Protocols by Charles Sieg

The research frontier

Research frontier: heart disease and diabetes

One-time gene editing, Lp(a) drugs, new LDL and blood pressure drugs, and the work closest to curing or remitting diabetes, with what each result does and does not prove as of November 2026.

Overall evidence Early34 sourcesReviewed November 5, 2026

Most of this is first-in-human, phase 1, or phase 2 work that moves lab numbers; none of the new heart drugs here has yet shown fewer heart attacks, and no result here is a proven cure.

The short version

  • A single infusion of gene editing has cut LDL cholesterol by up to 62% in 35 people (VERVE-102) and ANGPTL3 protein by a mean 79.7% at one dose in 15 people (CTX310). These are small early trials, and nobody knows yet whether the edits prevent heart attacks or what they do over decades1,2.
  • The Lp(a) field just took a hit. Pelacarsen lowered Lp(a) in a trial of 8,323 patients and still missed its primary endpoint, according to a September 4, 2026 Novartis press release that has not been peer reviewed3. The siRNA drugs (lepodisiran, olpasiran, zerlasiran) cut Lp(a) by more than 80% at their higher doses, but their outcome trials are the real test4,5,6.
  • Type 1 diabetes: the closest thing to a cure is cell replacement. Stem-cell islets got 10 of 12 people off insulin at one year, but everyone took immunosuppressive drugs7. Gene-edited islets that hide from the immune system, and islets grown from a patient's own reprogrammed cells, are each one-person results8,9.
  • Type 2 diabetes: remission is real, it is not a cure, and it follows weight loss. In the DiRECT trial 36% of the diet group were in remission at 2 years, and at 5 years 13% of those who kept getting support were in remission10.

What "cure" means on this page

Four different things get called "cure" in headlines, so I use them strictly.

  • Cure: the disease is gone and stays gone without ongoing treatment. Nothing on this page has shown that.
  • Durable remission: the disease markers return to normal off treatment and stay there for a defined period. For type 2 diabetes the standard definition is an HbA1c below 6.5% (48 mmol/mol) measured at least 3 months after stopping glucose-lowering drugs11.
  • Slowing: the disease still arrives, later, or progresses more slowly. Teplizumab is this.
  • Symptom relief or marker control: a number that predicts harm gets better, like LDL or Lp(a), and the harm itself is not yet shown to fall.

Everything below is dated "as of November 2026."

What the research says

One-time gene editing for cholesterol

The logic is simple. LDL cholesterol causes atherosclerotic disease, and the risk grows with how long you are exposed12. People born with loss-of-function variants in ANGPTL3 have lower LDL and triglycerides and a lower lifetime risk of the disease2. Editing a liver gene once is an attempt to buy that lifelong effect with one infusion. The everyday side of LDL is on the heart page.

Early CTX310 (CRISPR Therapeutics) uses CRISPR-Cas9 to switch off ANGPTL3 in the liver. In a phase 1 trial of 15 adults already on the most lipid-lowering therapy they could tolerate, ANGPTL3 fell a mean 79.7% at 0.7 mg/kg and 73.2% at 0.8 mg/kg. No dose-limiting toxicity occurred, three people had infusion reactions, and one participant died suddenly 179 days after the lowest dose. CRISPR Therapeutics funded the trial2. A 2026 NEJM letter on how long the edit lasts has no abstract, so I take no numbers from it13. Cure? No. This is a lab-marker change in 15 people.

Early VERVE-102 is a base editor aimed at PCSK9. In a phase 1 trial of 35 adults with heterozygous familial hypercholesterolemia or premature coronary disease, one infusion cut PCSK9 by 51% to 88% and LDL cholesterol by 9% to 62% depending on dose, an absolute drop of 78 mg/dL at the top dose. No dose-limiting toxicity occurred, and the drops appeared to hold through follow-up, which was at least a year for 15 participants. The sponsor, Verve Therapeutics, funded it1.

What nobody knows: whether these edits are safe over decades, whether they cut heart attacks, and whether off-target edits matter. Both trials were built to answer safety first.

Lp(a): big drops in the number, one big outcome miss

Lp(a) is a genetically set, LDL-like particle that raises the risk of heart disease and aortic valve stenosis, and the European Atherosclerosis Society recommends measuring it at least once in every adult14. The test itself is on the lab tests page.

Mixed The drugs work on the number, and the one outcome trial reported so far, in a press release only, did not show a benefit for the heart.

  • Lepodisiran (Lilly): in the ALPACA trial of 320 people, the pooled 400 mg dose lowered Lp(a) by 93.9 percentage points more than placebo, averaged over days 60 to 180, and no serious adverse event was judged related to the drug. Lilly funded it4.
  • Olpasiran (Amgen): in a dose-finding trial of 281 patients, placebo-adjusted Lp(a) fell 70.5% to 101.1% across doses at 36 weeks5. The authors say longer and larger trials are needed to learn whether it prevents cardiovascular disease, and as of November 2026 I found no outcome result.
  • Zerlasiran (Silence Therapeutics): in 178 patients, time-averaged Lp(a) fell 81.3% to 85.6% more than placebo over 36 weeks6.
  • Muvalaplin (Lilly), a pill that blocks Lp(a) from forming: Lp(a) fell 47.6% to 85.8% more than placebo over 12 weeks in 233 adults at 10, 60, and 240 mg a day15.
  • Pelacarsen (Novartis, licensed from Ionis): on September 4, 2026, Novartis said in a press release that the phase 3 Lp(a)HORIZON trial of 8,323 patients did not meet its primary endpoint. Pelacarsen lowered Lp(a), but the release says that did not translate into reduced cardiovascular risk in the overall study population, and the full data are to be presented at a medical congress3.

