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BioVAT (Biological Ventricular Assist Tissue) is a cutting-edge cardiac therapy developed as part of the BioVAT-HF clinical trial. Here's a summary:
What is BioVAT?
BioVAT is an engineered heart muscle patch made from cardiomyocytes and stromal cells derived from induced pluripotent stem cells (iPSCs). It is designed to be surgically implanted onto the surface of a failing heart to physically reinforce and remuscularize the weakened myocardium.
The BioVAT-HF Trial
- Sponsor: University Medical Center Göttingen, supported by the German Center for Cardiovascular Research (DZHK) and Repairon GmbH
- Design: Phase I/II, open-label, non-randomized, multi-center adaptive trial
- Target patients: Advanced heart failure with reduced ejection fraction (HFrEF; EF ≤35%), NYHA class III/IV, despite optimal medical therapy
Hypothesis
Implanting BioVAT patches results in sustainable remuscularization - thickening the heart wall and improving pumping function in end-stage heart failure.
Primary Endpoints
- Target heart wall thickness (HWT) and thickening fraction (HWTF) - measures of implant functionality
- Hospitalization for heart failure
May 2026 NEJM Results
A study published in the New England Journal of Medicine (May 27, 2026) reported that patients who received BioVAT patches showed:
- Heart walls that thickened and re-muscularized
- Improved pumping ability
- Modest improvements in quality of life
The patch is conceived as a bridge to transplant or LVAD implantation for end-stage heart failure patients, given the long wait times for donor hearts.
Surgical Feasibility
A two-center first-in-human surgical experience report (published in JHLT) concluded that EHM implantation as BioVAT is feasible and safe, with clinical testing continuing.
This is a significant step in regenerative cardiology - the idea of using a living muscle patch to biologically augment a failing heart, rather than relying solely on mechanical devices, has long been a goal in the field. Would you like more detail on any aspect - the science, the trial design, or the clinical results?
Filrenone and latest drugs
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Here is a thorough, up-to-date overview of Finerenone and the latest drugs in this class:
Finerenone (Kerendia) - Full Overview
What Is It?
Finerenone is a non-steroidal, selective mineralocorticoid receptor antagonist (nsMRA) - the first of its kind to reach clinical practice. It blocks MR activation by both aldosterone and cortisol in epithelial tissues (kidney) and non-epithelial tissues (heart, blood vessels), reducing fibrosis and inflammation.
- Goodman & Gilman's, block8
How Is It Different From Spironolactone and Eplerenone?
| Feature | Spironolactone | Eplerenone | Finerenone |
|---|---|---|---|
| Structure | Steroidal | Steroidal | Non-steroidal |
| MR selectivity | Low (also binds androgen, progesterone receptors) | Higher | Highest |
| Gynecomastia risk | Yes | Minimal | None |
| Distribution (heart vs kidney) | Favors kidney | Kidney > heart | Equal in heart & kidney |
| t1/2 | ~1.6 h (as canrenone) | ~5 h | ~2-3 h |
| Anti-fibrotic potency | Moderate | Moderate | More potent |
| Hyperkalemia | Significant | Significant | Present but lower |
Key distinction: Finerenone accumulates equally in the heart and kidneys (eplerenone has 3x higher renal concentration), giving it stronger cardiac anti-fibrotic effects.
- Katzung's Pharmacology, 16th Ed.
Mechanism of Action
Finerenone competitively inhibits aldosterone binding to the MR. The MR-finerenone complex cannot induce aldosterone-induced proteins (AIPs), which are responsible for Na+ reabsorption, K+ and H+ secretion. Unlike steroidal MRAs, it does not require tubular lumen access to work.
