Substitution of Sulfonylureas With New Generation of Hypoglycemic Drugs for the Treatment of Type 2 Diabetes Mellitus

NCT ID: NCT04272359

Last Updated: 2021-09-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

138 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-05-06

Study Completion Date

2021-12-31

Brief Summary

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This is a multicentric, prospective, parallel groups study. Patient recruitment will be carried out at the U.O. Departmental Endocrinology and Diabetology ASST FBF Sacco, Fatebenefratelli and Ophthalmic Hospital, and at the SSD of Endocrine Diseases and Diabetology ASST FBF Sacco, L. Sacco Hospital.

At the screening visit, patients being treated with sulfonylureas / glinids will be shifted, depending on the subject's biochemical and phenotypic characteristics, based on current prescribing criteria and diabetes complications, to one of 4 different types of treatment:

1. GROUP 1: SGLT2 inhibitors +/- Metformin
2. GROUP 2: DPP4 inhibitors +/- Metformin
3. GROUP 3: GLP1-RA + Long-acting insulin +/- Metformin
4. GROUP 4: SGLT2 inhibitors + DPP4 inhibitors +/- Metformin At the screening visit the clinician will evaluate which new treatment to assign to the patient, based on the subject's biochemical and phenotypic characteristics, current prescribing criteria and existing complications (Algorithm for the treatment of diabetes mellitus, SID-AMD Care Standard 2018)

Detailed Description

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Approximately 500 T2DM patients aged ≥18 years will be enrolled according to the guidelines of the American Diabetes Association (ADA) with poor glycemic control (hemoglobin A1c \[A1C\] ≥6.5% and ≤11% \[≥58 mmol / mol and ≤97 mmol / mol\]), in stabilized treatment with sulfonylureas / glinids, which meet all the study enrollment criteria.

During the study 7 visits are scheduled which coincide with the routine diabetic visits.

During the scheduled visits the patients of the study will be subjected to:

* Enrollment on the first visit if the inclusion criteria are met and those of exclusion are absent
* Anamnestic and clinical collection
* Evaluation of the type of treatment to which they have been assigned and possible modification of drug therapy in the in case that the desired glycemic target has not yet been reached up.

Conditions

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T2DM (Type 2 Diabetes Mellitus) Diet, Healthy Renal Function Disorder Albuminuria

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Group 1

SGLT2 inibitori +/- Metformin

Sulfa-zero: possible benefits of the treatment of new generation hypoglycaemic drugs compared to sulphonylureas

Intervention Type DRUG

Substitution of sulfonylureas with other classes of new hypoglycaemic drugs. In every group, it will be evaluated:

* efficacy in terms of glycometabolic compensation (glycemia, HbA1c, lipid profile);
* effects on BMI, blood pressure monitoring and hypoglycemic risk;
* changes in renal function and microalbuminuria;
* tolerability and side effects of the new therapeutic regimes;
* therapeutic adherence;
* post-prandial glycemic excursion, determined by a 6-point glycemic diary (pre- and 2h post-prandial glucose values) to be performed at home in the week before the scheduled follow-up visit;
* effects on chronic complications of diabetes and cardiovascular safety.

Group 2

DPP4 inibitori +/- Metformin

Sulfa-zero: possible benefits of the treatment of new generation hypoglycaemic drugs compared to sulphonylureas

Intervention Type DRUG

Substitution of sulfonylureas with other classes of new hypoglycaemic drugs. In every group, it will be evaluated:

* efficacy in terms of glycometabolic compensation (glycemia, HbA1c, lipid profile);
* effects on BMI, blood pressure monitoring and hypoglycemic risk;
* changes in renal function and microalbuminuria;
* tolerability and side effects of the new therapeutic regimes;
* therapeutic adherence;
* post-prandial glycemic excursion, determined by a 6-point glycemic diary (pre- and 2h post-prandial glucose values) to be performed at home in the week before the scheduled follow-up visit;
* effects on chronic complications of diabetes and cardiovascular safety.

Group 3

GLP1-RA + Long-Acting Insulin +/- Metformin

Sulfa-zero: possible benefits of the treatment of new generation hypoglycaemic drugs compared to sulphonylureas

Intervention Type DRUG

Substitution of sulfonylureas with other classes of new hypoglycaemic drugs. In every group, it will be evaluated:

* efficacy in terms of glycometabolic compensation (glycemia, HbA1c, lipid profile);
* effects on BMI, blood pressure monitoring and hypoglycemic risk;
* changes in renal function and microalbuminuria;
* tolerability and side effects of the new therapeutic regimes;
* therapeutic adherence;
* post-prandial glycemic excursion, determined by a 6-point glycemic diary (pre- and 2h post-prandial glucose values) to be performed at home in the week before the scheduled follow-up visit;
* effects on chronic complications of diabetes and cardiovascular safety.