The release gives no effect size. Pelacarsen is an antisense drug, a different class from the siRNAs, so it does not settle their trials, but "lower Lp(a) equals fewer heart attacks" is now an open question. Until the outcome trials report, Lp(a) lowering is marker control, not proven protection.

New drug classes for LDL and blood pressure

Moderate Obicetrapib (a CETP inhibitor, NewAmsterdam Pharma): in the BROADWAY trial of 2,530 high-risk adults already on lipid-lowering therapy, 10 mg daily lowered LDL cholesterol by 29.9% at day 84 versus a 2.7% rise on placebo, with similar adverse events in the two groups. NewAmsterdam funded it16. Status as of November 2026: a July 24, 2026 company press release (not peer reviewed) says Europe's CHMP adopted a positive opinion recommending approval of obicetrapib alone and with ezetimibe, with a European Commission decision expected in the second half of 2026. A CHMP opinion is a recommendation, not an approval. The release mentions no US filing, and the PREVAIL outcomes trial of more than 9,500 patients is still running17. I found no FDA or European Commission decision.

Moderate Enlicitide (Merck), an oral PCSK9 inhibitor: in CORALreef Lipids, 2,909 adults with a past atherosclerotic event or at risk of a first one were randomized 2:1 to enlicitide 20 mg or placebo daily. At week 24, LDL cholesterol was down 57.1% on enlicitide and up 3.0% on placebo. MSD (Merck Sharp & Dohme) funded it18. On July 17, 2026, the FDA announced that it had approved enlicitide as Lipfendra, a once-daily tablet used with diet and exercise to lower LDL cholesterol in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia; it is the first PCSK9 inhibitor taken by mouth19. The approval rests on LDL lowering, and the FDA announcement reports no heart-attack or stroke results.

Why LDL lowering still counts: across 26 statin trials, each 1.0 mmol/L LDL reduction cut major vascular events by 22%20. The newer drugs are betting that the same logic holds when the lowering comes from a different route.

Early Zilebesiran is an injected RNA-interference drug that lowers angiotensinogen. In the KARDIA-2 phase 2 trial, 663 adults with uncontrolled hypertension got a single 600 mg injection or placebo on top of one standard drug, and at 3 months their 24-hour systolic pressure was lower than placebo by 12.1, 9.7, and 4.5 mm Hg depending on the background drug. Hyperkalemia (5.5% versus 1.8%) and acute kidney failure (4.9% versus 1.5%) were more common on zilebesiran, though most episodes were mild and resolved without treatment21. In KARDIA-3, a 2025 Alnylam press release (not peer reviewed) says a single 300 mg dose lowered office systolic pressure 5.0 mm Hg more than placebo at month 3, but the study did not meet its pre-specified definition of statistical significance; Alnylam and its partner Roche planned an outcomes trial of about 11,000 patients22. For scale, each 10 mm Hg drop in systolic pressure cut major cardiovascular events by a fifth (relative risk 0.80) in a meta-analysis of 123 trials23.

Type 1 diabetes: delay, replace, hide

Moderate Teplizumab (slowing, not curing). In a 76-person phase 2 trial of high-risk relatives of people with type 1 diabetes, most of them 18 or younger, one 14-day course delayed diagnosis from a median 24.4 to 48.4 months, and diabetes was diagnosed in 43% versus 72% (hazard ratio 0.41)24. The FDA had already approved Tzield to delay stage 3 disease in people with stage 2, and on June 12, 2026 it granted accelerated approval to delay the decline of insulin production in children 8 through 17 recently diagnosed with stage 3. That approval rests on the drug's effect on C-peptide, a lab marker of the body's own insulin production, and a required postapproval study is checking clinical benefit25. This is slowing. The immune attack is delayed, not ended.

Early Zimislecel (VX-880, Vertex): stem cell-derived islets infused into the liver's portal vein. In a phase 1-2 study, all 14 people with at least 12 months of follow-up had working islet cells, shown by C-peptide in the blood; all 12 given the full dose had no severe hypoglycemia and an HbA1c below 7%, and 10 of 12 (83%) were off insulin at day 365. Two participants died (one of cryptococcal meningitis, one of severe dementia from preexisting cognitive decline), everyone took immunosuppressive drugs, and the analyses were interim and not prespecified. Vertex funded it7. That is insulin independence for 10 of 12 people at one year, bought with ongoing immunosuppression: not a cure, and not remission off treatment either. Status as of November 2026: Vertex's November 2, 2026 earnings press release (not peer reviewed) says zimislecel "is designed for patients with blood types A or A/B only" and that Vertex is focusing on a successor, VX-017, now in a phase 1/2 trial, with pivotal development expected in 2027. The release gives no zimislecel filing date26.