- Goodman & Gilman's
FDA-Approved Indications (as of July 2025)
1. CKD with Type 2 Diabetes (2021)
Reduces risk of:
- Sustained eGFR decline
- End-stage kidney disease
- Cardiovascular death, non-fatal MI, hospitalization for heart failure
Based on FIDELIO-DKD and FIGARO-DKD trials (>13,000 patients combined):
- 18% relative risk reduction in CKD progression endpoint
- 13% relative risk reduction in CV mortality/morbidity
- National Kidney Foundation Primer, 8e
2. Heart Failure with LVEF ≥40% (July 14, 2025 - NEW)
Reduces risk of:
- Cardiovascular death
- Hospitalization for heart failure
- Urgent heart failure visits
Based on the FINEARTS-HF trial (presented at ESC 2024, published in NEJM):
- 16% relative risk reduction in the composite primary endpoint vs. placebo
- Benefit seen across the ejection fraction spectrum in HFmrEF and HFpEF
- ACC announcement
Dosing
| Indication | Starting Dose | Target Dose |
|---|---|---|
| CKD/T2DM (eGFR ≥60) | 20 mg once daily | 20 mg once daily |
| CKD/T2DM (eGFR 25-60) | 10 mg once daily | Titrate to 20 mg |
| HF with LVEF ≥40% | Per current label | Per FINEARTS-HF protocol |
- Contraindicated if CrCl ≤25 mL/min
- Metabolized by CYP3A4 - monitor with strong inhibitors/inducers
- Goodman & Gilman's
Key Safety Issue: Hyperkalemia
- Most important adverse effect
- Monitor serum K+ before initiation and during treatment
- Hold or reduce dose if K+ rises above threshold
- FDA label (July 2025)
Latest Clinical Trials in 2025-2026
| Trial | Focus | Key Finding |
|---|---|---|
| FINEARTS-HF | HF with LVEF ≥40% | 16% RRR in CV death + HF hospitalization (led to FDA approval) |
| FINEARTS-HF kidney analysis (JACC HF, 2026) | Kidney outcomes in HF | Benefit consistent across spectrum of kidney risk |
| CONFIDENCE (Phase II) | Finerenone + Empagliflozin combination in CKD+T2D | Ongoing - testing combined nsMRA + SGLT2i |
| FINE-ONE | Finerenone in Type 1 diabetes + CKD | Emerging data (ASN Kidney Week 2025) |
The CONFIDENCE trial is particularly exciting - it tests whether combining finerenone with an SGLT2 inhibitor gives additive cardiorenal protection. [PMID: 39916475]
Next-Generation MRAs in the Pipeline
Balcinrenone (AZD-9977) - AstraZeneca
- A newer nsMRA currently in Phase 3 trials (China: Heart Failure; US/EU: CKD)
- Key advantage: animal data shows it reduces proteinuria comparably to eplerenone but with minimal effect on serum potassium - potentially solving the hyperkalemia problem
- Phase 2 data: being studied in combination with dapagliflozin (SGLT2 inhibitor) - MIRACLE trial
- Could expand MRA use to patients currently excluded due to hyperkalemia risk
Zibotentan (ZD4054) - AstraZeneca
- An endothelin-A receptor antagonist (not an MRA, but in the DKD pipeline)
- Originally developed as an anticancer drug; being repurposed for diabetic kidney disease
Clinical Bottom Line
Finerenone represents the fourth pillar of cardiorenal protection in patients with HFrEF, HFpEF/HFmrEF, and CKD with T2DM, alongside:
- RAS inhibitors (ACEi/ARB/ARNI)
- Beta-blockers
- SGLT2 inhibitors
- Finerenone (nsMRA)
Its July 2025 approval for HF with preserved/mildly reduced ejection fraction fills a major gap - HFpEF has historically had very few evidence-based therapies.
Newer OHA with anti obesity drugs
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Here is a comprehensive, fully updated overview of newer oral hypoglycemic agents (OHAs) with anti-obesity properties, including the very latest approvals and pipeline drugs:
Newer OHAs with Anti-Obesity Effects
Overview: Why This Matters
Traditional OHAs (sulfonylureas, insulin) cause weight gain. The newer generation not only controls glucose but actively drives clinically significant weight loss - a paradigm shift in T2DM management. The key classes are:
- GLP-1 receptor agonists
- Dual agonists (GIP+GLP-1)
- SGLT2 inhibitors
- Emerging triple agonists and combination therapies
CLASS 1: GLP-1 Receptor Agonists (GLP-1 RAs)
Mechanism
Mimic endogenous GLP-1 to:
- Stimulate glucose-dependent insulin secretion (no hypoglycemia risk)
- Suppress glucagon
- Slow gastric emptying
- Act on hypothalamic receptors to reduce appetite and food intake
Weight loss is central - not a side effect.
