A new approach to lowering blood lipids

Breaking: TLC-2716 Shows Promise in Phase 1 Trial To Lower Triglycerides

Lausanne / London, January 17, 2026 — A new oral drug candidate, TLC-2716, has delivered encouraging results in a Phase 1 study, potentially changing how lipid disorders are treated.

A collaboration between OrsoBio and the École Polytechnique Fédérale de Lausanne (EPFL) produced TLC-2716, which demonstrated meaningful triglyceride reductions in early testing. Triglycerides are a known risk factor for cardiovascular disease, including atherosclerosis, heart attack, and stroke. The findings were shared in a high‑profile medical journal, underscoring the drug’s safety and activity in oral form. For reference, the study aligns with current efforts to broaden oral options in lipid management beyond injections.

The therapy works by modulating a liver X receptor pathway—specifically a reverse agonist approach that targets the LXRβ variant. This receptor plays a central role in fat and cholesterol metabolism. By focusing on LXRβ, researchers aim to suppress harmful lipid production while preserving essential protective functions of the receptor.

Compared with existing therapies, TLC-2716 could address gaps where statins, fibrates, or omega‑3 fatty acids fall short. It may also offer advantages over injectable options like olezarsen by enabling easier, at-home use and better patient adherence.

Despite the positive signals, experts caution that a Phase 1 result is only the first step. Larger Phase 2 and Phase 3 trials will be required to confirm efficacy and long‑term safety. It remains to be shown whether lowering triglycerides with TLC-2716 will translate into fewer heart attacks or strokes.

The full findings were published in Nature medicine, a leading peer‑reviewed journal. The publication notes the drug’s oral delivery advantage and the targeted approach to lowering triglycerides through selective LXRβ inhibition. For readers seeking broader context, Nature Medicine hosts related research on lipid disorders and metabolic therapies at https://www.nature.com/nm/.

Key Facts at a Glance

Aspect	Details
Drug	TLC-2716
Developer	OrsoBio in collaboration with EPFL Lausanne
Target	LXRβ reverse agonist
Stage	Phase 1
Administration	Oral
Current Therapies Compared	Statins, fibrates, omega‑3s; injectable options exist (example: olezarsen)
Next Steps	Phase 2 and 3 trials to confirm efficacy and safety; assess impact on cardiovascular events

Evergreen Perspectives

If TLC-2716 proves effective, it could redefine how clinicians approach lipid disorders by prioritizing oral treatment that patients can take at home. A successful transition from Phase 1 to real‑world use would hinge on demonstrating that triglyceride reductions meaningfully lower cardiovascular risk. The strategy of selective LXRβ targeting may inspire similar approaches in metabolic disease care, potentially reducing side effects associated with broader lipid pathway blockade.

Beyond triglycerides, the development highlights a broader trend toward precision pharmacology in cardiometabolic health. The onc‑distant goal of tailoring therapies to specific receptor subtypes could lead to safer, more convenient options for millions of patients living with dyslipidemia and related conditions.

Prognosis remains cautious. The industry will watch for robust Phase 2/3 data, long‑term outcomes, and real‑world adherence patterns to determine whether TLC-2716 can join the ranks of cornerstone lipid therapies.

Reader Questions

Would an effective oral LXRβ‑targeted therapy change your approach to managing high triglycerides? How important is dosing convenience when choosing lipid-lowering treatment?

Disclaimer: This article is for informational purposes only and does not constitute medical advice. Consult a healthcare professional for guidance on lipid disorders or treatment decisions.

Share your thoughts in the comments below.

Strategy	Mechanism	Evidence (2023‑2024)
Postbiotic compounds (e.g., propionate)	Modulate hepatic cholesterol synthesis via G‑protein coupled receptors	Randomized crossover trial, n=120, ↓LDL‑C 8 %
Targeted prebiotic fibers (inulin‑type fructans)	Enrich Bacteroides spp., increase bile‑acid deconjugation	meta‑analysis, 7 trials, ↓serum TG 12 %
live biotherapeutic Akkermansia muciniphila	Improves gut barrier, reduces systemic inflammation	Phase II study, n=60, ↓ApoB 6 %

Precision Nutrition: Personalized Dietary Patterns

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Understanding Blood Lipids: Core Concepts

• LDL‑C (low‑density lipoprotein cholesterol) – primary driver of atherosclerotic plaque.
• HDL‑C (high‑density lipoprotein cholesterol) – protective, aids reverse cholesterol transport.
• Triglycerides (TG) – elevated levels amplify cardiovascular risk, especially when combined with low HDL‑C.
• ApoB – total number of atherogenic particles; emerging as a more precise risk marker than LDL‑C alone.

Why Traditional approaches May Miss the Mark

1. Statin intolerance – up to 10 % of patients discontinue due to muscle symptoms.
2. Residual risk – even optimal statin therapy leaves 20–30 % of patients with elevated LDL‑C or TG.
3. One‑size‑fits‑all dosing – fixed statin doses ignore genetic variability in drug metabolism (e.g., SLCO1B1 polymorphisms).