For context, the FDA approved a deceased-donor islet product, Lantidra, in June 2023; in its two single-arm studies, 21 of 30 people did not need insulin for a year or more27. Lantidra and the rest of organ and tissue replacement are covered on the organ replacement page.

Early Hypoimmune islets, no immunosuppression. In one man with long-standing type 1 diabetes, donor islets gene-edited to avoid rejection were placed in his forearm muscle, and he took no immunosuppressive drugs. At 12 weeks there was no immune response against the cells, C-peptide showed stable, glucose-responsive insulin secretion, and four adverse events occurred, none serious or related to the study drug8. A 2026 NEJM letter on the cells' long-term survival has no abstract, so I take no numbers from it28. One person, 12 weeks in the main paper, and the abstract does not say he stopped insulin. A promising idea, nowhere near a treatment.

Early Chemically induced stem-cell islets, made from the patient's own cells. In one patient, reported as the first results of a first-in-human phase 1 trial, islets grown from chemically reprogrammed cells were placed under the anterior rectus sheath of the abdomen. The patient was off insulin from day 75 after the transplant; after month 4, time in the target glucose range stayed above 98% with HbA1c around 5%, and at 1 year the study endpoints were met9. Because the cells are the patient's own, there is no donor tissue to reject, but the abstract does not say whether the patient took immunosuppressive drugs or how the autoimmune attack behind type 1 diabetes was handled. One person, first-in-human.

Type 2 diabetes: remission is real, durability is the problem

Moderate Diet and weight loss. In DiRECT, people with type 2 diabetes of less than 6 years' duration were randomized in UK primary care: 149 to a formula-diet program (825 to 853 kcal a day for 12 to 20 weeks, with diabetes drugs stopped, then food reintroduced with support) and 149 to usual care. At 2 years, 36% of the program group were in remission. At 5 years, 13% (11 of 85) of those who kept getting low-intensity support were in remission, against 5% (5 of 93) of the original controls, and only 26% of those in remission at year 2 were still in remission10. That is durable remission for a minority, and the trial team found that keeping the weight off was the main driver.

Moderate Bariatric surgery. In the STAMPEDE randomized trial of 150 people at one center, 5 years after surgery an HbA1c of 6.0% or less, with or without diabetes drugs, was reached by 29% after gastric bypass and 23% after sleeve gastrectomy versus 5% on intensive medical therapy alone; in the intention-to-treat analysis those differences were not statistically significant. Weight was down 23%, 19%, and 5%. Ethicon Endo-Surgery, among others, funded it29. Because the target allowed diabetes drugs, this is control, not remission. Surgery works for many people, and it is surgery.

Moderate Incretin drugs. In SURMOUNT-2, 938 adults with type 2 diabetes and a BMI of 27 or more lost 12.8% to 14.7% of body weight on tirzepatide 10 or 15 mg weekly versus 3.2% on placebo over 72 weeks; Lilly funded it30. That trial measured weight, not remission, so it shows the lever works, not that remission follows. Retatrutide (Lilly) is still investigational: a July 23, 2026 Lilly press release (not peer reviewed) reports average weight loss of up to 20.8% at 80 weeks in 1,152 adults with type 2 diabetes and obesity or overweight, versus 4.0% on placebo, and says Lilly plans to submit it to the FDA in the first quarter of 202731. The drug has its own page: retatrutide.

Why remission matters for the heart: diabetes roughly doubles coronary heart disease risk in a pooled analysis of 102 prospective studies32. The unanswered question is whether remission restores normal heart risk, and the ADA consensus report says the long-term risks and benefits of remission are not well understood11. The day-to-day side, controlling blood sugar, is on the blood sugar page.

Rhonda Patrick on Lp(a) and GLP-1 drugs

Rhonda Patrick, PhD, has covered both topics in FoundMyFitness Q&A episodes, though her Lp(a) answer predates the siRNA and outcome-trial results above. In Q&A #34 (April 2, 2022) she describes Lp(a) as a cholesterol-carrying particle similar to LDL, linked to heart attack, stroke, and aortic valve stenosis; says genetics largely set the level; says statins generally don't lower it; and points to PCSK9 inhibitors as drugs that do, though they are expensive33. In a clip from Q&A #56 on GLP-1 drugs (May 9, 2024), she walks through the semaglutide and tirzepatide trials, the loss of lean mass that can come with major weight loss, side effects, and the finding that stopping treatment commonly leads to regain34. I'm citing her for background; this is not an endorsement of me or this site.

Cautions

  • Nothing here is medical advice, and no result on this page tells anyone what to take. I'm describing trials, with the doses and regimens the trials used.
  • Retatrutide is not approved in the US as of November 2026, and its figures here come from a company press release, not a peer-reviewed paper31.
  • The Lp(a) results and the ANGPTL3 and PCSK9 editing results are lab-marker results. Outcome trials (fewer heart attacks, fewer deaths) are the ones that count, and the only Lp(a) outcome result I found as of November 2026 was a miss, reported in a company press release3.
  • Cell therapies for type 1 diabetes still need immunosuppressive drugs outside single-patient experiments, and two participants died in the zimislecel study7,8.
  • Dates, approvals, and trial phases move fast. Everything marked "as of November 2026" can change; the sponsor, the FDA, and ClinicalTrials.gov have the current status.

