Gliflozins and Cardiovascular Risk Factors in Type 2 Diabetes (GIOIA) (GIOIA)

Effects of Gliflozins on Markers of Cardiovascular Risk in Type 2 Diabetes (GIOIA): a Multicenter Pragmatic Prospective Cohort Study

GIOIA represents a multicenter pragmatic prospective cohort study, aimed at evaluating the effects of SGLT2 inhibitors currently marketed (dapagliflozin, canagliflozin, empagliflozin) on markers of vascular, myocardial and renal damage, in patients with type 2 diabetes not well controlled with metformin and/or basal insulin. The changes of the interest outcomes are compared with those obtained with a comparator glucose lowering class (DPP-4inhibitors) over a follow-up of two years.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: SGLT-2i; Drug: DPP-4i

• Study Type: Observational
• Enrollment (Actual): 1150

Contacts and Locations

Study Locations

• Italy
  • Campania
    • Naples, Campania, Italy, 80138
      • Unit of Diabetes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 31 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Men and women with type 2 diabetes attending diabetes centers of the Campanian county treated with metformin and/or basal insulin who start therapy with a SGLT-2i or DPP-4i according to the clinical practice.

Description

Inclusion Criteria:

• type 2 diabetes for at least 5 years
• new use of an SGLT2-I or DPP4-I as add-on to metformin or insulin according to clinical practice
• HbA1c levels ≥ 7% and ≤ 8.5%
• eGFR ≥ 60 ml/min/1.73 m2

Exclusion Criteria:

• Type 1 diabetes or secondary diabetes resulting from specific causes
• History of neurovascular ulcers
• Previous therapy with SGLT-2i or DPP4-i in the 3 months prior to the study enrollment
• History of cancer within the last 5 years
• Pregnancy or active breast-feeding
• Serum creatinine level ≥ 1.3 mg/dl in women and ≥ 1.4 mg/dl in men
• eGFR ≤ 60 ml/min/1.73 m2

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
SGLT-2i; Type 2 diabetic patients treated with metformin and/or insulin starting therapy with a SGLT-2 inhibitor: dapagliflozin 10 mg, oral, once daily or canagliflozin 100 mg, oral, daily or empagliflozin 10 mg, oral, daily	Drug: SGLT-2i; Dapagliflozin or canagliflozin or empagliflozin add on to metformin ± basal insulin
DPP-4i; Type 2 diabetic patients treated with metformin and/or insulin starting therapy with a DPP-4 inhibitor: sitagliptin 100 mg, oral once daily or vildagliptin 50 mg, oral, twice daily or saxaglitpin 5 mg, oral, once daily or linagliptin 5 mg, oral, once daily or alogliptin 25 mg, oral, once daily	Drug: DPP-4i; Sitagliptin or vildagliptin or saxagliptin or linagliptin or alogliptin add on to metformin ± basal insulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Carotid intima-media thickness (CIMT)	Progression (increase in mean CIMT in millimeters [mm]) or regression (reduction > o = 0.020 mm on mean CIMT) after 2 years of follow-up	24 months
Myocardial stiffness indexes	Change from baseline in: Left Ventricular Ejection Fraction (LVEF) in percentage (%), Diastolic Left Ventricular Dimension (LVDs) in centimeters (cm) Interventricular Septum thickness (IVS) in cm left vetricular posterior wall thickness (PWs) in cm	24 months
Urinary albumin to creatinine ratio excretion	Development of microalbuminuria in normoalbuminuric patients at baseline or development of macroalbuminuria in patients with microalbuminuria at baseline; regression of microalbuminuria to normoalbuminuria or regression of macroalbuminuria to microalbuminuria	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight	Change in body weight in kilograms (kg) from baseline	24 months
Body mass index (BMI)	Change in body mass index in Kg/mq from baseline	24 months
Waist circumference (WC)	Change in waist circumference in cm from baseline	24 months
Blood pressure	Change in systolic and dyastolic blood pressure in mmHg from baseline	24 months
estimated Glomerular filtration rate (eGFR)	Change in estimated glomerular filtration rate in mI/min/1.73 mq from baseline	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c	Change in HbA1c in % from baseline	24 months
Mean amplitude glucose excursions (MAGE)	Change in MAGE in mmol/L from baseline	24 months
Lipid profile	Change in total cholesterol, tryglicerides, HDL-cholesterol, and LDL-cholesterol in mg/dL from baseline	24 months

Collaborators and Investigators

• Sponsor: University of Campania "Luigi Vanvitelli"
• Investigators: Principal Investigator: Katherine Esposito, University of Campania "Luigi Vanvitelli"; Study Director: Dario Giugliano, University of Campania "Luigi Vanvitelli"

Publications and helpful links

General Publications

• Giugliano D, Maiorino MI, Longo M, Esposito K. Are gliflozins the new statins for diabetes? Diabetes Res Clin Pract. 2019 Jul;153:191-193. doi: 10.1016/j.diabres.2019.04.014. Epub 2019 Apr 5. No abstract available.
• Giugliano D, Maiorino MI, Bellastella G, Esposito K. Glycemic control in type 2 diabetes: from medication nonadherence to residual vascular risk. Endocrine. 2018 Jul;61(1):23-27. doi: 10.1007/s12020-017-1517-9. Epub 2018 Jan 10.
• Esposito K, Longo M, Maiorino MI, Petrizzo M, Gicchino M, Bellastella G, Giugliano D. Metabolic effectiveness of gliflozins and gliptins in the routine clinical practice of patients with type 2 diabetes: preliminary results from GIOIA, a prospective multicentre study. Diabetes Res Clin Pract. 2019 Sep;155:107787. doi: 10.1016/j.diabres.2019.107787. Epub 2019 Jul 19.
• Longo M, Scappaticcio L, Maiorino MI, De Nicola L, Bellastella G, Esposito K. Renal and metabolic effects of SGLT-2i and DPP-4i according to basal estimated glomerular filtration rate: Analysis from GIOIA, an observational prospective study. Diabetes Res Clin Pract. 2021 Aug;178:108990. doi: 10.1016/j.diabres.2021.108990. Epub 2021 Jul 29.
• Longo M, Caruso P, Scappaticcio L, Maiorino MI, Bellastella G, Capuano A, Esposito K, Giugliano D. Two years with GIOIA 'Effects of gliflozins and gliptins on markers of cardiovascular damage in type 2 diabetes': A prospective, multicentre, quasi-experimental study on sodium-glucose cotransporter 2 and dipeptidyl peptidase-4 inhibitors in diabetes clinical practice. Diabetes Obes Metab. 2024 Apr;26(4):1492-1501. doi: 10.1111/dom.15451. Epub 2024 Jan 17.

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2018
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: April 9, 2019
• First Submitted That Met QC Criteria: April 13, 2019
• First Posted (Actual): April 17, 2019

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 2193/2018

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: Yes
• Studies a U.S. FDA-regulated device product: No