SGLT-2 and DPP-4 Inhibition, Subclinical Inflammation of the Genito-urinary Tract and Risk of Infections.

NCT04735042 | Completed DMC

• 1 other identifier: AS0005
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

In this observational study, 60 subjects with type 2 diabetes (T2D) and eligible, as per good clinical practice, for therapy with SGLT-2 inhibitor, will be randomized to receive a SGLT-2 inhibitor or a fixed dose combination of SGLT-2 inhibitor with a DPP4-inihibitor for 12 weeks. Measures will be performed at baseline and after 12 weeks of treatment, as per good clinical practice.

Conditions

Type 2 Diabetes; Urinary Tract Infections

Keywords

UTI; Type 2 Diabetes; SGLT2 inhibitors; DPP4 inhibitors

Outcome Measures

Primary Outcomes (2)

• Change from Baseline in metagenomic analysis based on rRNA 16S gene

  Metagenomic analysis based on rRNA 16S gene will be performed by Novogene on Illumina platform (Hong Kong, China)

  Each patients will be analyzed at baseline and after 12 weeks

• Change from Baseline of total bacterial load

  Absolute quantification of total bacterial load in the original sample using real-Time quantitative PCR

  Each patients will be analyzed at baseline and after 12 weeks

Secondary Outcomes (7)

• Fasting glucose

  baseline and 12 week

• Glycated Haemoglobin

  baseline and 12 week

• Renal function

  baseline and 12 week

• Albumin excretion

  baseline and 12 week

• Total cholesterol

  baseline and 12 week

Study Arms (2)

SGLT2 and DPP-4 inhibitors

Patients undergoing SGLT2i and DPP4i.

Drug: Empagliflozin / Linagliptin or Dapagliflozin/Saxagliptin Pill

SGLT2 inhibitors only

Patients undergoing SGLT2i alone.

Drug: Empagliflozin or Dapagliflozin Pill

Interventions

Empagliflozin / Linagliptin or Dapagliflozin/Saxagliptin Pill DRUG

association between SGLT2-inhibitor and DPP4-inhibitor

Also known as: Glyxambi or Qtern

SGLT2 and DPP-4 inhibitors

Empagliflozin or Dapagliflozin Pill DRUG

SGLT2-inhibitor: diabetic oral drug with diuretic properties.

Also known as: Jardiance or Forxiga

SGLT2 inhibitors only

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study will consecutively enrolled 60 patients among those referring to the Departiment of Diabetes and Metabolic disease, Santa Chiara Hospital, Pisa.

You may qualify if:

• Type 2 diabetes diagnosis
• Hb1Ac ≥ 7% and ≤ 9%

You may not qualify if:

• Hb1Ac \> 9%
• current treatment with an SGLT2i or a DPP4i drugs, or in the prior 4 week
• irritating and/or obstructive urinary or genital symptoms
• menstrual cycle for women
• current antibiotic treatment or in the prior 4 weeks
• anatomical or functional abnormalities of the urinary tract (e.g. incontinence, neurological bladder, bladder prolapse).

Sponsors & Collaborators

• University of Pisa: lead

Study Sites (1)

University of Pisa

Pisa, Pisa, 56125, Italy

Location

Related Publications (12)

• Nitzan O, Elias M, Chazan B, Saliba W. Urinary tract infections in patients with type 2 diabetes mellitus: review of prevalence, diagnosis, and management. Diabetes Metab Syndr Obes. 2015 Feb 26;8:129-36. doi: 10.2147/DMSO.S51792. eCollection 2015.

  PMID: 25759592 BACKGROUND

• Renko M, Tapanainen P, Tossavainen P, Pokka T, Uhari M. Meta-analysis of the significance of asymptomatic bacteriuria in diabetes. Diabetes Care. 2011 Jan;34(1):230-5. doi: 10.2337/dc10-0421. Epub 2010 Oct 11.

