SeMaglutide and Albuminuria Reduction Trial in Obese Individuals Without Diabetes

Conditions

Albuminuria, Obesity

Keywords

SMART, Semaglutide, UMCG, Lambers Heerspink

Brief summary

Study to assess the effects of weekly subcutaneous administration of the GLP1-RA semaglutide 2.4mg on kidney function parameters in obese/overweight individuals at high risk of CKD progression.

Detailed description

Glucagon Like Peptide 1 Receptor Agonist (GLP1-RA) therapies have been introduced as antidiabetic drugs. In addition, GLP1-RA therapies reduce body weight, in patients with and without diabetes, without inducing hypoglycemia. Moreover, GLP1-RA reduce albuminuria in patients with type 2 diabetes, and liraglutide and semaglutide have been shown to improve various risk markers of CKD progression in non-diabetic obese individuals. It is therefore likely that these agents delay progression of kidney function decline in high risk obese/overweight, non-diabetic individuals. The main objective of the study is to assess the albuminuria lowering effects of semaglutide 2.4 mg s.c. once weekly (Semaglutide 3 mg/ml) compared to placebo in obese/overweight non-diabetic individuals with elevated albuminuria. This will be tested in a 24-week randomized placebo controlled double-blind two arm parallel clinical trial with a 4 week wash-out period after 24 weeks double blind treatment to assess off drug effects.

Apperloo EM, Gorriz JL, Soler MJ, Cigarrán Guldris S, Cruzado JM, Puchades MJ, López-Martínez M, Waanders F, Laverman GD, van der Aart-van der Beek A, Hoogenberg K, van Beek AP, Verhave J, Ahmed SB, Schmieder RE, Wanner C, Cherney DZI, Jongs N, Heerspink HJL.

2024-10-2551 citations

10.1038/s41591-024-03327-6

Long-term kidney outcomes of semaglutide in obesity and cardiovascular disease in the SELECT trial.

Colhoun HM, Lingvay I, Brown PM, Deanfield J, Brown-Frandsen K, Kahn SE, Plutzky J, Node K, Parkhomenko A, Rydén L, Wilding JPH, Mann JFE, Tuttle KR, Idorn T, Rathor N, Lincoff AM.

2024-05-25127 citations

10.1038/s41591-024-03015-5

Effects of Semaglutide on Albuminuria and Kidney Function in People With Overweight or Obesity With or Without Type 2 Diabetes: Exploratory Analysis From the STEP 1, 2, and 3 Trials

Hiddo J.L. Heerspink, Ellen M. Apperloo, Melanie J. Davies, Dror Dicker, Kristian Kandler et al. (10 authors)

Diabetes Care2023-02-1784 citations

10.2337/dc22-1889

Interventions

DRUGSemaglutide

Patients will be treated for 24 weeks with semaglutide 3.0 mlg/ml s.c. once weekly. The starting dose of semaglutide will be 0.24 mg per week subcutaneous injection with increasing doses at 4, 8, 12, and 16 weeks to 0.5, 1,0, 1.7 and 2.4 mg.

DRUGPlacebo

Patients will receive a matching placebo sc. once weekly during the treatment period of 24 weeks.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Intervention model description

Randomized placebo controlled double-blind two arm parallel clinical trial

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* Age ≥ 18 years * Body Mass index ≥ 27 kg/m2 * Albuminuria ≥ 30 mg/g and ≤ 3500 mg/g * eGFR ≥ 25 ml/min/1.73m2 * Stable renal function prior to entry into the study defined as no more than 30% eGFR change in 3 months prior to enrolment * Signed Informed Consent

Exclusion criteria

* Diagnosis with type 1 or type 2 Diabetes * Hba1c ≥ 6.5% at screening * Cardiovascular disease event in 3 months prior to enrollment * Treatment with GLP-1 RA \< 4 weeks prior to screening * Uncontrolled thyroid disease TSH\>6.0 mIU/L or \<0.4 mIU/L at screening * Acute pancreatitis \< 180 days prior to screening * History or presence of chronic pancreatitis * Females of child-bearing potential who are pregnant, breast-feeding or have intention of becoming pregnant or are not using adequate contraceptive measures

Design outcomes

Primary

Measure	Time frame	Description
Change from baseline to week 24 in urinary albumin:creatinine ratio (UACR)	Week 1 to week 24	Measured in first morning void

Secondary

Measure	Time frame	Description
Iohexol measured glomerular filtration rate (GFR)	Week 1 to week 24	Change from baseline to week 24 in Iohexol measured glomerular filtration rate (GFR)
urinary albumin:creatinine ratio (UACR) during wash-out	week 24 to 28	Change in urinary albumin:creatinine ratio (UACR) during wash-out
estimated glomerular filtration rate (eGFR) during wash-out	week 24 to 28	Change in estimated glomerular filtration rate (eGFR) during wash-out
body weight	Week 1 to week 24	Change from baseline to week 24 in body weight
estimated glomerular filtration rate (eGFR)	Week 1 to week 24	Change from baseline to week 24 in estimated glomerular filtration rate (eGFR)
systolic and diastolic blood pressure	Week 1 to week 24	Change from baseline to week 24 in systolic and diastolic blood pressure
extracellular fluid	Week 1 to week 24	Change from baseline to week 24 in extracellular fluid as measured by bio-impedance
high sensitivity C-reactive protein (CRP)	Week 1 to week 24	Change from baseline to week 24 in high sensitivity C-reactive protein (CRP)
hip circumference	Week 1 to week 24	Change from baseline to week 24 in hip circumference

Countries

Canada, Germany, Netherlands, Spain

Outcome results

None listed