other Names: Amaryl; Drug: Dapagliflozin; 10mg qd per oral during 24months compared with other treatment groups; Other Names: Forxiga
Active Comparator: Glimepirde, Metformin, Lobeglitazone; Peroxisome proliferator-activated receptor gamma agonist Lobeglitazone	Drug: Metformin; Drug: Glimepirde; Other Names: Amaryl; Drug: Lobeglitazone; 0.5mg qd per oral during 24months compared with other treatment groups; Other Names: Duvie

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycemic target goal achievement rate	HbA1c< 7.0% without hypoglycemia	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beta-cell function	Beta-cell function	6 and 24 months
insulin resistance	insulin resistance	6 and 24 months
Fasting blood sugar (FBS) and Post Prandial 2 hour blood glucose (PP2)	Fasting blood sugar (FBS) and Post Prandial 2 hour blood glucose (PP2)	3,6,9,12,16,20 and 24months
Lipid profile	Lipid profile	3,6,9,12,16,20 and 24months
Body fat	Body fat	6,12 and 24 months
urine microalbumin to creatinine ratio	urine microalbumin to creatinine ratio	6,12 and 24 months
Change of HbA1c	Change of HbA1c	3,6,9,12,16,20 and 24months
Glycemic target goal achievement rate	HbA1c< 7.0% without hypoglycemia	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
hypoglycemia	hypoglycemia	3,6,9,12,16,20 and 24months
body weight change	body weight change	6 and 24 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): November 30, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: January 11, 2015
• First Submitted That Met QC Criteria: January 13, 2015
• First Posted (Estimate): January 14, 2015

Study Record Updates

• Last Update Posted (Actual): January 4, 2022
• Last Update Submitted That Met QC Criteria: January 2, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: sitagliptin; dapagliflozin; triple combination therapy; lobeglitazone
• 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; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Dapagliflozin; Metformin; Sitagliptin Phosphate
• Other Study ID Numbers: Triple_3