A. Injectable GLP-1 RAs (Approved for Both T2DM and Obesity)
Semaglutide (Ozempic / Wegovy)
- Ozempic (0.5-2 mg SC weekly): T2DM + cardiovascular risk reduction
- Wegovy (2.4 mg SC weekly): Obesity/overweight
- SELECT trial (2024, Nat Med): 15% weight loss sustained over 4 years in non-diabetic obese patients; also showed 20% CV event reduction
- STEP-1 trial: -14.9% mean body weight at 68 weeks [PMID: 38740993]
Liraglutide (Victoza / Saxenda)
- 1.2-1.8 mg SC daily (T2DM); 3 mg SC daily (obesity)
- SCALE trials: weight loss 5-9% vs placebo
B. ORAL GLP-1 RAs - The Game Changers
Oral Semaglutide (Rybelsus / Wegovy pill)
- Rybelsus (3-14 mg daily): approved for T2DM - first oral GLP-1 RA
- Oral Wegovy (25 mg daily): approved for obesity - available in USA since January 2026
- Must be taken fasting (on empty stomach, 30 min before food)
- OASIS trials showed ~15% weight loss
- Phase III STEP UP trial: -17% weight loss with 7.2 mg dose (higher than standard)
- New 25 mg dose data (NEJM, Sep 2025, [PMID: 40934115]): further weight loss in obese adults
⭐ Orforglipron (Foundayo) - Eli Lilly - FDA APPROVED April 1, 2026
- First-in-class oral small-molecule GLP-1 RA - not a peptide
- No food or water restrictions - can be taken any time of day (major advantage over oral semaglutide)
- Once daily tablet
- ATTAIN-1 Phase 3 trial (NEJM, Nov 2025, [PMID: 40960239]): -12.4% body weight at 72 weeks
- ATTAIN-MAINTAIN trial: Successfully maintained weight loss when patients switched FROM injectable GLP-1s (semaglutide/tirzepatide) to orforglipron
- T2DM indication pending (ACHIEVE trial program ongoing - submission expected 2026)
- Approved: Foundayo
CLASS 2: Dual GIP+GLP-1 Receptor Agonist (Twincretin)
Tirzepatide (Mounjaro / Zepbound) - Eli Lilly
- Mounjaro: T2DM (approved 2022)
- Zepbound: Obesity/overweight (approved 2023)
- Activates both GIP and GLP-1 receptors
- Most potent approved anti-obesity drug currently:
- SURMOUNT-1: -20.9% body weight at 72 weeks (15 mg)
- Beats semaglutide head-to-head (SURMOUNT-5)
- Also approved for obstructive sleep apnea (2024) and heart failure with obesity (2024)
- Sabiston Textbook of Surgery
Switching to Tirzepatide from Dulaglutide
A 2025 RCT (Ann Intern Med, [PMID: 40183678]) showed switching to tirzepatide from inadequately controlled lower-dose dulaglutide gave superior glycemic AND weight outcomes.
CLASS 3: SGLT2 Inhibitors
Mechanism
Block sodium-glucose co-transporter 2 in proximal tubule → glucose excretion in urine (glycosuria) → caloric deficit
Weight Loss Effect
- Modest: -2 to -4 kg (less than GLP-1 RAs)
- Initial loss is from fluid/diuresis; sustained loss is from caloric loss (~300 kcal/day of glucosuria)
- Brenner & Rector's Kidney
Key Agents
| Drug | T2DM | Obesity | CV Benefit | Renal Benefit |
|---|---|---|---|---|
| Empagliflozin (Jardiance) | Yes | Off-label | Yes (EMPA-REG) | Yes |
| Dapagliflozin (Farxiga) | Yes | Off-label | Yes | Yes |
| Canagliflozin (Invokana) | Yes | Off-label | Yes | Yes |
SGLT2 inhibitors are now combined with GLP-1 RAs (e.g., CONFIDENCE trial: finerenone + empagliflozin for CKD+T2DM) for additive cardiorenal and weight effects.
