What side effects are associated with this type of intervention?

SGLT2 inhibitors, used in the treatment of Type 2 Diabetes, are associated with side effects such as an increased risk of urinary tract infections, genital mycotic infections, and a potential risk of ketoacidosis. There have also been concerns about an increased risk of lower limb amputations, particularly with canagliflozin. GLP-1 receptor agonists may cause gastrointestinal issues like nausea and vomiting, and there are concerns about pancreatitis and potential thyroid tumors. Insulin therapy can lead to hypoglycemia and weight gain. Patients should discuss these risks with their healthcare provider to determine the most appropriate treatment plan.

What prior FDA approvals exist?

The FDA has approved several SGLT2 inhibitors for the treatment of Type 2 Diabetes, including canagliflozin, dapagliflozin, and empagliflozin. These drugs work by inhibiting the sodium-glucose cotransporter-2 in the kidneys, leading to increased urinary glucose excretion and reduced blood glucose levels. Beyond glycemic control, SGLT2 inhibitors have demonstrated significant cardiovascular and renal benefits. For instance, empagliflozin has shown reductions in cardiovascular and all-cause mortality, while canagliflozin has been associated with lower risks of death-censored graft failure and doubling of serum creatinine in kidney transplant recipients. These benefits make SGLT2 inhibitors a valuable option for patients with Type 2 Diabetes, especially those with cardiovascular or kidney comorbidities.

What other types of research exist?

Promising novel alternatives to SGLT2 inhibitors for Type 2 Diabetes patients include GLP-1 receptor agonists such as semaglutide and liraglutide, which have demonstrated significant efficacy in glycemic control and cardiovascular benefits. Additionally, DPP-4 inhibitors like sitagliptin and linagliptin are viable options, especially for patients with renal impairment. Emerging therapies such as dual GIP/GLP-1 receptor agonists and novel insulin delivery systems are also being explored for their potential benefits.

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SGLT2 Inhibitor

SGLT2 Inhibitors for Heart Failure

Q: What is the mechanism of action of this treatment?

Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors, such as canagliflozin, dapagliflozin, and empagliflozin, work by blocking the reabsorption of glucose in the kidneys, leading to increased glucose excretion in the urine. This helps lower blood glucose levels and can also lead to weight loss and reduced blood pressure. Additionally, SGLT2 inhibitors can increase plasma ketone concentrations, which may provide an alternative energy source for the body. This mechanism is particularly beneficial for Type 2 Diabetes patients as it not only improves glycemic control but also offers cardiovascular and renal protective effects. Other common treatments include Metformin, which decreases hepatic glucose production and improves insulin sensitivity, and GLP-1 receptor agonists, which enhance insulin secretion and inhibit glucagon release. These treatments are crucial for managing blood sugar levels, reducing the risk of diabetes-related complications, and improving overall patient outcomes.

Phase < 1

Recruiting

Led By Carolina Solis-Herrera, MD

Research Sponsored by The University of Texas Health Science Center at San Antonio

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age 18-80 years

Class II-III New York Heart Association (NYHA) heart failure and reduced ejection fraction (EF) <50%

Must not have

Subjects treated with an SGLT2 inhibitor, a glucagon-like peptide-1 receptor agonist (GLP-1 RA) or pioglitazone

Physical disability preventing safe performance of the exercise protocol.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline to 3 months

Summary

This trial uses empagliflozin to help people with Type 2 Diabetes and Heart Failure. The medication increases blood ketone levels, which may improve muscle and heart function, exercise capacity, and overall well-being. Empagliflozin has been shown to reduce cardiovascular death and hospitalization for heart failure in patients with type 2 diabetes.

Who is the study for?

This trial is for adults aged 18-80 with Type 2 Diabetes and moderate heart failure (NYHA Class II-III) who have a reduced heart function (EF <50%). They should have a stable weight, controlled blood pressure, and not be on certain diabetes or heart failure medications. People with very high resting heart rates, extreme hypertension, low oxygen levels at rest, or physical disabilities that prevent exercise are excluded.

What is being tested?

The study is testing the effects of Empagliflozin (a drug for diabetes that also affects fat metabolism) against a placebo in improving muscle energy use, exercise capacity, and patient-reported outcomes in those with both Type 2 Diabetes and heart failure.

What are the potential side effects?

Empagliflozin may cause urinary tract infections, dehydration leading to low blood pressure, ketoacidosis (high acid levels in the blood), genital yeast infections in females and males. It can also affect kidney function.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I am between 18 and 80 years old.

Select...

I have moderate to severe heart failure with an ejection fraction below 50%.

Select...

I have Type 2 Diabetes.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I am currently taking medication for diabetes that includes SGLT2 inhibitors, GLP-1 receptor agonists, or pioglitazone.

Select...

I have a physical disability that makes it unsafe for me to do certain exercises.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline to 3 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline to 3 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline to 3 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

ATPmax production

Change in Adenosine Triphosphate (ATP)

Change in Inorganic Phosphate

+2 more

Secondary study objectives

6 minute walk test

Acetoacetate concentrations

Cardiopulmonary Function

+2 more

Side effects data

From 2024 Phase 4 trial • 72 Patients • NCT03193684

Vaginal yeast infection

100%

80%

60%

40%

20%

Study treatment Arm

Treatment

Control

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Empagliflozin GroupExperimental Treatment1 Intervention

Subjects will be randomized 2:1 to receive empagliflozin, 25mg/day for 3 months

Group II: Placebo groupPlacebo Group1 Intervention

Subjects will be randomized to receive the empagliflozin placebo for 3 months

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Empagliflozin 25 MG

2019

Completed Phase 4

~710

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors, such as canagliflozin, dapagliflozin, and empagliflozin, work by blocking the reabsorption of glucose in the kidneys, leading to increased glucose excretion in the urine. This helps lower blood glucose levels and can also lead to weight loss and reduced blood pressure. Additionally, SGLT2 inhibitors can increase plasma ketone concentrations, which may provide an alternative energy source for the body. This mechanism is particularly beneficial for Type 2 Diabetes patients as it not only improves glycemic control but also offers cardiovascular and renal protective effects. Other common treatments include Metformin, which decreases hepatic glucose production and improves insulin sensitivity, and GLP-1 receptor agonists, which enhance insulin secretion and inhibit glucagon release. These treatments are crucial for managing blood sugar levels, reducing the risk of diabetes-related complications, and improving overall patient outcomes.

Evaluation of the safety of sodium-glucose co-transporter-2 inhibitors for treating patients with type 1 diabetes.