SGLT2 Inhibitors for Metabolic Diseases

(INFORM_2 Trial)

Overseen By Sarah Chu, NP

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must not be taking: SGLT2 inhibitors, Steroids

Disqualifiers: Type 1 diabetes, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 24 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how SGLT2 inhibitors, a class of medications that lower blood sugar levels, might improve blood flow in the heart's arteries for women living with HIV. The focus is on women who also have diabetes, chronic kidney disease, or both, but have not experienced a heart attack. Participants will receive either health education alone or health education plus a referral to a specialist who might prescribe SGLT2 inhibitors. Women with HIV on stable treatment who have diabetes, kidney issues, or specific heart blood flow concerns may be suitable for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

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 participate if you are currently using SGLT2 inhibitors or certain systemic steroids or immune suppressant therapies.

Is there any evidence suggesting that SGLT2 inhibitors are likely to be safe for humans?

Research has shown that SGLT2 inhibitors are generally safe for individuals with diabetes or chronic kidney disease. These medications can protect the kidneys and reduce the risk of heart problems. For instance, one study found that empagliflozin, a type of SGLT2 inhibitor, lowered the chance of kidney disease worsening or death from heart issues.

Another study found that SGLT2 inhibitors might reduce the risk of sudden kidney problems. They are considered safe, especially for individuals with chronic kidney disease, even if they don't have diabetes.

These findings suggest that SGLT2 inhibitors are usually well-tolerated and safe. However, discussing any new treatment with a healthcare provider is always important to understand personal risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about SGLT2 inhibitors because they offer a unique approach to treating metabolic diseases like diabetes and chronic kidney disease. Unlike many current treatments that primarily focus on managing blood sugar or blood pressure, SGLT2 inhibitors work by blocking a protein in the kidneys, which helps the body remove excess glucose through urine. This mechanism not only helps in controlling blood sugar levels but also provides protective benefits for the kidneys and heart. These dual benefits make SGLT2 inhibitors a promising option, potentially enhancing patient outcomes beyond what standard treatments can achieve.

What evidence suggests that SGLT2 inhibitors might be an effective treatment for improving blood flow in women with HIV and either diabetes or chronic kidney disease?

Research has shown that SGLT2 inhibitors can help people with chronic kidney disease (CKD) and type 2 diabetes. These treatments slow the progression of CKD and reduce the risk of heart problems. Studies have demonstrated that patients using SGLT2 inhibitors experience improved kidney function over time. This medication is already approved for people with diabetes and CKD, confirming its benefits. In this trial, one group of participants will receive health education plus a referral for consideration of SGLT2 inhibitor therapy, while another group will receive health education alone. For women with HIV who also have diabetes or CKD, these benefits might include improved blood flow in the heart's arteries, which is a main focus of this study. ^{1 4 6 7 8}

Who Is on the Research Team?

Markella V Zanni, MD

Principal Investigator

MGH/HMS

Are You a Good Fit for This Trial?

This trial is for women with HIV and either diabetes, chronic kidney disease, or both. Participants should not have a history of heart attacks. The study aims to help those who may be underusing SGLT2 inhibitors—a medication that could improve their coronary blood flow.

Inclusion Criteria

I was born female.

Coronary flow reserve <2.5 on screening cardiac positron emission tomography/computed tomography

I am between 45 and 75 years old.

Exclusion Criteria

Uncontrolled hypertension at screen, defined as systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg

Hemoglobin A1c ≥8.5% at screen

I have a history of heart failure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive health education and may be referred to a subspecialty clinic for consideration of SGLT2 inhibitor therapy

24 weeks

Regular visits as per clinical care

Follow-up

Participants are monitored for changes in coronary flow reserve and other biomarkers

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• SGLT2 Inhibitors

Trial Overview The study tests if health education combined with referral to an Endocrinologist or Nephrologist and potential treatment with SGLT2 inhibitors can enhance coronary blood flow in women with HIV and metabolic disorders. It's a randomized trial comparing the effects of just health education versus additional specialist care.

How Is the Trial Designed?

