SLIMM + Semaglutide for Kidney Disease
Palo Alto (17 mi)Overseen bySrinivasan Beddhu, M.D.
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Srinvasan Beddhu
Prior Safety Data
Trial Summary
What is the purpose of this trial?* Prolonged sitting (sedentary behavior) is a risk factor for decreased kidney function, obesity, diabetes and mortality. Prolonged sitting is associated with decreased kidney function and increased risk of diabetes, heart disease and death.
* In a previous pilot study funded by NIH, it was shown that a Sit Less, Interact and Move More (SLIMM) intervention targeting sedentary behavior in people with kidney disease was able to decrease prolonged sitting but that effect was not sustained.
* Therefore, the researchers are currently conducting a follow-up study named Sit Less, Interact and Move More (SLIMM) 2.
* This NIH funded study is conducted at the University of Utah and Stanford University.
* The purpose of this study is to see if guided resistance training (to improve muscle strength) and semaglutide (FDA approved diabetes and weight loss medication that might also improve physical function) can boost adherence to the SLIMM Intervention and reduce sedentary behavior.
What data supports the idea that SLIMM + Semaglutide for Kidney Disease is an effective treatment?The available research shows that semaglutide, a drug used in combination with SLIMM, is effective in managing kidney disease in patients with type 2 diabetes. It helps improve blood sugar control, reduces weight, and lowers blood pressure. In a study with patients undergoing hemodialysis, semaglutide showed positive effects on kidney function, helping to maintain their current treatment schedule and potentially allowing them to be considered for kidney transplants. This suggests that semaglutide can be a beneficial part of treatment for kidney disease.12479
Is the drug Semaglutide a promising treatment for kidney disease?Yes, Semaglutide shows promise as a treatment for kidney disease. It helps control blood sugar levels, reduces weight, and has positive effects on kidney health, such as lowering blood pressure and reducing kidney damage. These benefits could improve the health of people with kidney disease and potentially help them qualify for kidney transplants.36789
What safety data exists for SLIMM + Semaglutide in kidney disease treatment?The safety of semaglutide, a GLP-1 receptor agonist, has been evaluated in various forms, including oral (Rybelsus®) and subcutaneous (Ozempic®) administration. Clinical trials, such as the PIONEER and SUSTAIN programs, have demonstrated its safety and efficacy in managing type 2 diabetes, with a tolerability profile consistent with other GLP-1 RAs. In patients with renal impairment, studies have shown that semaglutide is safe and well-tolerated, with beneficial effects on glycemic control, weight loss, and kidney function. However, specific studies on semaglutide's safety in renal replacement therapy are limited. Overall, semaglutide is considered safe for use in patients with advanced chronic kidney disease, with approval for use down to an eGFR of 15 mL/min/1.73 m2.12357
Do I have to stop taking my current medications for the trial?The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use any GLP-1 receptor agonist within 30 days prior to screening.
Eligibility Criteria
The SLIMM 2 study is for adults with chronic kidney disease who are overweight, can walk a certain distance, and have moderate to severe reduction in kidney function. Participants need internet access and the ability to do resistance training but cannot be on oxygen therapy or have had recent major medical procedures.Inclusion Criteria
I can walk between 300 to 600 meters in six minutes.
My kidney function is moderately to severely reduced.
Exclusion Criteria
I use supplemental oxygen during the day.
I use devices like canes or walkers to help me move around.
I am currently participating in a trial that involves new drugs or devices.
I don't have a history of pancreatitis or thyroid cancer in my family.
I am unable to understand and give consent for treatment.
I haven't used any GLP-1 receptor agonists in the last 30 days.
I am currently diagnosed with the most severe heart failure.
I have had weight loss surgery in the past.
My cancer has spread to other parts of my body.
Treatment Details
This trial tests whether guided resistance training and semaglutide (a diabetes/weight loss medication) can help people with kidney disease reduce sedentary behavior by improving muscle strength and physical function as part of the SLIMM intervention.
