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Diabetes Mellitus, Type IIPhase 3NCT02946632

Effectiveness & Tolerability of Novel, Initial Triple Combination Therapy vs Conventional Therapy in Type 2 Diabetes

A Phase 3 study testing triple combination therapy and Stepwise add-on therapy in people with Diabetes Mellitus, Type II, run by Korea University Anam Hospital at 1 site in South Korea.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

In this study, the investigators will assess the efficacy and tolerability of a novel, initial triple combination therapy with metformin, saxaglipitin, and dapagliflozin, compared to conventional stepwise add-on therapy in drug-naïve patients with recently onset type 2 diabetes. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Diabetes Mellitus, Type II
What is being tested?
triple combination therapy and Stepwise add-on therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
104 participants
Where
1 siteSouth Korea
Study dates
Dec 2016to Dec 2019
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 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Drug-naïve patients with type 2 diabetes by American Diabetes Association criteria
  • HbA1c ≥ 8%, < 10.5% at screening
  • Age ≥ 18 years, < 65 years
  • Body mass index (BMI) ≥ 23 kg/m2, < 35 kg/m2
  • Estimated GFR (eGFR) ≥ 60 ml/min/1.73m2

Who cannot join

  • Uncontrolled hyperglycemia > 270 mg/dl after an overnight fast
  • Diabetic ketoacidosis
  • Type 1 diabetes
  • Confirmed cardiovascular disease (acute coronary syndrome, stroke, or transient ischemic attack) within 3 months of screening
  • Congestive heart failure (New York Heart Association functional class IV)
  • severe hepatic dysfunction (serum levels of either AST, ALT, or alkaline phosphatase above 3 x upper limit of normal (ULN))
Show all 9Show fewer
  • alcohol abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake
  • pregnant women, women with potential of pregnancy not using adequate contraception method as evaluated by the investigator, lactating women
  • use of systemic glucocorticoid

Trial locations and contacts

1 site in 1 country.

SinGon Kim, MD contact

010-4191-0958

k50367@korea.ac.kr

South Korea1 site

  • Korea University Anam Hospital

    Seoul

Other trials in South Korea

About this study

Official title: Effectiveness and Tolerability of Novel, Initial Triple Combination Therapy With Xigduo (Dapagliflozin Plus Metformin) and Saxagliptin vs. Conventional Stepwise add-on Therapy in Drug-naïve Patients With Type 2 Diabetes

In this study, the investigators will assess the efficacy and tolerability of a novel, initial triple combination therapy with metformin, saxaglipitin, and dapagliflozin, compared to conventional stepwise add-on therapy in drug-naïve patients with recently onset type 2 diabetes.

Read the detailed description

ADA/EASD guideline recommends sequential treatment approach starting with metformin, and adding other classes of anti-diabetic medications if target HbA1c is not achieved. However, several clinical studies clearly showed that initial dual or triple combination therapy was more favorable in terms of glycemic control.

A DPP-4 inhibitor saxagliptin increases serum level of GLP-1, and potentiates its action of increasing glucose-dependent insulin secretion and lowering glucagon secretion. A SGLT-2 inhibitor dapagliflozin lowers hyperglycemia via blocking SGLT-2 to increase glucosuria, that is, in an insulin-independent manner. Therefore, the mechanism of action of these drugs are complimentary to that of metformin, and all of these have a low risk of hypoglycemia and weight gain.

Being tested
triple combination therapy, Stepwise add-on therapy
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.

  • triple combination therapyDrug

    Also called metformin 1000mg, dapagliflozin 10mg, saxagliptin 5mg

    Xigduo (metformin 1000mg + dapagliflozin 10mg) saxagliptin 5mg

  • Stepwise add-on therapyDrug

    Also called Metformin, Glimepiride, Sitagliptin

    metformin -> glimepirde -> sitagliptin

Study groups in NCT02946632
Study groupRoleWhat they receive
Triple combination therapy groupExperimentalXigduo (metformin 1000mg + dapagliflozin 10mg), saxagliptin 5mg once daily for 104 weeks
Receives: Drug: triple combination therapy
Stepwise add-on therapy groupActive comparator* Participants were started on metformin 1000mg once daily after screening \& assignment * At each visits, FPG and HbA1c are measured. Sequential add-on therapy regimen is described
Receives: Drug: Stepwise add-on therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of patients who met HbA1c < 6.5% without hypoglycaemia, weight gain, or discontinuation due to adverse events at 104 weeks

    Measured: 104 weeks

Secondary outcomes (6)

  1. ∙ Proportion of patients who met HbA1c < 6.5% without hypoglycaemia, weight gain, or discontinuation due to adverse events at 52 weeks

    Measured: 52 weeks

  2. Proportion of patients who met HbA1c < 7.0% without hypoglycaemia, weight gain, or discontinuation due to adverse events at 104 weeks

    Measured: 104 weeks

  3. Change in body HbA1c from baseline to week 104

    Measured: 104 weeks

  4. Change in body weight from baseline to week 104

    Measured: 104 weeks

  5. Change in systolic blood pressure from baseline to week 104

    Measured: 104 weeks

  6. Changes in fat and lean mass from baseline to at 104 weeks

    Measured: 104 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Oct 2016 (estimated)
  2. Study startDec 2016
  3. Primary completionDec 2019 (estimated)
  4. Study completionDec 2019 (estimated)

Resources

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
Masking
None (open label)
Enrolment
104 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02946632
Sponsor's protocol ID
TRIPLE-AXEL-ESR
Status last verified
Oct 2016
First submitted
25 Oct 2016
Last updated
27 Oct 2016
Results posted
No
Data monitoring committee
Yes

Publications

  • Klein R, Klein BE, Moss SE. Relation of glycemic control to diabetic microvascular complications in diabetes mellitus. Ann Intern Med. 1996 Jan 1;124(1 Pt 2):90-6. doi: 10.7326/0003-4819-124-1_part_2-199601011-00003.

