Comparative Effectiveness of Dapagliflozin Versus DPP-4 Inhibitors

Sponsor
University of Padova
Study ID
NCT04304430
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 80 Years
Healthy Volunteers
Not accepted

Interventions

  • Dapagliflozin — DRUG
    Initiation of dapagliflozin according to clinical indication
  • DPP-4 inhibitor — DRUG
    Initiation of DPP-4i according to clinical indication

Study Details

Owing to their glycemic and extraglycemic effects, sodium glucose cotransporter-2 inhibitors (SGLT2i) are becoming ideal second-line agents for the treatment of type 2 diabetes (T2D). However, SGLT2i are not devoid of side effects. Because of glycosuria, SGLT2i increase the risk of genito-urinary tract infections (GUTI) and may favour dehydration or volume depletion, especially in patients taking diuretics. In addition, SGLT2i can precipitate diabetic ketoacidosis (DKA), especially when used off-label in type 1 diabetes or in T2D patients with poor beta cell function. Furthermore, based on final results of the cardiovascular outcome trials, a boxed warning was added to the canagliflozin label regarding an increase in the risk of amputations. For these reasons, although the cardiovascular benefits of SGLT2i are clearly delineating, their widespread use as second-line agents may be contended by other oral glucose lowering medications which are perceived to be provided with a more neutral safety profile, namely dipeptidyl peptidase-4 (DPP-4) inhibitors (DPP-4i). DPP-4i as a class lower HbA1c by 0.5-0.7% and exert minor or no effects on body weight, blood pressure, and lipid profile. In addition, three large randomized controlled trials (RCTs) showed no benefit of sitagliptin, saxagliptin, and alogliptin on cardiovascular outcomes, with an isolated signal that saxagliptin might increase the risk of hospitalization for heart failure. Importantly, observational retrospective studies has shown that the SGLT2i dapagliflozin, compared to DPP4i, is associated with lower risk of cardiovascular events and all-cause mortality. The present study aims at providing real world data on the comparative effectiveness of SGLT2i versus DPP-4i on a composite endpoint of HbA1c, body weight and blood pressure reduction. The study has the potential to demonstrate multiple benefits of SGLT2i in the routine clinical practice, as compared to DPP-4i, which are perceived to be safer but are mostly devoid of extraglycemic effects. We hypothesize that dapagliflozin is superior to DPP-4i in the attainment of a composite endpoint of HbA1c, body weight and blood pressure reduction.

Key Dates

Start date
Oct 18, 2018
Status verified
Mar 2020
Primary completion
Dec 26, 2019
Completion
Feb 29, 2020

Study Design

Enrollment
11,206 participants (actual)

Arms

  • Arm: Dapagliflozin
    Patients who initiated a new therapy with dapagliflozin
  • Arm: DPP-4i
    Patients who initiated a new therapy with a DPP-4i

Primary Outcome Measure

Combined categorized endpoint [ Time Frame: 3-12 months ]

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