PIPELINE: Next-Generation Drugs (2025-2027)
⭐ Retatrutide (LY3437943) - Eli Lilly - Triple Agonist
- Acts on GLP-1 + GIP + Glucagon receptors simultaneously
- Most potent weight loss compound ever tested in Phase 3:
- TRIUMPH-4 (Dec 2025): -28.7% body weight at 68 weeks (12 mg dose) = ~71 lbs average
- TRIUMPH-1 (May 2026): -28.3% body weight
- Also: 75.8% reduction in osteoarthritis pain, 20% LDL reduction, 72% reversal of prediabetes
- Injectable (once weekly SC)
- Not yet FDA approved (as of June 2026); NDA submission expected 2026, approval possibly 2027
CagriSema (Cagrilintide + Semaglutide) - Novo Nordisk
- Combines GLP-1 agonist (semaglutide) + amylin analogue (cagrilintide)
- Phase 3: -20% body weight at ~68 weeks
- FDA NDA filed December 2025
- Once-weekly injection
Amycretin - Novo Nordisk
- First-in-class GLP-1 + amylin receptor agonist in a single molecule
- Oral pill and injectable formulations
- Phase 1 results (Lancet, July 2025, [PMID: 40550229]): promising safety/PK profile
- Phase 3 starting early 2026
Survodutide (BI 456906) - Boehringer Ingelheim
- GLP-1 + Glucagon dual agonist
- Strong data in MASH (metabolic-associated steatohepatitis) + weight loss
- Phase 3 ongoing
Bimagrumab + Semaglutide
- Bimagrumab is an anti-activin receptor IIB antibody (preserves/increases muscle mass while losing fat)
- Combination with semaglutide: Phase 2 showed superior fat loss while preserving lean mass (Nat Med, 2026)
- Addresses the key concern about muscle loss with GLP-1s
Weight Loss Comparison Table
| Drug | Class | Route | Mean Weight Loss | Status |
|---|---|---|---|---|
| Orforglipron 36 mg | GLP-1 RA | Oral daily | -12.4% (~27 lbs) | ✅ FDA Approved April 2026 |
| Oral semaglutide 25 mg | GLP-1 RA | Oral daily | ~-15-17% | ✅ Approved Jan 2026 |
| Semaglutide 2.4 mg | GLP-1 RA | SC weekly | -14.9% (~33 lbs) | ✅ Approved |
| Tirzepatide 15 mg | GIP+GLP-1 | SC weekly | -20.9% (~50 lbs) | ✅ Approved |
| CagriSema | GLP-1+Amylin | SC weekly | -20% | NDA filed Dec 2025 |
| Retatrutide 12 mg | GLP-1+GIP+Glucagon | SC weekly | -28.7% (~71 lbs) | Phase 3 (2026) |
CONFIDENCE Trial: The Combination Era
The CONFIDENCE trial (Phase II, [PMID: 39916475]) is testing finerenone (nsMRA) + empagliflozin (SGLT2i) in CKD+T2DM - the first major trial of two newer cardiorenal protective drugs together.
Key Clinical Points
- GLP-1 RAs and dual agonists are now the preferred OHAs for T2DM patients with obesity, as per ADA/ESC guidelines
- No hypoglycemia with GLP-1 RAs or SGLT2i (unlike sulfonylureas/insulin)
- SGLT2i add modest weight loss + strong cardiorenal protection
- Oral options (oral semaglutide, orforglipron) are expanding access for injection-averse patients
- Weight loss with GLP-1 RAs is partly maintained after stopping but regain occurs - raising the concept of lifetime therapy
- Muscle mass preservation is an emerging concern - driving interest in combinations like bimagrumab+semaglutide
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