References

  1. Vafai SB, Täubel J, Ashdown T, Patel RS, Diamondali S, Cegla J, et al. In Vivo Base Editing of PCSK9 with VERVE-102 for Hypercholesterolemia. The New England Journal of Medicine. 2026;395(7):648-659.Cohort studyPubMed 42187087 · DOI

    What it found: Phase 1, open-label, single-ascending-dose trial of VERVE-102, an adenine base editor aimed at PCSK9, given as one infusion to 35 adults with heterozygous familial hypercholesterolemia or premature coronary artery disease. PCSK9 fell 51% at 0.3 mg/kg to 88% at 1.0 mg/kg, LDL-C fell 9% to 62% (an absolute drop of 78 mg/dL at the top dose), no dose-limiting toxicity occurred, and 15 participants had at least 1 year of follow-up.

    Limits: Thirty-five people in a safety-first trial funded by Verve Therapeutics, with no heart-attack outcomes and follow-up of about a year for only some of them.

  2. Laffin LJ, Nicholls SJ, Scott RS, Clifton PM, Baker J, Sarraju A, et al. Phase 1 Trial of CRISPR-Cas9 Gene Editing Targeting ANGPTL3. The New England Journal of Medicine. 2025;393(21):2119-2130.Cohort studyPubMed 41211945 · DOI

    What it found: Ascending-dose phase 1 trial of CTX310, a lipid-nanoparticle CRISPR-Cas9 therapy aimed at liver ANGPTL3, given as one infusion to 15 adults with uncontrolled high cholesterol, high triglycerides, or mixed dyslipidemia on maximal therapy. ANGPTL3 fell a mean 79.7% at 0.7 mg/kg and 73.2% at 0.8 mg/kg; no dose-limiting toxicity occurred, three people had infusion reactions, and one participant died suddenly on day 179 after the 0.1 mg/kg dose.

    Limits: Fifteen people in a dose-finding trial funded by CRISPR Therapeutics, with the abstract reporting ANGPTL3 levels and safety rather than LDL, triglycerides, or heart attacks.

  3. Novartis. Novartis announces Lp(a)HORIZON Phase III topline results for pelacarsen in patients with elevated Lp(a) and established cardiovascular disease (CVD). Novartis media release, September 4, 2026.ArticleRead

    What it found: Company press release, not peer-reviewed. The trial of 8,323 patients with elevated Lp(a) and established cardiovascular disease did not meet its primary endpoint (cardiovascular death, nonfatal heart attack, nonfatal stroke, or urgent coronary revascularization requiring hospitalization); pelacarsen lowered Lp(a) but this did not translate into fewer cardiovascular events in the overall population (Lp(a) of 70 mg/dL or higher).

    Limits: A topline statement with no effect sizes, safety data, or dose; full results are promised at an unnamed medical congress.

  4. Nissen SE, Ni W, Shen X, Wang Q, Navar AM, Nicholls SJ, et al. Lepodisiran - A Long-Duration Small Interfering RNA Targeting Lipoprotein(a). The New England Journal of Medicine. 2025;392(17):1673-1683.Randomized trialPubMed 40162643 · DOI

    What it found: ALPACA trial of 320 randomized adults with a median baseline Lp(a) of 253.9 nmol/L. Placebo-adjusted time-averaged Lp(a) change from day 60 to day 180 was -40.8 points at 16 mg, -75.2 at 96 mg, and -93.9 at the pooled 400 mg doses; serious adverse events occurred in 35 participants and none was judged related to treatment.

    Limits: A lab-marker trial funded by Eli Lilly that cannot show fewer heart attacks, which the separate outcomes trial must answer.

  5. O'Donoghue ML, Rosenson RS, Gencer B, López JAG, Lepor NE, Baum SJ, et al. Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease. The New England Journal of Medicine. 2022;387(20):1855-1864.Randomized trialPubMed 36342163 · DOI

    What it found: Dose-finding, double-blind trial of olpasiran in 281 patients with established atherosclerotic disease and Lp(a) above 150 nmol/L. At week 36 the placebo-adjusted Lp(a) change was -70.5% at 10 mg, -97.4% at 75 mg, -101.1% at 225 mg every 12 weeks, and -100.5% at 225 mg every 24 weeks; the most common drug-related events were injection-site reactions.

    Limits: A dose-finding lab-marker trial funded by Amgen, so it shows Lp(a) falls but not that fewer heart attacks follow.

  6. Nissen SE, Wang Q, Nicholls SJ, Navar AM, Ray KK, Schwartz GG, et al. Zerlasiran-A Small-Interfering RNA Targeting Lipoprotein(a): A Phase 2 Randomized Clinical Trial. JAMA. 2024;332(23):1992-2002.Randomized trialPubMed 39556769 · DOI

    What it found: Phase 2 trial of 178 patients with stable atherosclerotic disease and Lp(a) of at least 125 nmol/L. Time-averaged Lp(a) fell 85.6% with 450 mg every 24 weeks, 82.8% with 300 mg every 16 weeks, and 81.3% with 300 mg every 24 weeks versus pooled placebo over 36 weeks; the most common treatment-related effects were injection-site reactions.

    Limits: A 36-week lab-marker trial that cannot show fewer heart attacks.

