SLIMM + Semaglutide for Kidney Disease

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Srinivasan Beddhu, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Srinvasan Beddhu

Must be taking: Semaglutide

Must not be taking: GLP-1 receptor agonists

Disqualifiers: Type 1 diabetes, Bariatric surgery, Heart failure, others

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use any GLP-1 receptor agonist within 30 days before joining the study.

What data supports the effectiveness of the drug semaglutide for kidney disease?

Research shows that semaglutide, a drug used for type 2 diabetes, can help slow the progression of kidney disease by improving blood sugar control, reducing blood pressure, and decreasing protein in the urine. It also helps with weight loss, which can be beneficial for kidney health. ^{1 2 3 4 5}

Is semaglutide safe for humans?

Semaglutide, used for type 2 diabetes, has been shown to be generally safe in humans, including those with kidney issues, with common side effects like nausea and vomiting. It has been tested in various forms, such as oral and injectable, and is considered safe for people with advanced kidney disease. ^{1 2 5 6 7}

How is the drug Semaglutide unique for treating kidney disease?

Semaglutide is unique for treating kidney disease because it is a once-weekly injection that not only helps control blood sugar levels but also shows potential benefits for kidney health, such as reducing albuminuria (protein in urine) and preserving kidney function, which are not typical effects of standard diabetes medications. ^{3 5 7 8 9}

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

Access to compatible "smartphone" or device (i.e., Android, Kindle or Apple with internet connectivity or mobile network), desktop or laptop

I can walk between 300 to 600 meters in six minutes.

My kidney function is moderately to severely reduced.

Exclusion Criteria

Vulnerable populations- pregnant or incarcerated

I use supplemental oxygen during the day.

I use devices like canes or walkers to help me move around.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

SLIMM Intervention

Participants undergo the SLIMM intervention targeting sedentary behavior

3 months

Extended Intervention

Participants continue with SLIMM, resistance training, and either placebo or semaglutide

9 months

Follow-up

Participants are monitored for changes in sleep, quality of life, inflammation markers, and physical performance

12 months

Treatment Details

Interventions

• Guided Resistance Training (Behavioral)
• Placebo (Drug)
• Semaglutide (GLP-1 Receptor Agonist)
• SLIMM (Behavioral)
• Standard Resistance Training (Behavioral)

Trial Overview 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.

Participant Groups

Group I: SLIMM + Guided RT + Semaglutide Experimental Treatment 3 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 + Placebo Active Control 3 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 + Placebo Placebo Group 3 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 Nearby Select from list below to view details:

Stanford University Stanford, CA

University of Utah Salt Lake City, UT

Who Is Running the Clinical Trial?

Srinvasan Beddhu Lead Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Collaborator

Stanford University Collaborator

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

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.

2. Switzerland pubmed.ncbi.nlm.nih.gov

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).

3. Switzerland pubmed.ncbi.nlm.nih.gov

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.

4. England pubmed.ncbi.nlm.nih.gov

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.

5. Switzerland pubmed.ncbi.nlm.nih.gov

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.

6. Belgium pubmed.ncbi.nlm.nih.gov

[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.

7. Belgium pubmed.ncbi.nlm.nih.gov

[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.

8. Switzerland pubmed.ncbi.nlm.nih.gov

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.

9. United States pubmed.ncbi.nlm.nih.gov

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.