Managing DIabetes Remission After Combined Therapy in EarLy Stage of DiabetEs

NCT04271189 | Completed Phase 3

• 1 other identifier: 2018-833-12
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

Epidemiologic, social and economic burdens of type 2 diabetes mellitus (T2DM) keep rising worldwide. Implementation of T2DM preventive trategies is lagging behind. Metabolic surgery, very low calorie diet can induce T2DM remission, but so far for few patients. The investigators will assess the efficacy to cause T2DM remission (primary end point) and direct costs to the National Health System of a 4-month polychemotherapy (metformin+pioglitazone+sitagliptin+empagliflozin) regimen vs standard care in patients with newly diagnosed T2DM by an open label, pragmatic RCT. Mechanisms of action will be investigated in a sub-cohort by a prolonged OGTT plus dual tracer technique and modeling of beta cell function. If proved efficacious in this proof-of-concept study and inducer of durable remission in the future, T2DM polychemotherapy will turn out to be a convenient, relatively unexpensive strategy to restrain prevalence of T2DM and its complications and to alleviate its personal, social and economic burden.

Conditions

Newly Diagnosed Type 2 Diabetes

Keywords

Type 2 diabetes; Polychemotherapy; Diabetes remission

Outcome Measures

Primary Outcomes (1)

• Assess the T2DM remission rate in patients with newly diagnosed T2DM treated with either POLYCHEM or with SDC for 16 weeks.

  Remission was defined as HbA1c \<6.5% or 48mmol/mol for at least 12 weeks without pharmacologic or surgical treatment for diabetes.

  12 weeks after the end of treatment

Secondary Outcomes (9)

• Assess the proportion of complete T2DM remission rate in the 2 groups

  12 weeks after the end of treatment

• Monitor the quality of life EQ-5D-DL

  0, 16, 28 weeks

• Monitor the quality of life ADDQOL

  0, 16, 28 weeks

• Monitor the costs of National Health System service utilization

  0, 16, 28 weeks

• Quantify the effects of either POLYCHEM or SDC on the main determinants of glucose regulation

  0, 16, 28 weeks

Study Arms (2)

POLYCHEM

EXPERIMENTAL

Metformin (extended release), Pioglitazone, Sitagliptin and Empaglifozin.

Drug: Metformin-Sitagliptin-Empaglifozin-Pioglitazone

STANDARD CARE

ACTIVE COMPARATOR

Standard of care according to the local health service.

Drug: Standard of care

Interventions

Metformin-Sitagliptin-Empaglifozin-Pioglitazone DRUG

1000 mg metformin (extended release) b.i.d., pioglitazone 15 mg b.i.d., sitagliptin 100 mg q.d., empaglifozin 10 mg q.d..

Also known as: POLYCHEM

POLYCHEM

Standard of care DRUG

Usual medical care to treat diabetes.

Also known as: SDC

STANDARD CARE

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 35-75 years;
• HbA1c \<= 10.0% (86 mmol/mol);
• T2DM diagnosis (\< 6 months)
• BMI\>=23 and \<=40 kg/m2
• Fasting C-peptide \> 0.3 nmol/l;
• GAD-antibody negative.

You may not qualify if:

• Diagnosis of type 1 diabetes;
• History of cancer in the previous 5 years;
• Multiple daily insulin treatment;
• Acute cardiovascular event within the previous 6 months;
• Chronic heart failure;
• eGFR \< 45 ml.min-1.1.73 m2 according to the MDRD formula;
• Women of child bearing potential with no use of acceptable contraception;
• Presence of diabetic retinopathy;
• Contraindications to the use of any drug of POLYCHEM.

Sponsors & Collaborators

• Azienda Ospedaliero-Universitaria di Parma: lead

Study Sites (1)

Azienda Ospedaliero Universitaria di Parma

Parma, Parma, 43126, Italy

Location

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MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Riccardo Bonadonna, MD

  Azienda Ospedaliero-Universitaria di Parma

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Endocrinology Unit

Model Details: Multicenter, open label pragmatic phase IIb/III RCT with a duration of 3 years

Study Record Dates

• First Submitted: October 15, 2019
• First Posted: February 17, 2020
• Study Start: September 1, 2020
• Primary Completion: August 31, 2024
• Study Completion: December 31, 2024
• Last Updated: March 18, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)