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ObesityPhase 3NCT03419624

The Potential of Dapagliflozin Plus Exenatide in Obese Insulin-resistant Patients

A Phase 3 study testing Dapagliflozin 10mg, Exenatide 2 mg [Bydureon] and Insulin in people with Obesity and Diabetes Mellitus, Type 2, run by Universitätsklinikum Hamburg-Eppendorf at 4 sites in Germany.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a 28-week, multi-center, randomized, double-blind, placebo-controlled trial to study a potential synergistic effect of Dapagliflozin plus Exenatide once-weekly in combination with high-dose intensive insulin therapy compared to Placebo in obese insulin-resistant patients with Type 2 Diabetes mellitus (T2DM)… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Obesity, Diabetes Mellitus, Type 2
What is being tested?
Dapagliflozin 10mg, Exenatide 2 mg [Bydureon] and Insulin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
13 participants
Where
4 sitesGermany
Study dates
19 Feb 2018to 5 Aug 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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

None listed.

Who cannot join

  • Diagnosis of Type 1 Diabetes
  • History of diabetic ketoacidosis, hyperosmolar coma or corticosteroid-induced Type 2 diabetes
  • Patients with significant thyroid disease
  • Patients with history of acute or chronic pancreatitis
  • Clinically significant cardiovascular disease or procedure within 3 months prior to enrolment or expected to require coronary revascularization procedure
  • Presence of history of severe congestive heart failure (NYHA III and IV)
Show all 33Show fewer
  • Creatinin-Clearance of < 60 ml/min based on local laboratory results
  • Concomitant medication with loop diuretics
  • Patients who, as judged by the investigator, may be at risk for dehydration or volume depletion that may affect the patient's safety (including e.g. patients with a history of Diabetes insipidus)
  • Pregnant women
  • Administration of any other antidiabetic therapy, other than insulin (see inclusion criterion no.4 and 5) and metformin with a stable total daily dose ≥ 1500 mg or the maximum tolerated dose of metformin within 3 months prior to enrolment
  • History of, or currently have, acute or chronic pancreatitis, or have triglyceride concentrations ≥ 700 mg/dL (≥ 7.98 mmol/L) at Visit 0 (Screening).
  • History or presence of inflammatory bowel disease or other severe GI diseases, particularly those which may impact gastric emptying, such as gastroparesis or pyloric stenosis.
  • History of gastric bypass surgery or gastric banding surgery, or either procedure is planned during the time period of the study. Current use of gastric balloons is also excluded.
  • Significant hepatic disease, including, but not limited to, acute hepatitis, chronic active hepatitis, or severe hepatic insufficiency, including patients with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or total bilirubin (TB) >2 mg/dL (>34.2 μmol/L) (patients with TB >2 mg/dL [>34.2 μmol/L] and documented Gilbert's syndrome will be allowed to participate).
  • Known history of hepatotoxicity with any medication
  • Known history of severe hepatobiliary disease.
  • Positive serological test for hepatitis B or hepatitis C.
  • Known or suspected human immunodeficiency virus (HIV) infection.
  • History of organ transplantation.
  • Presence or history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN 2) OR a family history of medullary thyroid carcinoma or MEN 2.
  • Malignancy (with the exception of basal and squamous cell carcinoma of the skin) within 5 years of Visit 0 (Screening).
  • Hemoglobinopathy, hemolytic anemia, or chronic anemia (haemoglobin concentration <11.5 g/dL [115 g/L] for males, <10.5 g/dL [105 g/L] for females) or any other condition known to interfere with the HbA1c methodology.
  • Patients with abnormal test results of hematocrit (hematocrit > 50% for men; hematocrit > 47% for women)
  • Has donated blood or had a significant blood loss within 2 months of first dose of study medication or is planning to donate blood during the study.
  • Has donated plasma within 7 days prior to first dose of study medication.
  • Any exposure to Exenatide (including BYETTA®, BYDUREON, or exenatide suspension).
  • Any exposure to Dapagliflozin or any SGLT-2 inhibitor.
  • Has been treated, is currently being treated, or is expected to require or undergo treatment with any of the following treatment excluded medications:
  • Any DPP-4 inhibitor within 3 months prior to Visit 0 (Screening).
  • Any GLP-1 analog within 1 year prior to Visit 0 (Screening).
  • Systemic corticosteroids within 3 months prior to Visit 0 (Screening) by oral, intravenous, intra-articular, or intramuscular route; or potent, inhaled, or intrapulmonary (including ADVAIR) steroids known to have a high rate of systemic absorption. For examples of excluded steroids, refer to Section 7.7.
  • Prescription or over-the-counter weight loss medications within 3 months prior to Visit 0 (Screening).