Group 4

SGLT2 inibitori + DPP4 inibitori +/- Metformin

Sulfa-zero: possible benefits of the treatment of new generation hypoglycaemic drugs compared to sulphonylureas

Intervention Type DRUG

Substitution of sulfonylureas with other classes of new hypoglycaemic drugs. In every group, it will be evaluated:

* efficacy in terms of glycometabolic compensation (glycemia, HbA1c, lipid profile);
* effects on BMI, blood pressure monitoring and hypoglycemic risk;
* changes in renal function and microalbuminuria;
* tolerability and side effects of the new therapeutic regimes;
* therapeutic adherence;
* post-prandial glycemic excursion, determined by a 6-point glycemic diary (pre- and 2h post-prandial glucose values) to be performed at home in the week before the scheduled follow-up visit;
* effects on chronic complications of diabetes and cardiovascular safety.

Interventions

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Sulfa-zero: possible benefits of the treatment of new generation hypoglycaemic drugs compared to sulphonylureas

Substitution of sulfonylureas with other classes of new hypoglycaemic drugs. In every group, it will be evaluated:

* efficacy in terms of glycometabolic compensation (glycemia, HbA1c, lipid profile);
* effects on BMI, blood pressure monitoring and hypoglycemic risk;
* changes in renal function and microalbuminuria;
* tolerability and side effects of the new therapeutic regimes;
* therapeutic adherence;
* post-prandial glycemic excursion, determined by a 6-point glycemic diary (pre- and 2h post-prandial glucose values) to be performed at home in the week before the scheduled follow-up visit;
* effects on chronic complications of diabetes and cardiovascular safety.

Intervention Type DRUG

Other Intervention Names

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Shift to new generation therapeutic regimens

Eligibility Criteria

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Inclusion Criteria

* Age over 18 years;
* 6.5% \<HbA1c \<11%;
* Diagnosis of type 2 diabetes mellitus;
* Active treatment with sulfonylureas / glinids, both in monotherapy and in association with other long-acting hypoglycemic / insulins.
* Written informed consent of the patient or a legal guardian signed and dated

Exclusion Criteria

* Patients suffering from severe systemic diseases, fever, known chronic inflammatory states
* PCR determinants\> 10 mg/L;
* HbA1c\> 11% or HbA1c \<6.5%;
* Use of corticosteroids at the time of enrollment;
* Poor patient understanding of spoken and written Italian;
* Absent compliance.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Milan

OTHER

Sponsor Role lead

Responsible Party

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Paolo Fiorina, MD

Clinical Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Paolo Fiorina, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Milan

Locations

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ASST FBF-Sacco P.O. Sacco/Fatebenefratelli e Oftalmico

Milan, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Maria Elena Lunati, MD

Role: CONTACT

02 63632256

Teresa Letizia, Dr.

Role: CONTACT

02 39042648

Facility Contacts

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Teresa Letizia

Role: primary

References

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Garber A, Henry R, Ratner R, Garcia-Hernandez PA, Rodriguez-Pattzi H, Olvera-Alvarez I, Hale PM, Zdravkovic M, Bode B; LEAD-3 (Mono) Study Group. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet. 2009 Feb 7;373(9662):473-81. doi: 10.1016/S0140-6736(08)61246-5. Epub 2008 Sep 24.

Reference Type BACKGROUND
PMID: 18819705 (View on PubMed)

Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP, Kravitz BG, Lachin JM, O'Neill MC, Zinman B, Viberti G; ADOPT Study Group. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006 Dec 7;355(23):2427-43. doi: 10.1056/NEJMoa066224. Epub 2006 Dec 4.

Reference Type BACKGROUND
PMID: 17145742 (View on PubMed)

Zhang Y, Hong J, Chi J, Gu W, Ning G, Wang W. Head-to-head comparison of dipeptidyl peptidase-IV inhibitors and sulfonylureas - a meta-analysis from randomized clinical trials. Diabetes Metab Res Rev. 2014 Mar;30(3):241-56. doi: 10.1002/dmrr.2482.

Reference Type BACKGROUND
PMID: 24123720 (View on PubMed)

Charbonnel B, Schernthaner G, Brunetti P, Matthews DR, Urquhart R, Tan MH, Hanefeld M. Long-term efficacy and tolerability of add-on pioglitazone therapy to failing monotherapy compared with addition of gliclazide or metformin in patients with type 2 diabetes. Diabetologia. 2005 Jun;48(6):1093-104. doi: 10.1007/s00125-005-1751-1. Epub 2005 May 12.

Reference Type BACKGROUND
PMID: 15889234 (View on PubMed)

Matthews DR, Charbonnel BH, Hanefeld M, Brunetti P, Schernthaner G. Long-term therapy with addition of pioglitazone to metformin compared with the addition of gliclazide to metformin in patients with type 2 diabetes: a randomized, comparative study. Diabetes Metab Res Rev. 2005 Mar-Apr;21(2):167-74. doi: 10.1002/dmrr.478.

