Please select the arm or intervention descriptions that belong to the clinical trial below.
Title: Empagliflozin in Post-Transplantation Diabetes Mellitus
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.


Options:
A: Arm Label: Glucagon-like peptide-1 (GLP-1); Type: ACTIVE_COMPARATOR; Interventions: Dietary Supplement: Glucagon-like peptide-1 (GLP-1), Other: Hyperglycemic clamp | Arm Label: Isotonic saline; Type: PLACEBO_COMPARATOR; Interventions: Other: Isotonic saline, Other: Hyperglycemic clamp | Intervention Type: DIETARY_SUPPLEMENT; Name: Glucagon-like peptide-1 (GLP-1); Assigned to Arm(s): Glucagon-like peptide-1 (GLP-1) | Intervention Type: OTHER; Name: Isotonic saline; Assigned to Arm(s): Isotonic saline | Intervention Type: OTHER; Name: Hyperglycemic clamp; Assigned to Arm(s): Glucagon-like peptide-1 (GLP-1), Isotonic saline
B: Arm Label: Liraglutide; Type: EXPERIMENTAL; Interventions: Drug: liraglutide | Arm Label: Placebo; Type: PLACEBO_COMPARATOR; Interventions: Drug: placebo | Intervention Type: DRUG; Name: liraglutide; Assigned to Arm(s): Liraglutide | Intervention Type: DRUG; Name: placebo; Assigned to Arm(s): Placebo
C: Arm Label: Tight glucose control; Type: EXPERIMENTAL; Interventions: Drug: Insulin | Arm Label: Standard glucose control; Type: ACTIVE_COMPARATOR; Interventions: Drug: Insulin, Asp(B28)- | Intervention Type: DRUG; Name: Insulin; Assigned to Arm(s): Tight glucose control | Intervention Type: DRUG; Name: Insulin, Asp(B28)-; Assigned to Arm(s): Standard glucose control
D: Arm Label: Empagliflozin Arm; Type: OTHER; Interventions: Drug: Empagliflozin 10 mg | Intervention Type: DRUG; Name: Empagliflozin 10 mg; Assigned to Arm(s): Empagliflozin Arm

Answer: D