Trial locations and contacts

4 sites in 1 country.

Germany4 sites

  • University Medical Center Hamburg-Eppendorf

    Hamburg, 20246

  • Diabetologische Schwerpunktpraxis Harburg

    Hamburg, 21073

  • Gemeinschaftspraxis für Innere Medizin und Diabetologie

    Hamburg, 22607

  • Diabeteszentrum Oldenburg

    Oldenburg, Lower Saxony, 23758

Other trials in Germany

About this study

Official title: A 28-week, Multi-center Randomized, Double-blind, Placebo-controlled Study to Evaluate the Potential of Dapagliflozin Plus Exenatide in Combination With High-dose Intensive Insulin Therapy Compared to Placebo in Obese Insulin-resistant Patients With Type 2 Diabetes Mellitus (Proof-of-concept Study)

This is a 28-week, multi-center, randomized, double-blind, placebo-controlled trial to study a potential synergistic effect of Dapagliflozin plus Exenatide once-weekly in combination with high-dose intensive insulin therapy compared to Placebo in obese insulin-resistant patients with Type 2 Diabetes mellitus (T2DM) and inadequate glycemic control (HbA1c≥8.0% and ≤ 11.0%).

Read the detailed description

In this proof-of-concept study the potential of treatment with Dapagliflozin plus Exenatide added to high-dose intensive insulin therapy compared to Placebo added to high-dose intensive insulin with active insulin up-titration for change in HbA1c from baseline to week 28 shall be explored and generate initial data on the primary outcome. We hypothesize that SGLT-2 inhibition and GLP-1 receptor agonism may be a rational combination therapy that addresses a broad range of pathophysiological defects associated with T2DM in obesity and may reduce HbA1c levels in patients with severe insulin resistance. In a third treatment arm, patients will be treated with Exenatide monotherapy added to high-dose intensive Insulin therapy to study additive effects of Dapagliflozin and Exenatide.

Being tested
Dapagliflozin 10mg, Exenatide 2 mg [Bydureon], Placebo Oral Tablet, Placebo injection, Insulin
Keywords
Dapagliflozin, Exenatide, high-dose insulin therapy, SGLT-2 inhibitor, GLP-1 receptor agonist
Medical subject headings
Obesity, Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dapagliflozin 10mgDrug

    Dapagliflozin 10 mg tablet once daily

  • Exenatide 2 mg [Bydureon]Drug

    Exenatide 2 mg injection once weekly

  • Placebo Oral TabletDrug

    Placebo oral tablet once daily

  • Placebo injectionDrug

    Placebo injection once weekly

  • InsulinDrug

    daily Insulin injections

  • Metformin, if taken beforeDrug

    If the Patient has taken Metformin prior to enrollment, he or she will continue to take it.