  7. Reichman TW, Markmann JF, Odorico J, Witkowski P, Fung JJ, Wijkstrom M, et al. Stem Cell-Derived, Fully Differentiated Islets for Type 1 Diabetes. The New England Journal of Medicine. 2025;393(9):858-868.Cohort studyPubMed 40544428 · DOI

    What it found: Phase 1-2 study of zimislecel (VX-880), stem cell-derived islets infused into the portal vein with glucocorticoid-free immunosuppression. Of 14 participants with at least 12 months of follow-up, all had detectable C-peptide; all 12 who got the full dose were free of severe hypoglycemia with HbA1c below 7%, and 10 of 12 (83%) were insulin independent at day 365; two participants died (cryptococcal meningitis, and severe dementia with agitation).

    Limits: A small, interim, non-prespecified analysis funded by Vertex in which participants needed immunosuppressive drugs.

  8. Carlsson PO, Hu X, Scholz H, Ingvast S, Lundgren T, Scholz T, et al. Survival of Transplanted Allogeneic Beta Cells with No Immunosuppression. The New England Journal of Medicine, 2025.ArticlePubMed 40757665 · DOI

    What it found: Case report of one man with long-standing type 1 diabetes given genetically modified (CRISPR-Cas12b and lentiviral) allogeneic donor islet cells in the forearm muscle with no immunosuppressive drugs. At 12 weeks there was no immune response against the cells, C-peptide showed stable glucose-responsive insulin secretion, and there were four adverse events, none serious or related to the study drug.

    Limits: One person followed for 12 weeks in this report, and the abstract does not say whether he stopped insulin.

  9. Wang S, Du Y, Zhang B, Meng G, Liu Z, Liew SY, et al. Transplantation of chemically induced pluripotent stem-cell-derived islets under abdominal anterior rectus sheath in a type 1 diabetes patient. Cell, 2024.ArticlePubMed 39326417 · DOI

    What it found: One-year results from a single patient in a first-in-human phase I trial of autologous chemically induced stem-cell-derived islets placed under the abdominal rectus sheath. The patient became insulin independent 75 days after transplant, time in target range rose from 43.18% to 96.21% by month 4, and HbA1c stayed around 5%; all study endpoints were met at 1 year.

    Limits: One person in a first-in-human report, using the patient's own cells, so it says nothing yet about how common the result is or how long it lasts.

  10. Lean ME, Leslie WS, Barnes AC, Brosnahan N, Thom G, McCombie L, et al. 5-year follow-up of the randomised Diabetes Remission Clinical Trial (DiRECT) of continued support for weight loss maintenance in the UK: an extension study. The Lancet Diabetes & Endocrinology. 2024;12(4):233-246.Randomized trialPubMed 38423026 · DOI

    What it found: Five-year extension of a UK primary-care trial in which 149 people with type 2 diabetes of under 6 years were assigned to a diet-replacement weight program and 149 to usual care; at 2 years 36% of participants in the program were in remission. At 5 years 11 of 85 (13%) extension participants who kept low-intensity support were in remission versus 5 of 93 (5%) original controls, and 26% of those in remission at year 2 remained in remission; the original program group was in remission at 27% of visits versus 4% for controls.

    Limits: The 5-year data come from an extension with a smaller, self-selected group, and remission was tied to keeping the weight off.

  11. Riddle MC, Cefalu WT, Evans PH, Gerstein HC, Nauck MA, Oh WK, et al. Consensus Report: Definition and Interpretation of Remission in Type 2 Diabetes. Diabetes Care. 2021;44(10):2438-2444.Position standPubMed 34462270 · DOI

    What it found: An international expert group convened by the American Diabetes Association proposed "remission" as the term for glucose returning to normal range, with the usual criterion an HbA1c below 6.5% (48 mmol/mol) measured at least 3 months after stopping glucose-lowering drugs, and suggested how to monitor people in remission.

    Limits: A definitions consensus, not a trial, and the abstract says the long-term risks and benefits of remission are unclear.

  12. Ference BA, Ginsberg HN, Graham I, Ray KK, Packard CJ, Bruckert E, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. European Heart Journal. 2017;38(32):2459-2472.Position standPubMed 28444290 · DOI

    What it found: Consensus review of genetic studies, more than 200 prospective cohorts, Mendelian randomization studies, and randomized trials covering more than 2 million participants, over 20 million person-years, and over 150,000 cardiovascular events. It found a consistent, dose-dependent, log-linear link between LDL exposure and cardiovascular risk that grows with the duration of exposure, and concluded that LDL causes atherosclerotic cardiovascular disease.

    Limits: A consensus review of other studies, not a new trial; it rests on the quality of the underlying genetic, cohort, and trial data.

  13. Laffin LJ, Nicholls SJ, Scott RS, Clifton PM, Koops R, Sarraju A, et al. Durability of CRISPR-Cas9 Gene Editing Targeting ANGPTL3 with CTX310. The New England Journal of Medicine, 2026.ArticlePubMed 42663980 · DOI

    What it found: A 2026 NEJM letter from the CTX310 investigators reporting longer follow-up of the one-time ANGPTL3 gene-editing trial; the PubMed record lists it as a letter with no abstract.

    Limits: I could confirm the letter exists but not read its text, so I quote no durability numbers from it.

