SLIMM + Semaglutide for Kidney Disease

Recruiting at 1 trial location

Overseen By Srinivasan Beddhu, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

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 This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

156 Participants Needed

What You Need to Know Before You Apply

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.

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 3 4 5}

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 6 7 8}

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. ^{2 3 4 6 9}

Who Is on the Research Team?

Srinivasan Beddhu, M.D.

Principal Investigator

University of Utah

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Guided Resistance Training
• Placebo
• Semaglutide
• SLIMM
• Standard Resistance Training

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.

How Is the Trial Designed?

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 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

Who Is Running the Clinical Trial?

Srinvasan Beddhu

Lead Sponsor

Trials

3

Recruited

290+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

Oral semaglutide, a GLP-1 analogue, showed consistent pharmacokinetics across various levels of renal impairment in a trial involving 71 subjects, indicating that kidney function does not significantly affect its absorption or metabolism.

The study found no safety concerns associated with oral semaglutide, and adverse events were similar to those seen with other GLP-1 receptor agonists, suggesting it is safe for use in patients with renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety and Tolerability of Oral Semaglutide in Subjects with Renal Impairment. Granhall, C., Søndergaard, FL., Thomsen, M., et al.[2021]

In a study involving 56 subjects with varying degrees of renal impairment, semaglutide exposure was found to be similar in those with mild to moderate renal impairment and end-stage renal disease compared to those with normal kidney function, suggesting it is safe for use in these populations.

The drug was well-tolerated overall, with no significant safety concerns or serious adverse events reported, indicating that dose adjustments for semaglutide may not be necessary for patients with renal impairment.

NCBI (Pubmed)

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. Marbury, TC., Flint, A., Jacobsen, JB., et al.[2018]

In a study involving 486 type 2 diabetes patients, semaglutide was found to be effective in improving glycemic control and achieving weight loss, with no significant differences in efficacy between patients with chronic kidney disease (CKD) and those without.

The treatment was safe for all patients, and CKD severity did not notably affect the treatment response, suggesting that semaglutide can be effectively used in managing type 2 diabetes in patients with varying levels of kidney function.

NCBI (Pubmed)

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. García de Lucas, MD., Caballero, I., Fernández-García, JC., et al.[2023]

In a post-hoc analysis of 8416 patients with type 2 diabetes from multiple trials, semaglutide initially caused a decline in estimated glomerular filtration rate (eGFR), but this decline plateaued over time, indicating no long-term adverse effects on kidney function compared to placebo.

Semaglutide significantly reduced urinary albumin-to-creatinine ratio (UACR), suggesting improved kidney health, and there was no increase in kidney-related adverse events compared to other treatments, highlighting its safety and efficacy in managing kidney function in diabetic patients.

NCBI (Pubmed)

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. Mann, JFE., Hansen, T., Idorn, T., et al.[2020]

Subcutaneous semaglutide (Ozempic®), a GLP-1 receptor agonist, has shown significant efficacy in improving glycemic control and reducing HbA1c, albuminuria, and blood pressure in patients with advanced diabetic kidney disease (DKD) during a 6-month follow-up study involving patients on maintenance hemodialysis.

The treatment not only aids in weight loss and appetite suppression but also helps preserve residual kidney function, potentially improving patient outcomes and facilitating their inclusion on kidney transplant waiting lists.

NCBI (Pubmed)

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. De la Flor, JC., Lorenzo, JD., Marschall, A., et al.[2022]

Oral semaglutide (Rybelsus®) has been shown to provide better glycaemic control and promote weight loss in patients with type 2 diabetes (T2DM) compared to standard oral glucose-lowering medications, based on data from the PIONEER clinical trial program involving 9543 patients.

The safety profile of oral semaglutide is similar to other GLP-1 receptor agonists, and it demonstrated cardiovascular safety comparable to placebo in high-risk patients, making it a viable option for T2DM management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. Paquot, N.[2022]

Semaglutide (Ozempic®) is an effective once-weekly treatment for type 2 diabetes, showing superior glucose-lowering effects and greater weight loss compared to other GLP-1 receptor agonists in Phase III clinical trials.

It is approved for use in Belgium for patients with type 2 diabetes who have not achieved adequate control with other antidiabetic therapies, particularly in those with a body mass index of 30 kg/m² or higher.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Semaglutide, once weekly GLP-1 receptor agonist (Ozempic®)]. Scheen, AJ.[2019]

In a study involving diabetic db/db mice with advanced diabetic kidney disease (DKD), the GLP-1 receptor agonist semaglutide significantly reduced hyperglycemia, hypertension, and albuminuria, while improving kidney health markers such as glomerulosclerosis and podocyte density.

The combination of semaglutide with the ACE inhibitor lisinopril provided additional benefits in managing hypertension and kidney damage, suggesting that semaglutide could be an effective treatment option for patients with DKD.

NCBI (Pubmed)

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. Dalbøge, LS., Christensen, M., Madsen, MR., et al.[2022]

In the STEP 2 trial involving 1,205 participants, semaglutide (both 1.0 mg and 2.4 mg) significantly improved kidney function as measured by urine albumin-to-creatinine ratio (UACR), with reductions of -14.8% and -20.6% respectively, compared to an increase of +18.3% in the placebo group.

Across pooled data from STEP 1-3, semaglutide did not affect estimated glomerular filtration rate (eGFR) decline in participants with normal kidney function, indicating its safety in terms of kidney function preservation.

NCBI (Pubmed)

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. Heerspink, HJL., Apperloo, E., Davies, M., et al.[2023]

Citations

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

Pharmacokinetics, Safety and Tolerability of Oral Semaglutide in Subjects with Renal Impairment. [2021]

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]

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]

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]

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]

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

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. [2022]

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

[Semaglutide, once weekly GLP-1 receptor agonist (Ozempic®)]. [2019]

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]

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]