Reference Type BACKGROUND
PMID: 15386821 (View on PubMed)

Nauck M, Frid A, Hermansen K, Thomsen AB, During M, Shah N, Tankova T, Mitha I, Matthews DR. Long-term efficacy and safety comparison of liraglutide, glimepiride and placebo, all in combination with metformin in type 2 diabetes: 2-year results from the LEAD-2 study. Diabetes Obes Metab. 2013 Mar;15(3):204-12. doi: 10.1111/dom.12012. Epub 2012 Oct 11.

Reference Type BACKGROUND
PMID: 22985213 (View on PubMed)

Cefalu WT, Leiter LA, Yoon KH, Arias P, Niskanen L, Xie J, Balis DA, Canovatchel W, Meininger G. Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet. 2013 Sep 14;382(9896):941-50. doi: 10.1016/S0140-6736(13)60683-2. Epub 2013 Jul 12.

Reference Type BACKGROUND
PMID: 23850055 (View on PubMed)

Nauck MA. Incretin-based therapies for type 2 diabetes mellitus: properties, functions, and clinical implications. Am J Med. 2011 Jan;124(1 Suppl):S3-18. doi: 10.1016/j.amjmed.2010.11.002.

Reference Type BACKGROUND
PMID: 21194578 (View on PubMed)

Del Prato S, Nauck M, Duran-Garcia S, Maffei L, Rohwedder K, Theuerkauf A, Parikh S. Long-term glycaemic response and tolerability of dapagliflozin versus a sulphonylurea as add-on therapy to metformin in patients with type 2 diabetes: 4-year data. Diabetes Obes Metab. 2015 Jun;17(6):581-590. doi: 10.1111/dom.12459. Epub 2015 Apr 6.

Reference Type BACKGROUND
PMID: 25735400 (View on PubMed)

Nauck MA. Update on developments with SGLT2 inhibitors in the management of type 2 diabetes. Drug Des Devel Ther. 2014 Sep 11;8:1335-80. doi: 10.2147/DDDT.S50773. eCollection 2014.

Reference Type BACKGROUND
PMID: 25246775 (View on PubMed)

Ridderstrale M, Andersen KR, Zeller C, Kim G, Woerle HJ, Broedl UC; EMPA-REG H2H-SU trial investigators. Comparison of empagliflozin and glimepiride as add-on to metformin in patients with type 2 diabetes: a 104-week randomised, active-controlled, double-blind, phase 3 trial. Lancet Diabetes Endocrinol. 2014 Sep;2(9):691-700. doi: 10.1016/S2213-8587(14)70120-2. Epub 2014 Jun 16.

Reference Type BACKGROUND
PMID: 24948511 (View on PubMed)

Maedler K, Carr RD, Bosco D, Zuellig RA, Berney T, Donath MY. Sulfonylurea induced beta-cell apoptosis in cultured human islets. J Clin Endocrinol Metab. 2005 Jan;90(1):501-6. doi: 10.1210/jc.2004-0699. Epub 2004 Oct 13.

Reference Type BACKGROUND
PMID: 15483097 (View on PubMed)

Karl DM, Gill J, Zhou R, Riddle MC. Clinical predictors of risk of hypoglycaemia during addition and titration of insulin glargine for type 2 diabetes mellitus. Diabetes Obes Metab. 2013 Jul;15(7):622-8. doi: 10.1111/dom.12072. Epub 2013 Feb 24.

Reference Type BACKGROUND
PMID: 23350795 (View on PubMed)

Holstein A, Plaschke A, Egberts EH. Lower incidence of severe hypoglycaemia in patients with type 2 diabetes treated with glimepiride versus glibenclamide. Diabetes Metab Res Rev. 2001 Nov-Dec;17(6):467-73. doi: 10.1002/dmrr.235.

Reference Type BACKGROUND
PMID: 11757083 (View on PubMed)

A study of the effects of hypoglycemia agents on vascular complications in patients with adult-onset diabetes. VI. Supplementary report on nonfatal events in patients treated with tolbutamide. Diabetes. 1976 Dec;25(12):1129-53. doi: 10.2337/diab.25.12.1129. No abstract available.

Reference Type BACKGROUND
PMID: 992232 (View on PubMed)

Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):837-53.

Reference Type BACKGROUND
PMID: 9742976 (View on PubMed)

Nunes AP, Iglay K, Radican L, Engel SS, Yang J, Doherty MC, Dore DD. Hypoglycaemia seriousness and weight gain as determinants of cardiovascular disease outcomes among sulfonylurea users. Diabetes Obes Metab. 2017 Oct;19(10):1425-1435. doi: 10.1111/dom.13000. Epub 2017 Jul 21.

Reference Type BACKGROUND
PMID: 28497592 (View on PubMed)

Middleton TL, Wong J, Molyneaux L, Brooks BA, Yue DK, Twigg SM, Wu T. Cardiac Effects of Sulfonylurea-Related Hypoglycemia. Diabetes Care. 2017 May;40(5):663-670. doi: 10.2337/dc16-1972. Epub 2017 Feb 21.

Reference Type BACKGROUND
PMID: 28223296 (View on PubMed)

Other Identifiers

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Sacco Milan

Identifier Type: -

Identifier Source: org_study_id

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