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

• Status: Completed
• Trial end date: 2020-10-16
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The University of Hong Kong
• Treatments: 2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol; Dapagliflozin; Sitagliptin Phosphate

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

• Hospitalization for acute illness within 3 months prior to randomization

• Severe mental disorder

• Unable to understand written patient information and to give informed consent

• Ongoing participation in other clinical intervention trials

• Other unspecified concomitant conditions that deemed unsuitable for study participation upon professional judgments by principal investigators