Newly Diagnosed Type 2 DiabetesPhase 3MIRACLENCT04271189
Managing DIabetes Remission After Combined Therapy in EarLy Stage of DiabetEs
A Phase 3 study testing Metformin-Sitagliptin-Empaglifozin-Pioglitazone in people with Newly Diagnosed Type 2 Diabetes, run by Azienda Ospedaliero-Universitaria di Parma at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 35 to 75 years
- Conditions the study is for
- Newly Diagnosed Type 2 Diabetes
- What is being tested?
- Metformin-Sitagliptin-Empaglifozin-Pioglitazone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 108 participants
- Where
- 1 siteItaly
- Study dates
- 1 Sep 2020to 31 Dec 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
Show all 9Show fewer
- Women of child bearing potential with no use of acceptable contraception;
- Presence of diabetic retinopathy;
- Contraindications to the use of any drug of POLYCHEM.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Prospective, Randomized, Parallel-group, Adaptive Design Phase IIb/III, Multicenter Study, to Assess the Efficacy of Polychemotherapy for Inducing Remission of Newly Diagnosed Type 2 Diabetes.
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.
Read the detailed description
Hypothesis: at diagnosis of T2DM, a 4 month course of oral polychemotherapy (POLYCHEM), by engaging multiple glucose lowering mechanisms, results into euglycemia and, after suspension, in T2DM remission in a clinically significant higher number of patients when compared to standard diabetes care (SDC).
- Diabetes remission: simultaneous nondiabetic values of fasting glucose, 2-hour glucose (after OGTT) and HbA1c for at least 12 months with no pharmacologic/surgical treatment of diabetes.
- Complete remission: all values of fasting glucose, 2-hour glucose and HbA1c are within the limits of normal glucose regulation; otherwise, remission is partial.
- Hyperglycemia remission as in diabetes remission, but duration<12 months.
Based on the "Consensus Report: Definition and Interpretation of Remission in Type 2 Diabetes" published on Diabetes Care 2021;44(10):2438-2444, remission should be defined as a return of HbA1c to <6.5% (<48 mmol/mol) that occurs spontaneously or following an intervention and that persists for at least 3 months in the absence of usual glucose-lowering pharmacotherapy.
A POLYCHEM (metformin, pioglitazone, sitagliptin and empagliflozin) will be used to improve:
- Insulin sensitivity of endogenous glucose output (EGO) and peripheral (muscle) glucose uptake (PGU);
- Beta cell function;
- GLP-1 and GIP bioavailability. To these effects, the direct glycosuric action of EMPA is added; EMPA effects on alpha cell and liver (increased glucagon secretion and EGO), may be, at least in part, counterbalanced by SITA and MET/PIO, respectively. Increased heart failure events with PIO may be, at least in part, counteracted by EMPA.
In many patients POLYCHEM should result in stable euglycemia, with negligible risk of hypoglycemia, and the number of patients in T2DM remission should be much higher than with MET+SU. The underpinning is that euglycemia reverses the detrimental effects of glucose toxicity and glucose regulation can be maintained in the nondiabetic range.
If the invesigators hypothesis is proved, POLYCHEM would be a convenient, simple and relatively unexpensive strategy to induce remission in a great number of patients with newly diagnosed T2DM. Novel, more efficacious goals of therapy could be introduced. Duration of remission is expected to delay the processes which result into the T2DM related risk of tissue damage. At the patient acceptance level, the trade off between the full T2DM burden (diabetes, its care and the risk of its complications) and the risk of T2DM relapse should favor the latter. At the society level, achieving a durable remission in a substantial number of these patients should attenuate, or even annull, the rises in prevalence, burden and tolls of "active" T2DM.
Patients with newly diagnosed (i.e. less than 6 months) T2DM will be recruited in the Diabetes Outpatient Clinics and will provide informed written consent before participation. After a screening visit (V0), patients will be randomized 1:1, with center stratification through web-based data collection (eCRF), to receive POLYCHEM or SDC with standard lifestyle intervention in both.