  PMID: 20937688 BACKGROUND

• Schmiemann G, Kniehl E, Gebhardt K, Matejczyk MM, Hummers-Pradier E. The diagnosis of urinary tract infection: a systematic review. Dtsch Arztebl Int. 2010 May;107(21):361-7. doi: 10.3238/arztebl.2010.0361. Epub 2010 May 28.

  PMID: 20539810 BACKGROUND

• He K, Hu Y, Shi JC, Zhu YQ, Mao XM. Prevalence, risk factors and microorganisms of urinary tract infections in patients with type 2 diabetes mellitus: a retrospective study in China. Ther Clin Risk Manag. 2018 Feb 26;14:403-408. doi: 10.2147/TCRM.S147078. eCollection 2018.

  PMID: 29520146 BACKGROUND

• Aswani SM, Chandrashekar U, Shivashankara K, Pruthvi B. Clinical profile of urinary tract infections in diabetics and non-diabetics. Australas Med J. 2014 Jan 31;7(1):29-34. doi: 10.4066/AMJ.2014.1906. eCollection 2014.

  PMID: 24567764 BACKGROUND

• Masajtis-Zagajewska A, Nowicki M. New markers of urinary tract infection. Clin Chim Acta. 2017 Aug;471:286-291. doi: 10.1016/j.cca.2017.06.003. Epub 2017 Jun 13.

  PMID: 28622967 BACKGROUND

• Liu J, Li L, Li S, Jia P, Deng K, Chen W, Sun X. Effects of SGLT2 inhibitors on UTIs and genital infections in type 2 diabetes mellitus: a systematic review and meta-analysis. Sci Rep. 2017 Jun 6;7(1):2824. doi: 10.1038/s41598-017-02733-w.

  PMID: 28588220 BACKGROUND

• Li D, Wang T, Shen S, Fang Z, Dong Y, Tang H. Urinary tract and genital infections in patients with type 2 diabetes treated with sodium-glucose co-transporter 2 inhibitors: A meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2017 Mar;19(3):348-355. doi: 10.1111/dom.12825. Epub 2016 Dec 19.

  PMID: 27862830 BACKGROUND

• Yu H, Woo VC. Emerging use of combination therapies for the management of type 2 diabetes - focus on saxagliptin and dapagliflozin. Diabetes Metab Syndr Obes. 2017 Jul 21;10:317-332. doi: 10.2147/DMSO.S117982. eCollection 2017.

  PMID: 28769579 BACKGROUND

• Del Prato S, Rosenstock J, Garcia-Sanchez R, Iqbal N, Hansen L, Johnsson E, Chen H, Mathieu C. Safety and tolerability of dapagliflozin, saxagliptin and metformin in combination: Post-hoc analysis of concomitant add-on versus sequential add-on to metformin and of triple versus dual therapy with metformin. Diabetes Obes Metab. 2018 Jun;20(6):1542-1546. doi: 10.1111/dom.13258. Epub 2018 Mar 25.

  PMID: 29446523 BACKGROUND

• Kim NH, Yu T, Lee DH. The nonglycemic actions of dipeptidyl peptidase-4 inhibitors. Biomed Res Int. 2014;2014:368703. doi: 10.1155/2014/368703. Epub 2014 Jul 21.

  PMID: 25140306 BACKGROUND

• Lewis DA, Brown R, Williams J, White P, Jacobson SK, Marchesi JR, Drake MJ. The human urinary microbiome; bacterial DNA in voided urine of asymptomatic adults. Front Cell Infect Microbiol. 2013 Aug 15;3:41. doi: 10.3389/fcimb.2013.00041. eCollection 2013.

  PMID: 23967406 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum Urine

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Urinary Tract Infections

Interventions

empagliflozin; Linagliptin; dapagliflozin; saxagliptin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinazolines

Study Officials

• Anna Solini, MD, PhD

  University of Pisa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 22, 2021
• First Posted: February 2, 2021
• Study Start: October 7, 2020
• Primary Completion: October 7, 2021
• Study Completion: April 7, 2022
• Last Updated: July 18, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)