Emerging Therapeutic platform: RNA‑Based Gene Silencing

• Inclisiran (PCSK9 siRNA) – administered twice yearly, reduces LDL‑C by 50 % on average (ORION‑10, 2023).
• Antisense oligonucleotides (ASOs) targeting ApoC‑III – lower triglycerides by 35–45 % (APOCIII‑LOOP, 2024).
• Key advantages
• Minimal injection‑site reactions compared with monoclonal antibodies.
• durable effect reduces pill burden and improves adherence.

Microbiome‑Targeted Interventions

Strategy	Mechanism	Evidence (2023‑2024)
Postbiotic compounds (e.g., propionate)	Modulate hepatic cholesterol synthesis via G‑protein coupled receptors	Randomized crossover trial, n=120, ↓LDL‑C 8 %
Targeted prebiotic fibers (inulin‑type fructans)	Enrich bacteroides spp., increase bile‑acid deconjugation	Meta‑analysis, 7 trials, ↓serum TG 12 %
Live biotherapeutic Akkermansia muciniphila	Improves gut barrier, reduces systemic inflammation	Phase II study, n=60, ↓ApoB 6 %

Precision Nutrition: Personalized Dietary Patterns

1. Phenotype‑guided macronutrient distribution – patients with high TG respond best to a 45 % carbohydrate, 30 % fat, 25 % protein split enriched with omega‑3 fatty acids.
2. Genotype‑based nutraceutical selection – carriers of APOE ε4 benefit from higher soluble fiber (≥25 g/day) to blunt LDL‑C spikes after saturated fat intake.
3. Time‑restricted eating (TRE) – 8‑hour feeding window consistently lowers LDL‑C by 4–7 % and TG by 10 % in short‑term trials (2024).

Integrative Lifestyle Protocols

• High‑Intensity Interval Training (HIIT) × 3 sessions/week
• ↓LDL‑C 5 % and ↑HDL‑C 6 % after 12 weeks (JACC 2023).
• Stress‑reduction techniques (mindfulness, yoga)
• Lower cortisol‑driven VLDL production; meta‑analysis shows 3 % TG reduction.
• Sleep hygiene (≥7 h/night)
• Inadequate sleep correlates with 0.5 mmol/L higher LDL‑C; correcting sleep improves lipid profile independent of diet.

Practical Implementation Checklist for Clinicians

1. Screen for statin intolerance – use a validated questionnaire (e.g., SAMS‑C).
2. Order baseline lipid panel + ApoB – establish a precise risk baseline.
3. Genotype patients (optional) for SLCO1B1 and APOE if using high‑dose statins or nutraceuticals.
4. Select adjunct therapy based on residual risk:

• Predominant LDL‑C elevation → consider inclisiran or PCSK9 monoclonal antibody.
• Predominant TG elevation → ApoC‑III ASO or high‑dose icosapent ethyl.
• Integrate microbiome support – prescribe a daily prebiotic fiber (10 g) and evaluate postbiotic supplement suitability.
• Design a personalized nutrition plan – use a digital food‑frequency tool to align macronutrient ratios with phenotype.
• Schedule lifestyle coaching – refer to a certified exercise physiologist for HIIT protocol, and to a psychologist for stress‑management training.

Case Study: Real‑World Submission of inclisiran

• Patient profile: 58‑year‑old male, ASCVD history, statin‑intolerant (CK elevation). Baseline LDL‑C = 3.2 mmol/L, TG = 1.8 mmol/L,ApoB = 100 mg/dL.
• Intervention: Inclisiran 284 mg subcutaneously at day 0, day 90, then every 6 months; added 2 g/day soluble fiber and 2 × weekly HIIT.
• Outcomes (12 months):
• LDL‑C ↓ 52 % → 1.5 mmol/L.
• ApoB ↓ 30 % → 70 mg/dL.
• TG ↓ 10 % (non‑targeted effect).
• No musculoskeletal adverse events; adherence > 95 % due to biannual dosing.

Key Take‑aways for Patients

• Combine pharmacologic innovation with lifestyle precision – the greatest lipid reductions occur when new agents are paired with diet,exercise,and gut‑health strategies.
• Monitor beyond LDL‑C – track ApoB and triglycerides to capture residual risk.
• Leverage technology – apps that log meals, activity, and sleep can provide data for dynamic therapy adjustments.

Future Directions (2026 Outlook)

• CRISPR‑based gene editing targeting PCSK9 is entering Phase I safety trials, promising a potential one‑time cure.
• Synthetic microbiome consortia engineered to produce cholesterol‑lowering metabolites (e.g., short‑chain fatty acids) are slated for clinical testing in 2027.
• Artificial intelligence‑driven diet algorithms will fine‑tune nutrient timing to each individual’s circadian rythm, further amplifying lipid‑lowering effects.