  14. Kronenberg F, Mora S, Stroes ESG, Ference BA, Arsenault BJ, Berglund L, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. European Heart Journal. 2022;43(39):3925-3946.Position standPubMed 36036785 · DOI

    What it found: European Atherosclerosis Society consensus statement concluding that Lp(a) is a causal, continuous risk factor for cardiovascular disease and aortic valve stenosis across ethnic groups, including at very low LDL cholesterol. It recommends at least one Lp(a) measurement in every adult and early, intensive management of other risk factors when Lp(a) is high.

    Limits: A consensus statement, not a trial; the abstract notes that Lp(a)-specific drugs still need outcome trials to confirm clinical benefit.

  15. Nicholls SJ, Ni W, Rhodes GM, Nissen SE, Navar AM, Michael LF, et al. Oral Muvalaplin for Lowering of Lipoprotein(a): A Randomized Clinical Trial. JAMA. 2025;333(3):222-231.Randomized trialPubMed 39556768 · DOI

    What it found: Phase 2 trial of 233 adults with Lp(a) of at least 175 nmol/L given oral muvalaplin or placebo for 12 weeks. On the intact Lp(a) assay the placebo-adjusted reduction was 47.6% at 10 mg a day, 81.7% at 60 mg, and 85.8% at 240 mg; high-sensitivity CRP did not change and no safety concerns were seen.

    Limits: Twelve weeks, a lab-marker endpoint, and the effect on cardiovascular events is still unstudied.

  16. Nicholls SJ, Nelson AJ, Ditmarsch M, Kastelein JJP, Ballantyne CM, Ray KK, et al. Safety and Efficacy of Obicetrapib in Patients at High Cardiovascular Risk. The New England Journal of Medicine. 2025;393(1):51-61.Randomized trialPubMed 40337982 · DOI

    What it found: BROADWAY trial of 2,530 adults with heterozygous familial hypercholesterolemia or atherosclerotic disease on maximally tolerated lipid-lowering therapy, randomized 2:1 to obicetrapib 10 mg daily or placebo for 365 days. At day 84 LDL-C fell 29.9% with obicetrapib versus a 2.7% rise with placebo, a difference of 32.6 percentage points (95% CI -35.8 to -29.5), and adverse events were similar between groups.

    Limits: A lipid-lowering trial funded by NewAmsterdam Pharma that cannot show fewer heart attacks; the PREVAIL outcomes trial is still running.

  17. NewAmsterdam Pharma; Menarini Group. NewAmsterdam Pharma and Menarini Group Receive Positive CHMP Opinion Recommending Marketing Authorization for Ubeslo (obicetrapib) and Evlarco (obicetrapib/ezetimibe). NewAmsterdam Pharma Form 8-K, Exhibit 99.1 (company press release), July 24, 2026.ArticleRead

    What it found: Company press release filed July 24, 2026: the European CHMP adopted a positive opinion recommending marketing authorization for obicetrapib 10 mg alone and with ezetimibe 10 mg for primary hypercholesterolemia or mixed dyslipidemia, with a European Commission decision expected in the second half of 2026. It mentions no US filing and describes the PREVAIL outcomes trial (more than 9,500 randomized patients, enrollment completed April 2024) as ongoing.

    Limits: A company document that gives no US regulatory status and no PREVAIL readout date; I could not confirm a European Commission decision on a Commission or EMA page.

  18. Navar AM, Mikhailova E, Catapano AL, Banka P, Blom DJ, Cadena A, et al. A Placebo-Controlled Trial of the Oral PCSK9 Inhibitor Enlicitide. The New England Journal of Medicine. 2026;394(6):529-539.Randomized trialPubMed 41879224 · DOI

    What it found: CORALreef Lipids trial in 2,909 adults with a prior atherosclerotic event or at risk for a first one, randomized 2:1 to enlicitide 20 mg or placebo daily for 52 weeks. At week 24 LDL-C fell 57.1% with enlicitide and rose 3.0% with placebo, an adjusted difference of 55.8 percentage points (95% CI -60.9 to -50.7).

    Limits: A lipid endpoint funded by MSD, and the abstract gives no numeric side-effect rates or heart-attack outcomes.

  19. U.S. Food and Drug Administration. FDA Approves First Oral PCSK9 Inhibitor to Lower LDL Cholesterol in Adults with High Cholesterol. U.S. Food and Drug Administration (press announcement), July 17, 2026.Regulatory noticeRead

    What it found: FDA announcement that Lipfendra (enlicitide), a once-daily oral tablet and the first oral PCSK9 inhibitor, approved for Merck Sharp & Dohme LLC, is an adjunct to diet and exercise to lower LDL-C in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia; in two trials of 3,207 adults on maximally tolerated statins, LDL-C fell an average of 56% and 59% versus placebo at week 24, the trials' primary endpoint.

    Limits: The page mentions no cardiovascular outcomes data; it says nothing about whether the drug prevents heart attacks or strokes.

  20. Cholesterol Treatment Trialists' (CTT) Collaboration, Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet (London, England). 2010;376(9753):1670-1681.Meta-analysisPubMed 21067804 · DOI

    What it found: Individual-patient meta-analysis of 26 statin trials (39,612 people in 5 trials of more versus less intensive therapy, 129,526 in 21 trials of statin versus control). Each 1.0 mmol/L LDL reduction cut major vascular events by 22% (RR 0.78, 95% CI 0.76 to 0.80) and all-cause mortality by 10% (RR 0.90), with no effect on cancer incidence (RR 1.00).

