Idorn 2013.

Methods	Study design: parallel RCT Study time frame: not reported Duration of follow‐up: 12 weeks
Participants	Country: Denmark Setting: multicentre (2 centres) Inclusion criteria: 2 groups of patients ‐ ESKD (Group 1) and normal kidney function (Group 2) Group 1: Patients aged 18 to 85 years receiving chronic HD or PD; type 2 DM diagnosed at least 3 months prior to screening; preserved beta‐cell function as evaluated by a glucagon test Group 2: Patients aged 18 to 85 years with normal kidney function (SCr < 105 µmol/L for men and < 90 µmol/L for women); type 2 DM diagnosed at least 3 months prior to screening; HbA1c > 6.5% (> 48 mmol/mol); preserved beta‐cell function as evaluated by a glucagon test Number (randomised/analysed) Group 1: treatment group (14/10); control group (10/10) Group 2: treatment group (11/10); control group (12/10) Mean age ± SE (years) Group 1: treatment group (68.3 ± 3.1); control group (65.9 ± 4.4) Group 2: treatment group (60.7 ± 3.2); control group (63.1 ± 2.1) Sex (M/F) Group 1: treatment group (8/2); control group (9/1) Group 2: treatment group (7/3); control group (8/2) Exclusion criteria: type 1 DM; chronic pancreatitis or previous acute pancreatitis; known or suspected hypersensitivity to trial product(s) or related products; treatment with oral glucocorticoids, calcineurin inhibitors; dipeptidyl peptidase 4 inhibitors or other drugs, which in the investigator’s opinion could interfere with glucose or lipid metabolism 90 days prior to screening; cancer (except BCC or squamous cell skin cancer) or any other clinically significant disorder, which in the investigator’s opinion could interfere with the results of the trial; inflammatory bowel disease; cardiac disease defined as heart failure (NYHA Class III–IV) and/or diagnosis of unstable angina pectoris and/or myocardial infarction within the last 6 months; BMI ≤18.5 or ≥ 50.0 kg/m2; women of childbearing potential who are pregnant, breastfeeding, intend to become pregnant or not using adequate contraceptive methods; clinical signs of diabetic gastroparesis; impaired liver function (ALT > twice upper reference level); use of any investigational product 90 days prior to this trial; known or suspected abuse of alcohol or narcotics; screening plasma calcitonin ≥ 50 ng/L; personal or family history of medullary thyroid carcinoma or a personal history of multiple endocrine neoplasia type 2
Interventions	Treatment group SC Liraglutide: 0.6 mg once/d for 12 weeks. All participants were requested to inject the medicine in the abdomen before breakfast. Control group Placebo: once/d for 12 weeks. All participants were requested to inject the medicine in the abdomen before breakfast Other information Depending on glycaemic control and adverse effects, dose was escalated by up to 0.6 mg/week to a maximum 1.8 mg Doses of baseline antidiabetic medication were individually adjusted in parallel with study medication according to prespecified treatment goals. To minimize risk of hypoglycaemia, basal insulin dose reduced by 20‐50% at randomisation and suIphonylureas were paused, while metformin was continued in unchanged doses
Outcomes	Dose corrected trough concentration of liraglutide in plasma at the final study visit (week 12) Severe adverse events, Adverse effects, glycaemic control, change in baseline insulin, body weight, hypoglycaemic episodes (divided into minor blood glucose < 3.1 mmol/L and no need assistance) and major (blood glucose < 3.1 mmol/L and requiring assistance from third person) Cardiovascular parameters: heart rate, BP, and prohormone brain natriuretic peptide concentration in plasma
Notes	Only Group 1 (ESKD patients) was included in this systematic review Funding source: Novo Nordisk
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	“Patients and control subjects were assigned to receive either liraglutide or pIacebo according to a computer‐generated randomisation list provided by Novo Nordisk”.
Allocation concealment (selection bias)	Low risk	“Patients and control subjects were assigned to receive either liraglutide or pIacebo according to a computer‐generated randomisation list provided by Novo Nordisk”.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	“Participants, Investigators, and healthcare staff were blinded for the allocated treatment and remained so until the last patient’s last visit”.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	“Participants, Investigators, and healthcare staff were blinded for the allocated treatment and remained so until the last patient’s last visit”.
Incomplete outcome data (attrition bias) All outcomes	High risk	5/14 35% liraglutide group; 0/10 0% control group discontinued for the ESKD group.
Selective reporting (reporting bias)	Low risk	The prespecified outcomes were available on a clinical trials database and major outcomes were reported.
Other bias	High risk	Conflicts of interest: Novo Nordisk sponsored the study although the company did not participate in writing the protocol, collection, analysis and interpretation of data or writing the manuscript. All authors have either received research support, are on the advisory board, or hold shares with Novo Nordisk. Study was mildly underpowered: Based on the primary end point and with a liraglutide trough value of 20 000 pmol/L during steady state and standard deviation estimated to be 8000 pmol/L in people with normal kidney function, 10 completers in each liraglutide treatment arm and an α = 0.05 would enable the investigators to detect a difference of 10,600 pmol/L with a power of 80% (1‐ β = 0.80) using a 2 sample Student t‐test. In the ESKD arm, 9 patients completed the study.