Study groups in NCT03419624
Study groupRoleWhat they receive
Dapagliflozin plus ExenatideExperimentalDapagliflozin (10mg orally once daily) plus Exenatide (2mg subcutaneous once-weekly injection) as add-on to high-dose intensive insulin therapy
Receives: Drug: Dapagliflozin 10mg; Drug: Exenatide 2 mg [Bydureon]; Drug: Insulin; Drug: Metformin, if taken before
Placebo plus PlaceboPlacebo comparatorPlacebo (film-coated tablet once daily) plus Placebo (subcutaneous once-weekly injection) as add-on to high-dose intensive insulin therapy
Receives: Drug: Placebo Oral Tablet; Drug: Placebo injection; Drug: Insulin; Drug: Metformin, if taken before
Placebo plus ExenatideActive comparatorPlacebo (film-coated tablet once daily) plus Exenatide (2mg subcutaneous once- weekly injection) as add-on to high dose intensive insulin therapy
Receives: Drug: Exenatide 2 mg [Bydureon]; Drug: Placebo Oral Tablet; Drug: Insulin; Drug: Metformin, if taken before

What is being measured

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

  1. Change in HbA1c from baseline (week 0) to week 28

    To compare the absolute change from baseline in HbA1c at week 28 between Dapagliflozin plus Exenatide, Placebo or Exenatide monotherapy added to high-dose intensive insulin therapy

    Measured: 28 weeks

Secondary outcomes (6)

  1. Change in HbA1c from baseline (week 0) to week 14

    To compare the absolute change in HbA1c from baseline at week 0 to week 14 between Dapagliflozin plus Exenatide, Placebo or Exenatide monotherapy added to high-dose intensive insulin therapy

    Measured: 14 weeks

  2. Change in total body weight from baseline (week 0) to week 14 and 28

    To compare the change in total body weight from baseline at week 0 to week 14 and 28 between Dapagliflozin plus Exenatide, Placebo or Exenatide monotherapy added to high-dose intensive insulin therapy

    Measured: 28 weeks

  3. Change in BMI from baseline (week 0) to week 14 and 28

    To compare the change in BMI from baseline at week 0 to week 14 and 28 between Dapagliflozin plus Exenatide, Placebo or Exenatide monotherapy added to high-dose intensive insulin therapy

    Measured: 28 weeks

  4. Change in FPG from baseline (week 0) to week 14 and 28

    To compare the change in fasting plasma glucose (FPG) from baseline at week 0 to week 14 and 28 between Dapagliflozin plus Exenatide, Placebo or Exenatide monotherapy added to high-dose intensive insulin therapy

    Measured: 28 weeks

  5. Change in TDID from baseline (week 0) to week 14 and 28

    To compare the change in total daily insulin dose (TDID) from baseline at week 0 to week 14 and 28 between Dapagliflozin plus Exenatide, Placebo or Exenatide monotherapy added to high-dose intensive insulin therapy

    Measured: 28 weeks

  6. Proportion of patients achieving HbA1c of ≤ 7% at week 28 compared to baseline

    To compare the number of patients achieving HbA1c of ≤ 7% at week 28 compared to baseline at week 0 between Dapagliflozin plus Exenatide, Placebo or Exenatide monotherapy added to high-dose intensive insulin therapy

    Measured: 28 weeks

Timeline

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

  1. First posted5 Feb 2018
  2. Study start19 Feb 2018
  3. Primary completion1 Apr 2019
  4. Study completion5 Aug 2019

Why it stopped: Delay in patient enrolment

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
Double blind
Who is masked
Participant, Investigator
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03419624
Sponsor's protocol ID
UKE-DapEx-001
Status last verified
Mar 2020
First submitted
17 Jan 2018
Last updated
31 Mar 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Prasad-Reddy L, Isaacs D. A clinical review of GLP-1 receptor agonists: efficacy and safety in diabetes and beyond. Drugs Context. 2015 Jul 9;4:212283. doi: 10.7573/dic.212283. eCollection 2015.

    PubMed 26213556

  • Wilding JP, Woo V, Soler NG, Pahor A, Sugg J, Rohwedder K, Parikh S; Dapagliflozin 006 Study Group. Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin: a randomized trial. Ann Intern Med. 2012 Mar 20;156(6):405-15. doi: 10.7326/0003-4819-156-6-201203200-00003.