    Limits: The abstract reports mortality and cancer outcomes but not muscle or liver side effects, and the trials were mostly in people already at elevated risk.

  21. Desai AS, Karns AD, Badariene J, Aswad A, Neutel JM, Kazi F, et al. Add-On Treatment With Zilebesiran for Inadequately Controlled Hypertension: The KARDIA-2 Randomized Clinical Trial. JAMA. 2025;334(1):46-55.Randomized trialPubMed 40434761 · DOI

    What it found: Phase 2 double-blind trial of 663 adults with uncontrolled hypertension on indapamide, amlodipine, or olmesartan, randomized to a single 600 mg subcutaneous dose of zilebesiran or placebo. At 3 months 24-hour systolic pressure was lower than placebo by 12.1 mm Hg (indapamide), 9.7 (amlodipine), and 4.5 (olmesartan); hyperkalemia was 5.5% versus 1.8% and acute kidney failure 4.9% versus 1.5%.

    Limits: A 3-month blood pressure result with no heart or stroke outcomes, and with more hyperkalemia and kidney events than placebo.

  22. Alnylam Pharmaceuticals; Roche. Alnylam to Advance Zilebesiran into Global Phase 3 Cardiovascular Outcomes Trial. Alnylam press release via BioSpace (company press release, not yet peer-reviewed), August 30, 2025.ArticleRead

    What it found: Company press release: in the KARDIA-3 phase 2 study (Cohort A, 270 patients) the 300 mg dose lowered office systolic pressure a placebo-adjusted 5.0 mm Hg at month 3 (p=0.0431), but the company says the study did not meet its pre-specified definition of statistical significance after multiplicity control. The companies plan the ZENITH outcomes trial of about 11,000 patients in more than 30 countries, expected to start by the end of 2025.

    Limits: A company press release; I did not find whether ZENITH has started, and the 600 mg arm showed no extra benefit.

  23. Ettehad D, Emdin CA, Kiran A, Anderson SG, Callender T, Emberson J, et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet (London, England). 2016;387(10022):957-967.Meta-analysisPubMed 26724178 · DOI

    What it found: Meta-analysis of 123 trials with 613,815 participants. Each 10 mm Hg lower systolic pressure cut major cardiovascular events (RR 0.80, 95% CI 0.77 to 0.83), coronary heart disease (0.83), stroke (0.73), heart failure (0.72), and all-cause mortality (0.87, 0.84 to 0.91).

    Limits: Pools trials of drug treatment, so it shows what lowering pressure with medication does, not what diet or exercise alone would do.

  24. Herold KC, Bundy BN, Long SA, Bluestone JA, DiMeglio LA, Dufort MJ, et al. An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. The New England Journal of Medicine. 2019;381(7):603-613.Randomized trialPubMed 31180194 · DOI

    What it found: Phase 2 double-blind trial of 76 non-diabetic relatives at high risk for type 1 diabetes (44 teplizumab, 32 placebo) given one 14-day course. Median time to diagnosis was 48.4 months with teplizumab versus 24.4 months with placebo, and diabetes was diagnosed in 43% versus 72% (hazard ratio 0.41, 95% CI 0.22 to 0.78).

    Limits: Seventy-six people, mostly children, and the drug delays diagnosis rather than preventing the disease; rash and transient lymphopenia were expected adverse events.

  25. U.S. Food and Drug Administration. FDA Approves New Indication for Tzield (teplizumab) for Certain Pediatric Patients with Recently Diagnosed Stage 3 Type 1 Diabetes. FDA press announcement, June 15, 2026.Regulatory noticeRead

    What it found: FDA announcement dated June 15, 2026 that Tzield (teplizumab) was approved on June 12, 2026, under accelerated approval, to delay the decline of insulin production in pediatric patients aged 8 through 17 recently diagnosed with stage 3 type 1 diabetes, based on a statistically significant effect on C-peptide. It says Tzield was previously approved to delay stage 3 in people with stage 2 disease, and a required postapproval study is ongoing to verify clinical benefit.

    Limits: The page names no trial and gives no patient numbers, and accelerated approval on C-peptide is not proof of clinical benefit.

  26. Vertex Pharmaceuticals. Vertex Reports Third Quarter 2026 Financial Results. Vertex press release (company press release, mirrored on Finviz), November 2, 2026.ArticleRead

    What it found: Company earnings release of November 2, 2026: it says zimislecel is designed only for patients with blood types A or A/B, and that Vertex is focusing on VX-017, an allogeneic stem cell-derived islet therapy designed to work regardless of blood type, now in a phase 1/2 trial with Fast Track designation and pivotal development expected in 2027. It gives no filing date for zimislecel and mentions no pause.

    Limits: A company release read on a mirror site, with no trial data, and the zimislecel status line is brief.

  27. U.S. Food and Drug Administration. FDA Approves First Cellular Therapy to Treat Patients with Type 1 Diabetes. FDA press announcement, June 28, 2023.Regulatory noticeRead

    What it found: FDA announcement that Lantidra, a deceased-donor islet cell therapy infused into the liver portal vein, was approved for adults with type 1 diabetes and repeated severe hypoglycemia despite intensive management. In two single-arm studies of 30 participants, 21 did not need insulin for a year or more, and most had a serious reaction to the procedure or the immunosuppressive drugs.