In both arms, patients will undergo planned visits at week 0 (V1), week 16 (V2), and week 28 (V3), after at least 3 days of drug washout. Patients will perform weekly a 6-point home blood glucose profile. Between week 17 and week 28, if a patient in hyperglycemia remission relapses, V3 will be anticipated (V3B), after which the patient will be treated as in SDC and will be re-evaluated at week 28 .
Visit procedures:
- V0: assessment of patient eligibility , including medical history, physical examination, and lab exams, if needed.
- V0S: between V0 and V1; signature of informed written consent and randomization.
- V1, V2, V3 and V3B: assessment of anthropometry, ambulatory blood pressure and heart rate, WBC, fasting glucose, HbA1c, lipids, AST, ALT, creatinine, lipase, urine analysis, microalbuminuria, insulin, C-peptide, glucagon, GLP-1, GIP, quality of life (QoL), and, only in V1, blood for DNA collection (the last for post hoc studies).
POLYCHEM-ARM: After V1, patients will start POLYCHEM (MET titrated to 1000 mg b.i.d., PIO 15 mg b.i.d., SITA 100 mg q.d., EMPA 10 mg q.d.) for 16 weeks, at the end of which (V2) patients in hyperglycemia remission stop drug therapy, the others are transferred to SDC. Patients with MET intolerance will be treated with PIO+SITA+EMPA only.
SDC-ARM: After V1, patients will continue their SDC for 16 weeks, at the end of which (V2) patients in hyperglycemia remission stop drug therapy, the others continue SDC.
- Conditions
- Newly Diagnosed Type 2 Diabetes
- Being tested
- Metformin-Sitagliptin-Empaglifozin-Pioglitazone, Standard of care
- Keywords
- Type 2 diabetes, Polychemotherapy, Diabetes remission
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin-Sitagliptin-Empaglifozin-PioglitazoneDrug
Also called POLYCHEM
1000 mg metformin (extended release) b.i.d., pioglitazone 15 mg b.i.d., sitagliptin 100 mg q.d., empaglifozin 10 mg q.d..
Standard of careDrug
Also called SDC
Usual medical care to treat diabetes.
| Study group | Role | What they receive |
|---|---|---|
| POLYCHEM | Experimental | Metformin (extended release), Pioglitazone, Sitagliptin and Empaglifozin. Receives: Drug: Metformin-Sitagliptin-Empaglifozin-Pioglitazone |
| STANDARD CARE | Active comparator | Standard of care according to the local health service. Receives: Drug: Standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks after the end of treatment
Secondary outcomes (9)
Assess the proportion of complete T2DM remission rate in the 2 groups
Normal measures of glucose metabolism (fasting glucose and HbA1c in normal range), for at least 12weeks without pharmacologic or surgical treatment for diabetes.
Measured: 12 weeks after the end of treatment
Monitor the quality of life EQ-5D-DL
Will be monitored through EQ-5D-DL questionnaires.
Measured: 0, 16, 28 weeks
Monitor the quality of life ADDQOL
QoL will be monitored through ADDQOL questionnaires.
Measured: 0, 16, 28 weeks
Monitor the costs of National Health System service utilization
All accesses to the National Healthcare System resources by each patient (visits, treatments, supplies, hospital admissions, etc.) will be retrieved from the Regional Health Registries and recorded. Costs will be assessed from a public purchaser perspective. For this reason all costs will refer to the reimbursement provided to the health facilities by the national health system.
Measured: 0, 16, 28 weeks
Quantify the effects of either POLYCHEM or SDC on the main determinants of glucose regulation
In all patients C-peptide will be used to compute static surrogate indexes of insulin sensitivity and beta cell function.
Measured: 0, 16, 28 weeks
Quantify the effects of either POLYCHEM or SDC on the main determinants of glucose regulation
In all patients insulin values will be used to compute static surrogate indexes of insulin sensitivity and beta cell function.
