Effect of Metformin, Dapagliflozin, Combination of Metformin and Pioglitazone in Patients With Type 2 Diabetes

Effect of Metformin, Dapagliflozin, Fixed Combination of Metformin and Pioglitazone in Overweighted Patients With Newly Diagnosed Type 2 Diabetes

Although, a number of drugs are promising treatment strategies for insulin resistance, a critical question arises to which drug benefits patients with type 2 diabetes more from reduced insulin resistance and consequent glycemic control. In this study, we aim to evaluate the effect of metformin, dapagliflozin and the fixed-dose combination of metformin and pioglitazone (500mg metformin plus 15mg pioglitazone) on insulin sensitivity and glycemic control in overweight patients with newly diagnosed type 2 diabetes.

Study Overview

• Status: Not yet recruiting
• Conditions: Insulin Resistance; Type2diabetes
• Intervention / Treatment: Drug: Dapagliflozin; Drug: Fixed-dose combination of metformin and pioglitazone (500mg metformin plus 15mg pioglitazone); Drug: Metformin

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jianhua Ma, professor; Phone Number: 18951670116; Email: majianhua196503@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Willing to participate in this present study;
• Regular diet and exercise;
• Age 18 to 60 years;
• Screening glycated hemoglobin (HbA1c) > 9.0%;
• Body mass index (BMI) ≥ 24.0 kg/m2

Exclusion Criteria:

