Comparative Effectiveness of Dapagliflozin Versus DPP-4 Inhibitors

NCT04304430 | Completed

• 1 other identifier: 4356/AO/17
• Study Type: observational
• Target: 11,206
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Combined categorized endpoint

  Percentage of patients achieving the following composite endpoint in the two groups: reduction of HbA1c ≥0.5% and reduction of body weight ≥2 kg and reduction of systolic blood pressure ≥2 mmHg.

  3-12 months

Secondary Outcomes (7)

• Combined endpoint

  3-12 months

• Change in HbA1c

  3-12 months

• Change in body weight

  3-12 months

• Change in systolic blood pressure

  3-12 months

• Proportion of patients attaining HbA1c target

  3-12 months

Study Arms (2)

Dapagliflozin

Patients who initiated a new therapy with dapagliflozin

Drug: Dapagliflozin

DPP-4i

Patients who initiated a new therapy with a DPP-4i

Drug: DPP-4 inhibitor

Interventions

Dapagliflozin DRUG

Initiation of dapagliflozin according to clinical indication

Dapagliflozin

DPP-4 inhibitor DRUG

Initiation of DPP-4i according to clinical indication

DPP-4i

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with type 2 diabetes attending diabetes specialist outpatient clinics

You may qualify if:

• Diagnosis of type 2 diabetes;
• Age 18-80\*;
• Disease duration \>1 year;
• Initiation of dapagliflozin/DPP-4i in association with metformin and/or insulin.

You may not qualify if:

• Type 1 diabetes;
• Age \<18 or \>80\*;
• Previous or ongoing therapy with another SGLT2i;
• CKD (eGFR \<60 ml/min/1.73 mq)

Sponsors & Collaborators

• University of Padova: lead

Study Sites (1)

University Hospital of Padova

Padua, 35128, Italy

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

dapagliflozin; Dipeptidyl-Peptidase IV Inhibitors

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2020
• First Posted: March 11, 2020
• Study Start: October 18, 2018
• Primary Completion: December 26, 2019
• Study Completion: February 29, 2020
• Last Updated: March 11, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)