Measured: 0, 16, 28 weeks
Quantify the effects of either POLYCHEM or SDC on the main determinants of glucose regulation
Glucagon values will provide indexes of alpha cell function and of gut K- and L-cell function. Their role in predicting and/or explaining T2DM remission and/or relapse will be assessed.
Measured: 0, 16, 28 weeks
Quantify the effects of either POLYCHEM or SDC on the main determinants of glucose regulation
GLP-1 values will provide indexes of alpha cell function and of gut K- and L-cell function. Their role in predicting and/or explaining T2DM remission and/or relapse will be assessed.
Measured: 0, 16, 28 weeks
Quantify the effects of either POLYCHEM or SDC on the main determinants of glucose regulation
GIP values will provide indexes of alpha cell function and of gut K- and L-cell function. Their role in predicting and/or explaining T2DM remission and/or relapse will be assessed.
Measured: 0, 16, 28 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2020
- Study start1 Sep 2020
- Primary completion31 Aug 2024
- Study completion31 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (32)Papers the sponsor has linked to this study.
- Other trials for Newly Diagnosed Type 2 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multicenter, open label pragmatic phase IIb/III RCT with a duration of 3 years
- Masking
- None (open label)
- Enrolment
- 108 participants (actual)
Sponsor and investigators
- Lead sponsor
- Azienda Ospedaliero-Universitaria di Parma
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Riccardo Bonadonna, Azienda Ospedaliero-Universitaria di Parma
- Investigators
- Riccardo Bonadonna, MD, Principal investigator, Azienda Ospedaliero-Universitaria di Parma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04271189
- Sponsor's protocol ID
- 2018-833-12
- Acronym
- MIRACLE
- Status last verified
- Mar 2025
- First submitted
- 15 Oct 2019
- Last updated
- 18 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gregg EW, Li Y, Wang J, Burrows NR, Ali MK, Rolka D, Williams DE, Geiss L. Changes in diabetes-related complications in the United States, 1990-2010. N Engl J Med. 2014 Apr 17;370(16):1514-23. doi: 10.1056/NEJMoa1310799.
PubMed 24738668American Diabetes Association. 4. Prevention or Delay of Type 2 Diabetes. Diabetes Care. 2016 Jan;39 Suppl 1:S36-8. doi: 10.2337/dc16-S007. No abstract available.
PubMed 26696678Alouki K, Delisle H, Bermudez-Tamayo C, Johri M. Lifestyle Interventions to Prevent Type 2 Diabetes: A Systematic Review of Economic Evaluation Studies. J Diabetes Res. 2016;2016:2159890. doi: 10.1155/2016/2159890. Epub 2016 Jan 13.
PubMed 26885527Aziz Z, Absetz P, Oldroyd J, Pronk NP, Oldenburg B. A systematic review of real-world diabetes prevention programs: learnings from the last 15 years. Implement Sci. 2015 Dec 15;10:172. doi: 10.1186/s13012-015-0354-6.
PubMed 26670418Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6):393-403. doi: 10.1056/NEJMoa012512.
PubMed 11832527Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M; Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001 May 3;344(18):1343-50. doi: 10.1056/NEJM200105033441801.
PubMed 11333990Li G, Zhang P, Wang J, Gregg EW, Yang W, Gong Q, Li H, Li H, Jiang Y, An Y, Shuai Y, Zhang B, Zhang J, Thompson TJ, Gerzoff RB, Roglic G, Hu Y, Bennett PH. The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study. Lancet. 2008 May 24;371(9626):1783-9. doi: 10.1016/S0140-6736(08)60766-7.
PubMed 18502303DeFronzo RA, Tripathy D, Schwenke DC, Banerji M, Bray GA, Buchanan TA, Clement SC, Henry RR, Hodis HN, Kitabchi AE, Mack WJ, Mudaliar S, Ratner RE, Williams K, Stentz FB, Musi N, Reaven PD; ACT NOW Study. Pioglitazone for diabetes prevention in impaired glucose tolerance. N Engl J Med. 2011 Mar 24;364(12):1104-15. doi: 10.1056/NEJMoa1010949.
