Heart failure used to be treated with a fairly fixed set of medications:

• ACE inhibitors or ARBs
• beta-blockers
• mineralocorticoid receptor antagonists
• diuretics

In 2025, the cardiometabolic toolkit has expanded dramatically.

Two classes originally developed for diabetes, SGLT2 inhibitors and GLP-1 receptor agonists, are now important players in heart failure conversations:

• SGLT2 inhibitors are guideline-recommended to reduce heart failure hospitalizations and slow kidney disease.
• GLP-1 RAs, particularly newer agents like semaglutide and tirzepatide, are showing significant benefits in HFpEF patients with obesity and diabetes by reducing hospitalizations and early death.

This article explains what has changed and what patients should expect when these drugs come up in their heart failure care.

Learn more about the condition here: Heart Failure

SGLT2 Inhibitors From Diabetes Add-On to HF Staple

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, such as empagliflozin and dapagliflozin, were first approved for type 2 diabetes. Over time, large clinical trials showed they:

• reduce hospitalization for heart failure
• slow progression of chronic kidney disease (CKD)
• improve outcomes even without diabetes (in people with heart failure or CKD)

As a result:
SGLT2 inhibitors are now strongly recommended in major guidelines for patients with heart failure with reduced ejection fraction (HFrEF) and often for HFpEF where appropriate.

For patients, this can look like:

• adding a once-daily pill even if blood sugar is “fine,”
• watching for mild diuretic-like effects (more urination),
• and needing periodic monitoring of kidney function and electrolytes.

GLP-1 Receptor Agonists From Diabetes and Weight Loss to HFpEF

GLP-1 receptor agonists (e.g., semaglutide, tirzepatide) are well known now for:

• improving blood sugar control
• causing substantial weight loss
• reducing certain atherosclerotic cardiovascular events (heart attack, stroke) in high-risk diabetes patients

More recently:
Large studies and real-world analyses presented at cardiology conferences and published in leading journals have shown that GLP-1 agonists significantly reduce hospitalization and early death in heart failure patients with obesity and diabetes, particularly HFpEF.

For example:
A 2025 analysis of over 90,000 patients with HFpEF, obesity, and type 2 diabetes found that semaglutide reduced serious outcomes by ~42%, and tirzepatide by up to 58%, compared to placebo.

While not yet formally positioned as universal HF treatments, GLP-1 RAs are increasingly part of the heart failure and obesity conversation, especially for:

• HFpEF + obesity
• HF with significant metabolic risk factors
• patients already using GLP-1s for diabetes or weight loss

Related: Weight Loss

Why HF Treatment Is Now a Cardiometabolic Strategy

Heart failure rarely exists in isolation.

Many patients also have type 2 diabetes, obesity, hypertension, CKD.

Cardiologists and endocrinologists are working more closely to co-manage risk.

The new approach:

• uses SGLT2 inhibitors and GLP-1 RAs not just for glucose or weight, but as part of heart failure risk reduction,
• focuses on lowering hospitalizations, improving exercise tolerance, and enhancing quality of life.

Related: Hypertension

Challenges: Polypharmacy, Side Effects, and Adherence

More effective therapies can also mean more medications:
HF patients may be prescribed 5–8 drugs just for heart failure, plus medications for diabetes, blood pressure, lipids, and more.

Pill burden can become overwhelming, especially for older adults.

Common practical issues:

• dosing complexity (daily pills vs weekly injectables)
• GI side effects with GLP-1 RAs (nausea, diarrhea, etc.)
• low blood pressure or dizziness with aggressive HF regimens (especially when combined with multiple hypertension medications)

Where Compounding May Support Heart Failure Care

Compounding is not about replacing branded HF drugs like SGLT2 inhibitors or GLP-1 RAs, but it can support the rest of the regimen:

• producing liquid or easier-to-swallow formulations of adjunct medications (e.g., certain blood pressure meds in patients with swallowing difficulty)
• creating intermediate doses when patients are highly sensitive and standard strengths cause hypotension or side effects
• removing certain excipients when there are intolerances or allergies

This is especially relevant when patients are already managing heart failure plus metabolic conditions such as obesity and hypertension.
Related: Heart Failure | Hypertension

If GLP-1 therapy is part of the conversation, it’s important to understand the safety and regulatory landscape around compounded versions:
Compounded GLP-1s in 2025 blog

These adjustments must always be:

• guided by the cardiology team or primary care physician
• prepared by a licensed, quality-driven compounding pharmacy

Questions to Ask Your Clinician About HF & These New Drugs

• “Why are you recommending an SGLT2 inhibitor or GLP-1 RA for me?”
• “How will we monitor my kidneys, blood pressure, and weight?”
• “Are there any side effects I should watch closely for?”
• “If my regimen becomes too complex, are there ways to simplify it?”

Final Thoughts New Tools, Same Principle: Treat the Whole Patient

Heart failure care in 2025 is more powerful but also more complex.

SGLT2 inhibitors and GLP-1 RAs:

• offer clear benefits beyond glucose control
• are reshaping risk profiles for many patients
• require thoughtful integration into already busy medication lists

AllMedRx supports this new era not by choosing or prescribing these therapies, but by:

• helping tailor supporting medications to each patient’s realities
• collaborating with clinicians to improve tolerability and access
• keeping safety and transparency at the center of every compounded prescription

To discuss personalized medication support for heart failure patients, clinicians can reach us at:
intake@allmedrx.org