• Other forms of diabetes;
• Insulin allergy or intolerance of metformin, pioglitazone and dapagliflozin;
• Renal dysfunction (estimated glomerular filtration rate < 45 mL/min);
• Severe liver disease or elevated transaminases (2.5-fold the upper limit);
• History of alcohol dependence or drug abuse in the past 5 years;
• Systemic steroids therapy or other medication influencing cholesterol metabolism in the past 3 months;
• Acute infection or stress state 1 month prior to this study;
• Pregnancy or lactation;
• History of diabetic ketoacidosis (DKA) within the previous year;
• Psychiatric disease;
• Other comorbid serious condition including severe heart and pulmonary disease, heart failure of New York Heart Association class IV, and tumors.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Metformin	Drug: Dapagliflozin; After the screening period, eligible subjects took the hyperinsulinemic euglycemic clamp test and were then admitted to insulin with dapagliflozin (100mg one day) for 4 weeks. During this timeframe, all patients were instructed to change the insulin pump infusion site and provide one profile of 7-point self-monitored blood glucose every three days. The insulin doses were titrated every day by physicians to achieve the glycemic goal. Participants who failed to attain the glycemic target in three consecutive times or could not afford the side effects of hypoglycemic medications were excluded from this study. On the last day of week 4, a FreeStyle Libre Pro Sensor (FGM system) was inserted to record the glycemic data for up to 14 days. At the end of week 5, all antidiabetic agents were stopped and the hyperinsulinemic euglycemic clamp test was performed again for remaining subjects.; Drug: Fixed-dose combination of metformin and pioglitazone (500mg metformin plus 15mg pioglitazone); After the screening period, eligible subjects took the hyperinsulinemic euglycemic clamp test and were then admitted to insulin with fixed-dose combination of metformin and pioglitazone (two tablets of 500mg metformin plus 15mg pioglitazone) for 4 weeks. During this timeframe, all patients were instructed to change the insulin pump infusion site and provide one profile of 7-point self-monitored blood glucose every three days. The insulin doses were titrated every day by physicians to achieve the glycemic goal. Participants who failed to attain the glycemic target in three consecutive times or could not afford the side effects of hypoglycemic medications were excluded from this study. On the last day of week 4, a FreeStyle Libre Pro Sensor (FGM system) was inserted to record the glycemic data for up to 14 days. At the end of week 5, all antidiabetic agents were stopped and the hyperinsulinemic euglycemic clamp test was performed again for remaining subjects.
Active Comparator: Dapagliflozin	Drug: Fixed-dose combination of metformin and pioglitazone (500mg metformin plus 15mg pioglitazone); After the screening period, eligible subjects took the hyperinsulinemic euglycemic clamp test and were then admitted to insulin with fixed-dose combination of metformin and pioglitazone (two tablets of 500mg metformin plus 15mg pioglitazone) for 4 weeks. During this timeframe, all patients were instructed to change the insulin pump infusion site and provide one profile of 7-point self-monitored blood glucose every three days. The insulin doses were titrated every day by physicians to achieve the glycemic goal. Participants who failed to attain the glycemic target in three consecutive times or could not afford the side effects of hypoglycemic medications were excluded from this study. On the last day of week 4, a FreeStyle Libre Pro Sensor (FGM system) was inserted to record the glycemic data for up to 14 days. At the end of week 5, all antidiabetic agents were stopped and the hyperinsulinemic euglycemic clamp test was performed again for remaining subjects.; Drug: Metformin; After the screening period, eligible subjects took the hyperinsulinemic euglycemic clamp test and were then admitted to insulin with metformin for 4 weeks. During this timeframe, all patients were instructed to change the insulin pump infusion site and provide one profile of 7-point self-monitored blood glucose every three days. The insulin doses were titrated every day by physicians to achieve the glycemic goal. Participants who failed to attain the glycemic target in three consecutive times or could not afford the side effects of hypoglycemic medications were excluded from this study. On the last day of week 4, a FreeStyle Libre Pro Sensor (FGM system) was inserted to record the glycemic data for up to 14 days. At the end of week 5, all antidiabetic agents were stopped and the hyperinsulinemic euglycemic clamp test was performed again for remaining subjects.
Active Comparator: Fixed-dose combination of metformin and pioglitazone (500mg metformin plus 15mg pioglitazone)	Drug: Dapagliflozin; After the screening period, eligible subjects took the hyperinsulinemic euglycemic clamp test and were then admitted to insulin with dapagliflozin (100mg one day) for 4 weeks. During this timeframe, all patients were instructed to change the insulin pump infusion site and provide one profile of 7-point self-monitored blood glucose every three days. The insulin doses were titrated every day by physicians to achieve the glycemic goal. Participants who failed to attain the glycemic target in three consecutive times or could not afford the side effects of hypoglycemic medications were excluded from this study. On the last day of week 4, a FreeStyle Libre Pro Sensor (FGM system) was inserted to record the glycemic data for up to 14 days. At the end of week 5, all antidiabetic agents were stopped and the hyperinsulinemic euglycemic clamp test was performed again for remaining subjects.; Drug: Metformin; After the screening period, eligible subjects took the hyperinsulinemic euglycemic clamp test and were then admitted to insulin with metformin for 4 weeks. During this timeframe, all patients were instructed to change the insulin pump infusion site and provide one profile of 7-point self-monitored blood glucose every three days. The insulin doses were titrated every day by physicians to achieve the glycemic goal. Participants who failed to attain the glycemic target in three consecutive times or could not afford the side effects of hypoglycemic medications were excluded from this study. On the last day of week 4, a FreeStyle Libre Pro Sensor (FGM system) was inserted to record the glycemic data for up to 14 days. At the end of week 5, all antidiabetic agents were stopped and the hyperinsulinemic euglycemic clamp test was performed again for remaining subjects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin resistance	change from baseline insulin resistance at the fifth week	week 5

Collaborators and Investigators

• Sponsor: Nanjing First Hospital, Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2022
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): February 1, 2023

Study Registration Dates

• First Submitted: October 16, 2022
• First Submitted That Met QC Criteria: October 20, 2022
• First Posted (Actual): October 24, 2022

Study Record Updates

• Last Update Posted (Actual): October 24, 2022
• Last Update Submitted That Met QC Criteria: October 20, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism; Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin Resistance; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin; Metformin; Pioglitazone
• Other Study ID Numbers: KY20220314-01

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