3Treatment groups
Experimental Treatment
Active Control
Placebo Group
Group I: SLIMM + Guided RT + SemaglutideExperimental Treatment3 Interventions
SLIMM intervention for 3 months, followed by a 9-month intervention of SLIMM, guided resistance training and oral semaglutide
Group II: SLIMM + Guided RT + PlaceboActive Control3 Interventions
SLIMM intervention for 3 months, followed by a 9-month intervention of SLIMM, guided resistance training and oral placebo
Group III: SLIMM + Standard RT + PlaceboPlacebo Group3 Interventions
SLIMM intervention for 3 months, followed by a 9-month intervention of SLIMM, standard-of-care resistance training and oral placebo
Semaglutide is already approved in European Union, United States, Canada, Japan, United States, United States for the following indications:
🇪🇺 Approved in European Union as Ozempic for:
- Type 2 diabetes
- Cardiovascular disease
- Obesity
🇺🇸 Approved in United States as Ozempic for:
- Type 2 diabetes
- Cardiovascular disease
- Obesity
🇨🇦 Approved in Canada as Ozempic for:
- Type 2 diabetes
- Cardiovascular disease
- Obesity
🇯🇵 Approved in Japan as Ozempic for:
- Type 2 diabetes
- Cardiovascular disease
- Obesity
🇺🇸 Approved in United States as Wegovy for:
- Obesity
🇺🇸 Approved in United States as Rybelsus for:
- Type 2 diabetes
Find a clinic near you
Research locations nearbySelect from list below to view details:
Stanford UniversityStanford, CA
University of UtahSalt Lake City, UT
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Who is running the clinical trial?
Srinvasan BeddhuLead Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Collaborator
Stanford UniversityCollaborator
References
Pharmacokinetics and Tolerability of a Single Dose of Semaglutide, a Human Glucagon-Like Peptide-1 Analog, in Subjects With and Without Renal Impairment. [2018]The pharmacokinetics and tolerability of semaglutide, a once-weekly human glucagon-like peptide-1 analog in development for the treatment of type 2 diabetes mellitus, were investigated in subjects with/without renal impairment (RI).
Pharmacokinetics, Safety and Tolerability of Oral Semaglutide in Subjects with Renal Impairment. [2021]Semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, has been co-formulated with the absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC) as a tablet for oral administration. This trial (NCT02014259) investigated the pharmacokinetics, safety and tolerability of oral semaglutide in subjects with and without renal impairment.
[Semaglutide, once weekly GLP-1 receptor agonist (Ozempic®)]. [2019]Semaglutide (Ozempic®) is a new once-weekly agonist of glucagon-like peptide-1 receptors (GLP-1 AR) indicated in the treatment of type 2 diabetes (T2D). Phase III clinical trials of the SUSTAIN programme demonstrated both the efficacy and safety of semaglutide in patients with T2D treated by diet and exercise, oral antidiabetic agents or even insulin. Direct and indirect comparative clinical trials showed that semaglutide (subcutaneous 0.5 or 1.0 mg once weekly) exerts a better glucose-lowering activity and a greater weight loss than other GLP-1 AR. Presented as prefilled pens for subcutaneous injection, semaglutide is currently reimbursed in Belgium after failure of antidiabetic therapy including metformin (HbA1c superior to 7,5 % or 58 mmol/mol) in T2D patients with body mass index ? 30 kg/m².
Effects of once-weekly subcutaneous semaglutide on kidney function and safety in patients with type 2 diabetes: a post-hoc analysis of the SUSTAIN 1-7 randomised controlled trials. [2020]Patients with type 2 diabetes have a high risk of developing chronic kidney disease. We examined the effects of semaglutide on kidney function and safety in a large, broad type 2 diabetes population.
[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. [2022]Oral semaglutide (Rybelsus®) is a co-formulation of semaglutide, a glucagon-like peptide-1 (GLP-1 RA) receptor agonist, with an absorption enhancer, sodium N- (8- [2- hydroxybenzoyl] amino) caprylate (SNAC), which facilitates the absorption of semaglutide across the gastric epithelium in a concentration dependent manner. The safety and efficacy of oral semaglutide were assessed in the PIONEER clinical trial programme, which included 9543 patients with type 2 diabetes (T2DM). Across a range of different T2DM patients receiving different background medications, oral semaglutide provides more effective glycaemic control than common oral glucose-lowering therapies, associated with a clinically relevant reduction in body weight, including in patients with more advanced T2DM on insulin treatment. The tolerability profile for oral semaglutide was consistent with the other GLP-1 RAs. Cardiovascular (CV) safety of oral semaglutide was noninferior to placebo in CV high-risk patients. Available in three doses (3, 7 and 14 mg) to be gradually increased, Rybelsus® is currently reimbursed in Belgium after failure of antidiabetic treatment (including metformin; HbA1C superior to 7.5 % or 58 mmol/mol) in T2DM patients with a body mass index ? 30 kg/m².