PubMed 21428766Carlsson LM, Peltonen M, Ahlin S, Anveden A, Bouchard C, Carlsson B, Jacobson P, Lonroth H, Maglio C, Naslund I, Pirazzi C, Romeo S, Sjoholm K, Sjostrom E, Wedel H, Svensson PA, Sjostrom L. Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects. N Engl J Med. 2012 Aug 23;367(8):695-704. doi: 10.1056/NEJMoa1112082.
PubMed 22913680Schauer PR, Mingrone G, Ikramuddin S, Wolfe B. Clinical Outcomes of Metabolic Surgery: Efficacy of Glycemic Control, Weight Loss, and Remission of Diabetes. Diabetes Care. 2016 Jun;39(6):902-11. doi: 10.2337/dc16-0382.
PubMed 27222548Lim EL, Hollingsworth KG, Aribisala BS, Chen MJ, Mathers JC, Taylor R. Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia. 2011 Oct;54(10):2506-14. doi: 10.1007/s00125-011-2204-7. Epub 2011 Jun 9.
PubMed 21656330Sattar N. Revisiting the links between glycaemia, diabetes and cardiovascular disease. Diabetologia. 2013 Apr;56(4):686-95. doi: 10.1007/s00125-012-2817-5. Epub 2013 Jan 27.
PubMed 23354123Buse JB, Caprio S, Cefalu WT, Ceriello A, Del Prato S, Inzucchi SE, McLaughlin S, Phillips GL 2nd, Robertson RP, Rubino F, Kahn R, Kirkman MS. How do we define cure of diabetes? Diabetes Care. 2009 Nov;32(11):2133-5. doi: 10.2337/dc09-9036. No abstract available.
PubMed 19875608Weng J, Li Y, Xu W, Shi L, Zhang Q, Zhu D, Hu Y, Zhou Z, Yan X, Tian H, Ran X, Luo Z, Xian J, Yan L, Li F, Zeng L, Chen Y, Yang L, Yan S, Liu J, Li M, Fu Z, Cheng H. Effect of intensive insulin therapy on beta-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomised parallel-group trial. Lancet. 2008 May 24;371(9626):1753-60. doi: 10.1016/S0140-6736(08)60762-X.
PubMed 18502299Sosnowski C, Janeczko-Sosnowska E. [Commentary to the article: Kahn SE, Haffner SM, Heise MA, et al. ADOPT Study Group. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006; 355: 2427-43]. Kardiol Pol. 2007 Feb;65(2):214-6; discussion 216-7. No abstract available. Polish.
PubMed 17366371
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized, Parallel-group, Adaptive Design Phase IIb/III, Multicenter Study, to Assess the Efficacy of Polychemotherapy for Inducing Remission of Newly Diagnosed Type 2 Diabetes.
- ClinicalTrials.gov ID
- NCT04271189
- Acronym / sponsor ID
- MIRACLE / 2018-833-12
- Conditions
- Newly Diagnosed Type 2 Diabetes
- Keywords
- Type 2 diabetes, Polychemotherapy, Diabetes remission
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 108 participants (actual)
- Lead sponsor
- Azienda Ospedaliero-Universitaria di ParmaUniversity, hospital or other
- Study start
- 1 Sep 2020 (actual)
- Primary completion
- 31 Aug 2024 (actual)
- Study completion
- 31 Dec 2024 (actual)
- First posted
- 17 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Hypothesis: at diagnosis of T2DM, a 4 month course of oral polychemotherapy (POLYCHEM), by engaging multiple glucose lowering mechanisms, results into euglycemia and, after suspension, in T2DM remission in a clinically significant higher number of patients when compared to standard diabetes care (SDC).
- Diabetes remission: simultaneous nondiabetic values of fasting glucose, 2-hour glucose (after OGTT) and HbA1c for at least 12 months with no pharmacologic/surgical treatment of diabetes.
