Linagliptin Response to OGTT in Prediabetes and Type 2 Diabetes Mellitus

Association of Fasting GLP-1 Level With the Effect of Linagliptin After an Oral Glucose Tolerance Test in Prediabetes and Type 2 Diabetes Mellitus

There are studies that suggest glycemic response to incretin-based therapies differs between Asians and Caucasians, whereby Asians have better response compared to Caucasians. Hence, the therapeutic response could also be augmented by difference in incretin system among various ethnicities. This study is carried out to study the effect of dipeptidyl-peptidase IV (DPPIV) inhibitors in prediabetes and T2DM patients who have different levels of GLP-1 and to determine the effect on glycemic profiles, insulin resistance/sensitivity, beta-cell functon.

Study Overview

• Status: Completed
• Conditions: PreDiabetes; Type 2 Diabetes
• Intervention / Treatment: Drug: Dipeptidyl-Peptidase IV Inhibitors

Detailed Description

A 12-week, open-label, single treatment study using linagliptin is conducted in 28 prediabetes and 22 T2DM subjects who are divided into low and high fasting GLP-1 groups. Prediabetes are recruited from OGTT screening. Type 2 diabetes patients are recruited from specialised diabetes clinic and routine follow-up. A 75-g oral glucose tolerance test (OGTT) is performed at week 0 and 12. Venous blood samples were drawn at times 0 (before initiation of OGTT), 30, 60, 90, 120 min from the indwelling catheter for measurement of glucose and insulin.All prediabetes and T2DM subjects receive Linagliptin 5mg once daily for a duration of 12 weeks.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• Malaysia
  • Johor
    • Johor Bahru, Johor, Malaysia, 81100
      • Hospital Sultan Ismail

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Prediabetes diagnosed from OGTT and T2DM subjects
• HbA1c > 6.5% and <10%
• Subjects not receiving any glucose-lowering medication or just receiving metformin and/or sulphonylureas and/or alpha-glucosidase inhibitors on stable dose for at least 3 months.
• Subjects who are willing to participate and sign the informed consent form

Exclusion Criteria:

• Subjects with ketoacidosis or lactic acidosis, overt diabetes, another disease causing secondary glucose intolerance, congestive heart failure (New York Heart Association Class III or IV), myocardial infarction, stroke or ischemic attacks in past 6 months, uncontrolled severe hypertension, active liver conditions such as cirrhosis or hepatitis [elevation in liver enzymes to higher activities than double the respective normal value], moderate to severe renal insufficiency, pregnancy, breast-feeding
• Patients receiving insulin, GLP-1 receptor agonists, dipeptidyl peptidase IV inhibitors or glucose-lowering medications other than metformin /sulphonylureas /alpha-glucosidase inhibitors as treatment.
• Subjects with uncontrolled blood glucose HbA1c>10%
• Subjects who plan to move out of state / country

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Prediabetes Low GLP-1; prediabetes patients were divided into high GLP-1 and low GLP-1 groups based on the median of fasting GLP-1 level. linagliptin 5mg once daily was administered.	Drug: Dipeptidyl-Peptidase IV Inhibitors; All subjects were given linagliptin 5mg once daily for 12 weeks. Comparison of their OGTT response at week 0 and week 12; Other Names: linagliptin
Active Comparator: Prediabetes High GLP-1; prediabetes patients were divided into high GLP-1 and low GLP-1 groups based on the median of fasting GLP-1 level. linagliptin 5mg once daily was administered.	Drug: Dipeptidyl-Peptidase IV Inhibitors; All subjects were given linagliptin 5mg once daily for 12 weeks. Comparison of their OGTT response at week 0 and week 12; Other Names: linagliptin
Active Comparator: Diabetes Low GLP-1; type 2 diabetes mellitus patients were divided into high GLP-1 and low GLP-1 groups based on the median of fasting GLP-1 level. linagliptin 5mg once daily was administered.	Drug: Dipeptidyl-Peptidase IV Inhibitors; All subjects were given linagliptin 5mg once daily for 12 weeks. Comparison of their OGTT response at week 0 and week 12; Other Names: linagliptin
Active Comparator: Diabetes High GLP-1; type 2 diabetes mellitus patients were divided into high GLP-1 and low GLP-1 groups based on the median of fasting GLP-1 level. linagliptin 5mg once daily was administered.	Drug: Dipeptidyl-Peptidase IV Inhibitors; All subjects were given linagliptin 5mg once daily for 12 weeks. Comparison of their OGTT response at week 0 and week 12; Other Names: linagliptin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change from baseline in glucose after 12-week treatment	OGTT is performed at week 0 (baseline) and 12 (complete treatment). plasma glucose levels are taken at time 0,30,60,90,120 minutes during OGTT.	baseline to 12 weeks
change from baseline in HbA1c after 12-week treatment	plasma level of fasting HbA1c is taken at week 0 and 12 of study before OGTT	baseline to 12 weeks
change from baseline in insulin sensitivity/resistance index after 12-week treatment	OGTT is performed at week 0 (baseline) and 12. Plasma levels of glucose and insulin are taken at time 0,30,60,90,120 min during the OGTT. HOMA-IR, HOMA-IS are used to measure insulin resistance and insulin sensitivity at week 0 and week 12	baseline to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change from baseline in beta-cell function after 12-week treatment	OGTT is performed at week 0 (baseline) and 12 (treatment complete). HOMS-beta, insulinogenic index, oral disposition index are used to measure beta-cell funciton at week 0 and 12	baseline to 12 weeks

Collaborators and Investigators

• Sponsor: National University of Malaysia
• Investigators: Principal Investigator: SHIAU CHONG, National University of Malaysia

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Actual): March 1, 2021
• Study Completion (Actual): March 1, 2021

Study Registration Dates

• First Submitted: February 25, 2022
• First Submitted That Met QC Criteria: March 13, 2022
• First Posted (Actual): March 22, 2022

Study Record Updates

• Last Update Posted (Actual): March 22, 2022
• Last Update Submitted That Met QC Criteria: March 13, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: type 2 diabetes; prediabetes; oral glucose tolerance test; glucagon-like peptide 1; Dipeptidyl peptidase inhibitor
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperglycemia; Diabetes Mellitus; Diabetes Mellitus, Type 2; Prediabetic State; Glucose Intolerance; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Linagliptin; Dipeptidyl-Peptidase IV Inhibitors
• Other Study ID Numbers: Linagliptin study

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