    PubMed 22431673

  • Finkelstein EA, Khavjou OA, Thompson H, Trogdon JG, Pan L, Sherry B, Dietz W. Obesity and severe obesity forecasts through 2030. Am J Prev Med. 2012 Jun;42(6):563-70. doi: 10.1016/j.amepre.2011.10.026.

    PubMed 22608371

  • 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

  • Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR. Management of hyperglycaemia 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). Diabetologia. 2012 Jun;55(6):1577-96. doi: 10.1007/s00125-012-2534-0. Epub 2012 Apr 20. No abstract available.

    PubMed 22526604

  • Tatarkiewicz K, Polizzi C, Villescaz C, D'Souza LJ, Wang Y, Janssen S, Parkes DG. Combined antidiabetic benefits of exenatide and dapagliflozin in diabetic mice. Diabetes Obes Metab. 2014 Apr;16(4):376-80. doi: 10.1111/dom.12237. Epub 2013 Dec 9.

    PubMed 24251534

  • Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: update regarding thiazolidinediones: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2008 Jan;31(1):173-5. doi: 10.2337/dc08-9016. No abstract available.

    PubMed 18165348

  • Wangnoo SK, Sethi B, Sahay RK, John M, Ghosal S, Sharma SK. Treat-to-target trials in diabetes. Indian J Endocrinol Metab. 2014 Mar;18(2):166-74. doi: 10.4103/2230-8210.129106.

    PubMed 24741511

  • Holman R. Metformin as first choice in oral diabetes treatment: the UKPDS experience. Journ Annu Diabetol Hotel Dieu. 2007:13-20.

    PubMed 18613325

  • Blevins T, Pullman J, Malloy J, Yan P, Taylor K, Schulteis C, Trautmann M, Porter L. DURATION-5: exenatide once weekly resulted in greater improvements in glycemic control compared with exenatide twice daily in patients with type 2 diabetes. J Clin Endocrinol Metab. 2011 May;96(5):1301-10. doi: 10.1210/jc.2010-2081. Epub 2011 Feb 9.

    PubMed 21307137

  • Diamant M, Van Gaal L, Stranks S, Northrup J, Cao D, Taylor K, Trautmann M. Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial. Lancet. 2010 Jun 26;375(9733):2234-43. doi: 10.1016/S0140-6736(10)60406-0.

    PubMed 20609969

  • Sharma S, Jain S. Prevalence of Obesity among Type-2 Diabetics. J Hum Ecol 2009;25:31-5.

  • Dixon JB, O'Brien PE. Health outcomes of severely obese type 2 diabetic subjects 1 year after laparoscopic adjustable gastric banding. Diabetes Care. 2002 Feb;25(2):358-63. doi: 10.2337/diacare.25.2.358.

    PubMed 11815510

  • 2012. Guideline on clinical investigation of medicinal products in the treatment or prevention of diabetes mellitus n.d. ema.europa.eu.

  • Anderson SL. Dapagliflozin efficacy and safety: a perspective review. Ther Adv Drug Saf. 2014 Dec;5(6):242-54. doi: 10.1177/2042098614551938.

    PubMed 25436106

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Dapagliflozin 10mg, Exenatide 2 mg [Bydureon] and Insulin in people with Obesity and Diabetes Mellitus, Type 2, run by Universitätsklinikum Hamburg-Eppendorf at 4 sites in Germany.

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 0 inclusion and 33 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: stopped early, as of the sponsor's last update on 31 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Germany. 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. Some participants in this study may receive a placebo. 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 was stopped early (reason given: Delay in patient enrolment). Results are not available in the source record.

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?

Change in HbA1c from baseline (week 0) to week 28 (time frame: 28 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 NCT03419624, which also lists 19 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 31 Mar 2020.

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