- Complete remission: all values of fasting glucose, 2-hour glucose and HbA1c are within the limits of normal glucose regulation; otherwise, remission is partial.
- Hyperglycemia remission as in diabetes remission, but duration<12 months.
Based on the "Consensus Report: Definition and Interpretation of Remission in Type 2 Diabetes" published on Diabetes Care 2021;44(10):2438-2444, remission should be defined as a return of HbA1c to <6.5% (<48 mmol/mol) that occurs spontaneously or following an intervention and that persists for at least 3 months in the absence of usual glucose-lowering pharmacotherapy.
A POLYCHEM (metformin, pioglitazone, sitagliptin and empagliflozin) will be used to improve:
- Insulin sensitivity of endogenous glucose output (EGO) and peripheral (muscle) glucose uptake (PGU);
- Beta cell function;
- GLP-1 and GIP bioavailability. To these effects, the direct glycosuric action of EMPA is added; EMPA effects on alpha cell and liver (increased glucagon secretion and EGO), may be, at least in part, counterbalanced by SITA and MET/PIO, respectively. Increased heart failure events with PIO may be, at least in part, counteracted by EMPA.
In many patients POLYCHEM should result in stable euglycemia, with negligible risk of hypoglycemia, and the number of patients in T2DM remission should be much higher than with MET+SU. The underpinning is that euglycemia reverses the detrimental effects of glucose toxicity and glucose regulation can be maintained in the nondiabetic range.
If the invesigators hypothesis is proved, POLYCHEM would be a convenient, simple and relatively unexpensive strategy to induce remission in a great number of patients with newly diagnosed T2DM. Novel, more efficacious goals of therapy could be introduced. Duration of remission is expected to delay the processes which result into the T2DM related risk of tissue damage. At the patient acceptance level, the trade off between the full T2DM burden (diabetes, its care and the risk of its complications) and the risk of T2DM relapse should favor the latter. At the society level, achieving a durable remission in a substantial number of these patients should attenuate, or even annull, the rises in prevalence, burden and tolls of "active" T2DM.
Patients with newly diagnosed (i.e. less than 6 months) T2DM will be recruited in the Diabetes Outpatient Clinics and will provide informed written consent before participation. After a screening visit (V0), patients will be randomized 1:1, with center stratification through web-based data collection (eCRF), to receive POLYCHEM or SDC with standard lifestyle intervention in both.
In both arms, patients will undergo planned visits at week 0 (V1), week 16 (V2), and week 28 (V3), after at least 3 days of drug washout. Patients will perform weekly a 6-point home blood glucose profile. Between week 17 and week 28, if a patient in hyperglycemia remission relapses, V3 will be anticipated (V3B), after which the patient will be treated as in SDC and will be re-evaluated at week 28 .
Visit procedures:
- V0: assessment of patient eligibility , including medical history, physical examination, and lab exams, if needed.
- V0S: between V0 and V1; signature of informed written consent and randomization.
- V1, V2, V3 and V3B: assessment of anthropometry, ambulatory blood pressure and heart rate, WBC, fasting glucose, HbA1c, lipids, AST, ALT, creatinine, lipase, urine analysis, microalbuminuria, insulin, C-peptide, glucagon, GLP-1, GIP, quality of life (QoL), and, only in V1, blood for DNA collection (the last for post hoc studies).
POLYCHEM-ARM: After V1, patients will start POLYCHEM (MET titrated to 1000 mg b.i.d., PIO 15 mg b.i.d., SITA 100 mg q.d., EMPA 10 mg q.d.) for 16 weeks, at the end of which (V2) patients in hyperglycemia remission stop drug therapy, the others are transferred to SDC. Patients with MET intolerance will be treated with PIO+SITA+EMPA only.
