Metabolic Responses of Dapagliflozin vs Sitagliptin in T2DM Patients Inadequately Controlled With Insulin Therapy

NCT03959501 | Completed Phase 4

• 1 other identifier: UW-17-166
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The use of sodium glucose co-transporter 2 inhibitors (SGLT2i) has been associated with increased serum ketone levels. However, most previous studies included subjects who were either insulin or even drug naïve with relatively short duration of diabetes. It is well known that insulin deficiency increases the risk of developing ketoacidosis with SGLT2 inhibitors. Moreover, since the glucose-lowering effect of SGLT2 inhibitors is at its maximum at 3 to 6 months after use, the extent of increase in serum ketone levels and its clinical relevance with chronic use of SGLT2 inhibitors, especially among insulin-treated patients that often have longer duration of diabetes and potentially more insulin deficient than those who are insulin naive, have not been clearly defined. Therefore, the investigators perform this randomised study to evaluate the effect of SGLT2 inhibitors on serum ketone levels among Chinese patients with T2DM inadequately controlled with insulin therapy.

Conditions

Type 2 Diabetes; Ketonemia

Keywords

Type 2 diabetes; Sodium glucose co-transporter 2 inhibitors; Ketones

Outcome Measures

Primary Outcomes (1)

• Change in serum ketone levels after treatment

  Change in serum ketone levels before and after treatment with either dapagliflozin or sitagliptin for 24 weeks

  24 weeks

Secondary Outcomes (8)

• Change in fasting glucose

  24 weeks

• Change in glycated haemoglobin

  24 weeks

• Change in body weight

  24 weeks

• Change in blood pressure

  24 weeks

• Change in fasting lipid

  24 weeks

Study Arms (2)

Dapagliflozin

EXPERIMENTAL

Dapagliflozin 10mg daily PO for 24 weeks

Drug: Dapagliflozin 10 mg

Sitagliptin

ACTIVE COMPARATOR

Sitagliptin 100mg daily PO for 24 weeks

Drug: Sitagliptin 100mg

Interventions

Dapagliflozin 10 mg DRUG

Dapagliflozin 10mg daily for 24 weeks

Also known as: Forxiga

Dapagliflozin

Sitagliptin 100mg DRUG

Sitagliptin 100mg daily for 24 weeks

Also known as: Januvia

Sitagliptin

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chinese
• Aged 21 to 75 both inclusive
• Type 2 diabetes on single or two doses of insulin therapy with or without metformin, which include intermediate acting human insulin, premixed human insulin or insulin analogues
• On stable insulin doses, as defined by less than 10% changes in total daily insulin dose within 3 months prior to randomization
• Suboptimal glycaemic control with baseline HbA1c ≥8.0% and ≤10.5%, taken within 2 months prior to randomization
• Body mass index between 21 and 40 kg/m2

You may not qualify if:

• Type 1 diabetes mellitus
• History of ketoacidosis
• Concurrent use of sulphonylurea or glucagon like peptide-1 receptor (GLP1) agonists
• Prior use of SGLT2 inhibitors, DPP4-inhibitors or GLP1 agonists within 3 months of randomization
• History of intolerance to SGLT2 inhibitors or DPP4-inhibitors
• Concurrent use of loop diuretics
• eGFR \<45 ml/min/1.73m2 within 3 months prior to randomization
• History of acute or chronic pancreatitis
• History of benign or malignant pancreatic tumours
• History of bladder cancer
• Alcohol or drug abuse
• Pregnant or nursing women
• Women at childbearing age not using and refused to start chemical or mechanical contraception after randomization
• Severe liver disease with elevated plasma alanine aminotransferase (ALT) of more than five times the upper limit of normal, taken within 3 months prior to randomization
• Active or history of malignancy within 5 years prior to randomization

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

L2 Diabetes Centre, Queen Mary Hospital

Hong Kong, Hong Kong

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Ketosis

Interventions

dapagliflozin; Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Acidosis; Acid-Base Imbalance

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Study Officials

• Kathryn Tan, MD

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2019
• First Posted: May 22, 2019
• Study Start: August 16, 2017
• Primary Completion: October 16, 2020
• Study Completion: October 16, 2020
• Last Updated: April 29, 2021

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)