Empagliflozin in Post-Transplantation Diabetes Mellitus

NCT03113110 | Completed Phase 2

• 2 other identifiers: EUDRACT-Nr: 2016-001580-37EK-No. 1366/2016
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

RELEVANCE: Up to 50% of patients without previously known disorders of glucose metabolism develop posttransplantation diabetes mellitus (PTDM) after renal transplantation, which is associated with cardiovascular events. Although PTDM is triggered by immunosuppressive agents (calcineurin inhibitors, glucocorticoids), there is consensus against switching patients from potent tacrolimus to the less diabetogenic cyclosporin. Full-blown PTDM must therefore be treated aggressively. Empagliflozin inhibits sodium-glucose cotransporter 2 in the proximal tubule of the kidney and dramatically reduced cardiovascular risk in type 2 diabetics in a recent randomized trial. Especially in diabetics with impaired renal function, empagliflozin was safe, well tolerated, and effective against hyperglycemia and against high blood pressure. Data on SGLT2 inhibition after transplantation are completely lacking. Therefore, the potential antidiabetic of choice is currently withheld from the vulnerable PTDM population. METHODS, STUDY DESIGN: Prospective, single-center, non-inferiority study. Inclusion criteria: PTDM (antidiabetic therapy ≥6 months, based on prior 2-h BG ≥200 mg/dL, fasting BG ≥125 mg/dL (2 times) or HbA1c ≥6.5%); stable renal allograft function \>6 months; eGFR ≥30 mL/min/1.73m2. Most important exclusion criteria: type 1 and 2 diabetes; insulin demand \>40 IU/day; HbA1c \>8.5%. After study inclusion, patients will record 4 weeks of 4-times daily BG measurements before undergoing an OGTT, lab work and urine analysis (including ketones, urinary culture). Empagliflozin (10 mg) will be started and insulin discontinued within 3 days. Patients will be asked to perform urinary dipstick tests at home (i.e. ketones), and to continue recording BG. Study visits at 2 and 4 weeks (second OGTT + lab work (as above)). If control over hyperglycemia is insufficient, insulin therapy will be added back, otherwise study patients remain on empagliflozin monotherapy for 1 year. Statistics will include the paired t-test.

Conditions

Posttransplant Diabetes Mellitus

Keywords

Empagliflozin; SGLT-2 Inhibition; Glucose Metabolism

Outcome Measures

Primary Outcomes (1)

• OGTT-derived 2-hour blood glucose level

  Mean change from baseline blood glucose levels of the 2h value after OGTT (75g glucose) after 1 month of empagliflozin monotherapy. Maximum tolerable change from baseline blood glucose levels should not exceed 30 mg/dL on average (100 mg/dL in each individual).

  4 weeks after start of Empagliflozin treatment

Study Arms (1)

Empagliflozin Arm

OTHER

Posttransplant Diabetes Mellitus (PTDM) patients after kidney transplantation receiving Empagliflozin 10 MG \[Jardiance\]

Drug: Empagliflozin 10 mg

Interventions

Empagliflozin 10 mg DRUG

PTDM patients on previous antidiabetic treatment (\<40 IU insulin (in some cases plus oral antidiabetics)) receive Empagliflozin, ideally as monotherapy

Also known as: Jardiance

Empagliflozin Arm

Eligibility Criteria

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

You may qualify if:

• Diagnosed PTDM defined as: A transplant patient requiring antidiabetic therapy, based on a previous 2-hour plasma glucose level ≥ 200 mg/dL in the OGTT (75mg glucose), based on previous blood glucose levels ≥ 200 mg/dL during random controls or based on fasting glucose levels ≥ 125 mg/dL twice or HbA1c ≥ 6.5%
• Stable graft function for more than 6 months post transplantation (eGFR ≥ 30 ml/min/1.73m2)
• At least 6 months of standard of care antidiabetic therapy (usually basal insulin) for PTDM

You may not qualify if:

• Age\< 18 years
• Patients with prior history of type 1 or type 2 diabetes
• Pregnancy
• Severe renal impairment (GFR \< 30 mL/min./1.73 m2)
• Severe blood glucose elevation with the need for therapy with insulin \> 40 IU/day or HbA1c \>8.5%

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Austria

Vienna, 1090, Austria

Location

Related Publications (1)

• Schwaiger E, Burghart L, Signorini L, Ristl R, Kopecky C, Tura A, Pacini G, Wrba T, Antlanger M, Schmaldienst S, Werzowa J, Saemann MD, Hecking M. Empagliflozin in posttransplantation diabetes mellitus: A prospective, interventional pilot study on glucose metabolism, fluid volume, and patient safety. Am J Transplant. 2019 Mar;19(3):907-919. doi: 10.1111/ajt.15223. Epub 2019 Jan 25.

  PMID: 30585690 DERIVED

MeSH Terms

Interventions

empagliflozin

Study Officials

• Manfred Hecking, MD

  Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Austria

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc. Prof. PD. Dr.med.

Study Record Dates

• First Submitted: April 8, 2017
• First Posted: April 13, 2017
• Study Start: January 15, 2017
• Primary Completion: June 13, 2017
• Study Completion: May 31, 2018
• Last Updated: May 7, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)