SDC-ARM: After V1, patients will continue their SDC for 16 weeks, at the end of which (V2) patients in hyperglycemia remission stop drug therapy, the others continue SDC.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Multicenter, open label pragmatic phase IIb/III RCT with a duration of 3 years
| Arm | Type | Receives |
|---|---|---|
| POLYCHEM | Experimental | Drug: Metformin-Sitagliptin-Empaglifozin-PioglitazoneMetformin (extended release), Pioglitazone, Sitagliptin and Empaglifozin. |
| STANDARD CARE | Active comparator | Drug: Standard of careStandard of care according to the local health service. |
Who may qualify
- Ages
- 35 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (9 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metformin-Sitagliptin-Empaglifozin-PioglitazoneAlso: POLYCHEM1000 mg metformin (extended release) b.i.d., pioglitazone 15 mg b.i.d., sitagliptin 100 mg q.d., empaglifozin 10 mg q.d.. | Drug | POLYCHEM |
| Standard of careAlso: SDCUsual medical care to treat diabetes. | Drug | STANDARD CARE |
Primary outcome
Assess the T2DM remission rate in patients with newly diagnosed T2DM treated with either POLYCHEM or with SDC for 16 weeks.
Time frame: 12 weeks after the end of treatment
Remission was defined as HbA1c <6.5% or 48mmol/mol for at least 12 weeks without pharmacologic or surgical treatment for diabetes.
9 secondary outcomes
Assess the proportion of complete T2DM remission rate in the 2 groups
Time frame: 12 weeks after the end of treatment
Monitor the quality of life EQ-5D-DL
Time frame: 0, 16, 28 weeks
Monitor the quality of life ADDQOL
Time frame: 0, 16, 28 weeks
Monitor the costs of National Health System service utilization
Time frame: 0, 16, 28 weeks
Quantify the effects of either POLYCHEM or SDC on the main determinants of glucose regulation
Time frame: 0, 16, 28 weeks
Quantify the effects of either POLYCHEM or SDC on the main determinants of glucose regulation
Time frame: 0, 16, 28 weeks
Quantify the effects of either POLYCHEM or SDC on the main determinants of glucose regulation
Time frame: 0, 16, 28 weeks
Quantify the effects of either POLYCHEM or SDC on the main determinants of glucose regulation
Time frame: 0, 16, 28 weeks
Quantify the effects of either POLYCHEM or SDC on the main determinants of glucose regulation
Time frame: 0, 16, 28 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2025.
- Background: PubMed 24738668Gregg EW, Li Y, Wang J, Burrows NR, Ali MK, Rolka D, Williams DE, Geiss L. Changes in diabetes-related complications in the United States, 1990-2010. N Engl J Med. 2014 Apr 17;370(16):1514-23. doi: 10.1056/NEJMoa1310799.
- Background: PubMed 26696678American Diabetes Association. 4. Prevention or Delay of Type 2 Diabetes. Diabetes Care. 2016 Jan;39 Suppl 1:S36-8. doi: 10.2337/dc16-S007. No abstract available.
- Background: PubMed 26885527Alouki K, Delisle H, Bermudez-Tamayo C, Johri M. Lifestyle Interventions to Prevent Type 2 Diabetes: A Systematic Review of Economic Evaluation Studies. J Diabetes Res. 2016;2016:2159890. doi: 10.1155/2016/2159890. Epub 2016 Jan 13.
- Background: PubMed 26670418Aziz Z, Absetz P, Oldroyd J, Pronk NP, Oldenburg B. A systematic review of real-world diabetes prevention programs: learnings from the last 15 years. Implement Sci. 2015 Dec 15;10:172. doi: 10.1186/s13012-015-0354-6.
- Background: PubMed 11832527Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6):393-403. doi: 10.1056/NEJMoa012512.
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- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Riccardo Bonadonna, MD principal investigator
Azienda Ospedaliero-Universitaria di Parma
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Metformin-Sitagliptin-Empaglifozin-Pioglitazone in people with Newly Diagnosed Type 2 Diabetes, run by Azienda Ospedaliero-Universitaria di Parma at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assess the T2DM remission rate in patients with newly diagnosed T2DM treated with either POLYCHEM or with SDC for 16 weeks. (time frame: 12 weeks after the end of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04271189, which also lists 32 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2025.