Group I: Health education plus subspecialty clinic referral for consideration of SGLT2 inhibitor therapy Experimental Treatment 1 Intervention

Participants randomized to this study arm will receive health education and will be referred to establish clinical care in either the MGH Lipid and Metabolism Clinic or the MGH Renal Clinic for consideration of SGLT2 inhibitor therapy. By study design (inclusion criteria), participants will have a clinical indication for SGLT2 inhibitor therapy (either diabetes or chronic kidney disease). SGLT2 inhibitor therapy (e.g. empagliflozin 10 mg by mouth daily or dapagliflozin 10 mg by mouth daily) may or may not be prescribed by the subspecialty clinician as part of routine clinical care, according to the clinician's clinical judgement. Participants will also receive health education.

Group II: Health Education Experimental Treatment 2 Interventions

Participants randomized to this study arm will receive health education alone.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

SGLT2 inhibitors, a new class of oral medications for type 2 diabetes, effectively lower blood glucose levels by preventing the reabsorption of glucose and sodium in the kidneys, and they also provide cardiovascular and renal protection.

While SGLT2 inhibitors are generally well-tolerated, they carry risks of serious side effects such as hypoglycemia, hypotension, and infections, necessitating careful patient monitoring to manage these potential complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of sodium glucose co-transporter 2 (SGLT2) inhibitors: A brief summary. Mascolo, A., Di Napoli, R., Balzano, N., et al.[2022]

A review of 47 systematic reviews on SGLT-2 inhibitors found that most had low methodological quality, leaving uncertainty about the risks of important side effects in patients with type 2 diabetes.

Canagliflozin and dapagliflozin were linked to an increased risk of genital infections and diabetic ketoacidosis, while dapagliflozin also showed a significant risk for urinary tract infections; however, no SGLT-2 inhibitors were associated with a significant increase in acute kidney injury or bone fractures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events associated with sodium glucose co-transporter 2 inhibitors: an overview of quantitative systematic reviews. Pelletier, R., Ng, K., Alkabbani, W., et al.[2022]

SGLT2 inhibitors, like dapagliflozin, help lower blood sugar levels by increasing glucose excretion in urine, working independently of insulin, which is a unique mechanism among diabetes medications.

Clinical trials and real-life studies show that dapagliflozin not only improves glycemic control by reducing glycosylated hemoglobin but also contributes to weight loss and lower blood pressure, offering additional metabolic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Impact of dapagliflozin on cardiovascular risk factors. Beyond glycemic control]. Pallarés, V., Escobar, C., Egocheaga, I., et al.[2021]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2024816

Dapagliflozin in Patients with Chronic Kidney Disease The kidney-protective effects of SGLT2 inhibitors have previously been shown in patients with type 2 diabetes and chronic kidney disease in the CREDENCE trial.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9217649/

A real-world study on SGLT2 inhibitors and diabetic kidney ... This real-world study demonstrates the benefits of SGLT2is on CKD progression and ESKD. The effect is more pronounced in moderate to advanced CKD patients.

3. academic.oup.com academic.oup.com/ndt/article/40/10/1838/8063570

SGLT2 inhibitors in CKD: are they really effective in all patients? Sodium-glucose cotransporter 2 (SGLT2) inhibitors effectively slow chronic kidney disease (CKD) progression and reduce cardiovascular events.

4. dmsjournal.biomedcentral.com dmsjournal.biomedcentral.com/articles/10.1186/s13098-024-01547-x

Evaluating the overall renal outcomes of sodium-glucose ... The results of our meta-analysis showed that after 64 weeks of treatment, SGLT2 inhibitors showed a significant benefit on eGFR rate with no further decline ...

5. diabetesjournals.org diabetesjournals.org/care/article/44/11/2542/138505/Kidney-Outcomes-Associated-With-SGLT2-Inhibitors

Kidney Outcomes Associated With SGLT2 Inhibitors Versus ... Using data from the J-CKD-DB, we compared the rate of eGFR decline and kidney outcomes between T2DM and CKD patients initiating SGLT2 ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0168822725003523

Mortality, kidney, and safety outcomes with SGLT2 ... A 2024 study, using data from the TriNetX network, found that in patients with type 2 diabetes and a history of kidney transplantation, SGLT2 inhibitors use ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa2204233

Empagliflozin in Patients with Chronic Kidney Disease Empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo.

8. nature.com nature.com/articles/s41598-025-86172-y

Real-world effectiveness and safety of sodium-glucose co ... These findings suggest SGLT2i therapy might reduce adverse kidney outcomes in CKD patients, regardless of diabetic status, with a favorable safety profile.