    PubMed 8554220

  • Moss SE, Klein R, Klein BE, Meuer SM. The association of glycemia and cause-specific mortality in a diabetic population. Arch Intern Med. 1994 Nov 14;154(21):2473-9.

    PubMed 7979844

  • 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.

    PubMed 9742976

  • Action to Control Cardiovascular Risk in Diabetes Study Group; Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr, Probstfield JL, Simons-Morton DG, Friedewald WT. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008 Jun 12;358(24):2545-59. doi: 10.1056/NEJMoa0802743. Epub 2008 Jun 6.

    PubMed 18539917

  • ADVANCE Collaborative Group; Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P, Grobbee D, Hamet P, Harrap S, Heller S, Liu L, Mancia G, Mogensen CE, Pan C, Poulter N, Rodgers A, Williams B, Bompoint S, de Galan BE, Joshi R, Travert F. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008 Jun 12;358(24):2560-72. doi: 10.1056/NEJMoa0802987. Epub 2008 Jun 6.

    PubMed 18539916

  • Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008 Oct 9;359(15):1577-89. doi: 10.1056/NEJMoa0806470. Epub 2008 Sep 10.

    PubMed 18784090

  • Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR; American Diabetes Association (ADA); European Association for the Study of Diabetes (EASD). Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012 Jun;35(6):1364-79. doi: 10.2337/dc12-0413. Epub 2012 Apr 19. No abstract available.

    PubMed 22517736

  • Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT, Bush MA, Dagogo-Jack S, Davidson MB, Einhorn D, Garvey WT, Grunberger G, Handelsman Y, Hirsch IB, Jellinger PS, McGill JB, Mechanick JI, Rosenblit PD, Umpierrez GE, Davidson MH. American Association of Clinical Endocrinologists' comprehensive diabetes management algorithm 2013 consensus statement--executive summary. Endocr Pract. 2013 May-Jun;19(3):536-57. doi: 10.4158/EP13176.CS. No abstract available.

    PubMed 23816937

  • Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009 Apr;58(4):773-95. doi: 10.2337/db09-9028. No abstract available.

    PubMed 19336687

  • Abdul-Ghani MA, Puckett C, Triplitt C, Maggs D, Adams J, Cersosimo E, DeFronzo RA. Initial combination therapy with metformin, pioglitazone and exenatide is more effective than sequential add-on therapy in subjects with new-onset diabetes. Results from the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT): a randomized trial. Diabetes Obes Metab. 2015 Mar;17(3):268-75. doi: 10.1111/dom.12417. Epub 2015 Jan 7.

    PubMed 25425451

  • Lewin A, DeFronzo RA, Patel S, Liu D, Kaste R, Woerle HJ, Broedl UC. Initial combination of empagliflozin and linagliptin in subjects with type 2 diabetes. Diabetes Care. 2015 Mar;38(3):394-402. doi: 10.2337/dc14-2365. Epub 2015 Jan 29.

    PubMed 25633662

  • Rosenstock J, Hansen L, Zee P, Li Y, Cook W, Hirshberg B, Iqbal N. Dual add-on therapy in type 2 diabetes poorly controlled with metformin monotherapy: a randomized double-blind trial of saxagliptin plus dapagliflozin addition versus single addition of saxagliptin or dapagliflozin to metformin. Diabetes Care. 2015 Mar;38(3):376-83. doi: 10.2337/dc14-1142. Epub 2014 Oct 28.

    PubMed 25352655

  • Augeri DJ, Robl JA, Betebenner DA, Magnin DR, Khanna A, Robertson JG, Wang A, Simpkins LM, Taunk P, Huang Q, Han SP, Abboa-Offei B, Cap M, Xin L, Tao L, Tozzo E, Welzel GE, Egan DM, Marcinkeviciene J, Chang SY, Biller SA, Kirby MS, Parker RA, Hamann LG. Discovery and preclinical profile of Saxagliptin (BMS-477118): a highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J Med Chem. 2005 Jul 28;48(15):5025-37. doi: 10.1021/jm050261p.

    PubMed 16033281

  • List JF, Woo V, Morales E, Tang W, Fiedorek FT. Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care. 2009 Apr;32(4):650-7. doi: 10.2337/dc08-1863. Epub 2008 Dec 29.

    PubMed 19114612

  • Park IR, Moon JS, Ha J, Ko E, Lee YH, Cho HC, Kwak SH, Lim S, Moon MK, Kim DL, Kim TH, Kim SG, Kim NH. beta-Cell Recovery Patterns With Initial Combination Versus Stepwise Therapy in Newly Diagnosed Type 2 Diabetes: TRIPLE-AXEL Post Hoc Analysis. Diabetes Obes Metab. 2026 Nov 3. doi: 10.1111/dom.71516. Online ahead of print.

    PubMed 42977550

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing triple combination therapy and Stepwise add-on therapy in people with Diabetes Mellitus, Type II, run by Korea University Anam Hospital at 1 site in South Korea.

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 5 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: status not confirmed, as of the sponsor's last update on 27 Oct 2016. 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 South Korea. 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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact SinGon Kim, MD (010-4191-0958, k50367@korea.ac.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of patients who met HbA1c < 6.5% without hypoglycaemia, weight gain, or discontinuation due to adverse events at 104 weeks (time frame: 104 weeks). 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 NCT02946632, which also lists 17 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 27 Oct 2016.

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