    Limits: Two non-randomized studies; the islets need immunosuppressive drugs to survive, and some serious reactions forced those drugs to stop, which ended islet function and insulin independence.

  28. Carlsson PO, Hu X, Scholz H, Lundgren T, Ingvast S, Scholz T, et al. Long-Term Survival of Hypoimmune Allogeneic Islets without Immunosuppression. The New England Journal of Medicine, 2026.ArticlePubMed 42430558 · DOI

    What it found: A 2026 NEJM letter from the same group reporting longer follow-up of the hypoimmune islet transplant; the PubMed record lists it as a letter with no abstract.

    Limits: I could confirm the letter exists but not read its text, so I quote no follow-up length or results from it.

  29. Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Aminian A, Brethauer SA, et al. Bariatric Surgery versus Intensive Medical Therapy for Diabetes - 5-Year Outcomes. The New England Journal of Medicine. 2017;376(7):641-651.Randomized trialPubMed 28199805 · DOI

    What it found: STAMPEDE: 150 people with type 2 diabetes and a BMI of 27 to 43 randomized to intensive medical therapy alone or with gastric bypass or sleeve gastrectomy; 134 were analyzed at 5 years. The HbA1c goal of 6.0% or less was met by 5% on medical therapy, 29% after gastric bypass, and 23% after sleeve gastrectomy, with weight down 5%, 23%, and 19%.

    Limits: A small single-center trial funded in part by Ethicon Endo-Surgery, with intention-to-treat comparisons that did not all reach significance.

  30. Garvey WT, Frias JP, Jastreboff AM, le Roux CW, Sattar N, Aizenberg D, et al. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. The Lancet. 2023;402(10402):613-626.Randomized trialPubMed 37385275 · DOI

    What it found: Phase 3 trial of 938 adults with BMI of 27 or higher and type 2 diabetes (HbA1c 7% to 10%) given tirzepatide 10 mg, 15 mg, or placebo once weekly for 72 weeks. Weight fell 12.8% on 10 mg, 14.7% on 15 mg, and 3.2% on placebo; fewer than 5% stopped for adverse events, and two deaths in the 10 mg group were judged unrelated.

    Limits: A weight trial funded by Eli Lilly that did not test remission, and it ran 72 weeks.

  31. Eli Lilly and Company. Lilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1C. Eli Lilly and Company press release (PR Newswire); copy read on BioSpace, July 23, 2026.ArticleRead

    What it found: Company press release, not peer-reviewed: Lilly calls retatrutide an investigational once-weekly triple hormone receptor agonist and says it plans to submit a Biologics License Application to the FDA in Q1 2027. TRIUMPH-2 (1,152 people with type 2 diabetes and obesity or overweight, 80 weeks) reported weight loss of 12.7% to 20.8% versus 4.0% on placebo and A1C changes of -1.4% to -1.6% from a 7.7% baseline versus -0.2%; diarrhea ran 27.4% to 33.6% versus 13.2% on placebo and dysesthesia 4.5% to 7.3% versus 0.7%.

    Limits: A company topline release with the efficacy estimand and no peer review; Lilly's own investor page answered 403 to our checks, so the link goes to the same release as reposted on BioSpace.

  32. Emerging Risk Factors Collaboration, Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet (London, England). 2010;375(9733):2215-2222.Meta-analysisPubMed 20609967 · DOI

    What it found: Collaborative analysis of 102 prospective studies (698,782 people, 52,765 vascular outcomes). Diabetes roughly doubled coronary heart disease risk (HR 2.00, 95% CI 1.83 to 2.19) and raised ischemic stroke risk (2.27); fasting glucose showed no significant link to risk between 3.90 and 5.59 mmol/L but risk rose above that.

    Limits: Observational; it tracks diabetes and glucose as risk markers and cannot separate their effect from related factors like weight and blood pressure.

  33. Patrick R. Q&A #34: Is Dark Chocolate Heart-Healthy—and What Does High Lp(a) Mean for Heart Risk?. FoundMyFitness, April 2, 2022.PodcastListen

    What it found: Rhonda Patrick's Q&A answer on lipoprotein(a): she describes it as an LDL-like particle linked to coronary disease, heart attack, stroke, and aortic valve stenosis, says genetics largely set the level, that statins generally don't lower it well, and that PCSK9 inhibitors lower it but are expensive.

    Limits: A 2022 members-only Q&A that predates the siRNA and outcome-trial results, paraphrased from the episode page.

  34. Patrick R. How GLP-1 Drugs Support Weight Loss and Their Tradeoffs (clip from Q&A #56: Ozempic for Weight Loss, Muscle Loss, Side Effects, & Weight Regain). FoundMyFitness, May 9, 2024.PodcastListen

    What it found: A clip page from Rhonda Patrick's Q&A #56 covering GIP and GLP-1, the semaglutide and tirzepatide weight-loss trials, muscle and lean-mass concerns, side effects, and the point that stopping treatment commonly leads to regain.

    Limits: A clip-page summary dated May 9, 2024, not a peer-reviewed source, and it reviews trials rather than adding data.