Nephroprotective Effects of Semaglutide as Mono- and Combination Treatment with Lisinopril in a Mouse Model of Hypertension-Accelerated Diabetic Kidney Disease. [2022]Background: Obesity, hyperglycemia and hypertension are critical risk factors for development of diabetic kidney disease (DKD). Emerging evidence suggests that glucagon-like peptide-1 receptor (GLP-1R) agonists improve cardiovascular and renal outcomes in type 2 diabetes patients. Here, we characterized the effect of the long-acting GLP-1R agonist semaglutide alone and in combination with an ACE inhibitor (lisinopril) in a model of hypertension-accelerated, advanced DKD facilitated by adeno-associated virus-mediated renin overexpression (ReninAAV) in uninephrectomized (UNx) female diabetic db/db mice. Methods: Female db/db mice received a single intravenous injection of ReninAAV 1 week prior to UNx. Six weeks post-nephrectomy, db/db UNx-ReninAAV mice were administered (q.d.) vehicle, semaglutide (30 nmol/kg, s.c.) or semaglutide (30 nmol/kg, s.c.) + lisinopril (30 mg/kg, p.o.) for 11 weeks. Endpoints included blood pressure, plasma/urine biochemistry, kidney histopathology and RNA sequencing. Results: Vehicle-dosed db/db UNx-ReninAAV mice developed hallmarks of DKD characterized by severe albuminuria and advanced glomerulosclerosis. Semaglutide robustly reduced hyperglycemia, hypertension and albuminuria concurrent with notable improvements in glomerulosclerosis severity, podocyte filtration slit density, urine/renal kidney injury molecule-1 (KIM-1) levels and gene expression markers of inflammation and fibrogenesis in db/db UNx-ReninAAV mice. Co-administration of lisinopril further ameliorated hypertension and glomerulosclerosis. Conclusions: Semaglutide improves disease hallmarks in the db/db UNx-ReninAAV mouse model of advanced DKD. Further benefits on renal outcomes were obtained by adjunctive antihypertensive standard of care. Collectively, our study supports the development of semaglutide for management of DKD.
Efficacy and Safety of Semaglutide, a Glucagon-Like Peptide-1 Receptor Agonist in Real-Life: A Case Series of Patients in Maintenance Incremental Hemodialysis. [2022]The glucagon-like peptide-1 receptor agonists (GLP-1RA) are among the newest treatment options available for managing of type 2 diabetes mellitus and slowing the progression of diabetes kidney disease (DKD). Subcutaneous (SC) semaglutide (Ozempic®) is a GLP-1RA with an extended half-life of approximately 1 week. GLP-1RA are highly effective in improving glycemic control and also show other beneficial effects such as increased natriuresis; decreased blood pressure and albuminuria; reduction of oxidative stress and inflammation; delay of gastric emptying and suppress appetite; the latter may result in significant weight loss. GLP-1RA can be used in patients with advanced-stage CKD; the European Medicines Agency has approved the use of all commercially available human GLP-1 analogs up to a minimal eGFR of 15 mL/min/1.73 m2. However, studies of safety and use of these agents in renal replacement therapy are scarce. Therefore, herein we present 3 cases of patients with advanced DKD in maintenance incremental hemodialysis with 1 session per week to describe the efficacy and safety of the SC semaglutide treatment and the favorable effects on glycemic control, lowering HbA1c, albuminuria, weight, blood pressure control, and preservation of residual kidney function (RKF) during a 6-month follow-up in a hospital hemodialysis unit in Spain. These effects could produce an improvement in morbidity and mortality and could also prevent albuminuria and preserve the RKF. This may allow our patients to maintain a weekly hemodialysis session and could facilitate their inclusion in the kidney transplant waiting lists.
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. [2023]These post hoc analyses of the Semaglutide Treatment Effect in People with obesity (STEP) 1-3 trials (NCT03548935, NCT03552757, and NCT03611582) explored the effects of semaglutide (up to 2.4 mg) on kidney function.
Influence of chronic kidney disease and its severity on the efficacy of semaglutide in type 2 diabetes patients: a multicenter real-world study. [2023]Semaglutide is a glucagon-like peptide 1 receptor agonist that improves glycemic control and achieves weight loss in type 2 diabetes (T2D) patients. Subcutaneous (s.c.) semaglutide at 1 mg once weekly (OW) is safe in T2D patients with chronic kidney disease (CKD). Whether or not CKD and its severity influence treatment response remains undetermined.