Internal Medicine Updates

First-ever Cardiovascular-Kidney-Metabolic (CKM) Syndrome guideline

• What: the first multisociety (AHA/ACC/ADA/ASN) guideline on CKM syndrome — the interconnected web of obesity, type 2 diabetes, CKD, and cardiovascular disease (published June 2026).
• Key moves: formal CKM staging (Stages 0–4) across the life course; risk quantified with the PREVENT equations (10- and 30-year); eGFR + UACR to characterize kidney disease; SGLT2 inhibitors, GLP-1–based therapy, and finerenone positioned by stage; obesity reframed as a central, modifiable driver.
• Why it matters: gives internists a common cross-specialty language and a prevention-first, coordinated-care model; replaces the 2013 obesity guideline.

Source: Circulation 2026 (PubMed)

2026 ACC/AHA Dyslipidemia guideline — LDL-C targets return

• First major US cholesterol-guideline update since 2018; retitled from "blood cholesterol" to dyslipidemia to capture triglyceride-rich remnants and lipoprotein(a).
• Restores explicit LDL-C / non-HDL-C treatment goals; recommends at least one lifetime Lp(a) measurement; uses PREVENT for risk; PCSK9 monoclonals no longer require a prior ezetimibe trial.

Source: JACC 2026 (PubMed) · AHA science news

2025 AHA/ACC Hypertension guideline — lower targets, PREVENT

Sets lower blood-pressure goals, replaces the Pooled Cohort Equations with the PREVENT equations for risk, and recommends pharmacotherapy at ≥130/80 mmHg for patients with CVD, diabetes, CKD, or elevated risk. Reassess current patients against the new thresholds.

Source: JACC 2025 (PubMed)

VESALIUS-CV — PCSK9 inhibition for primary prevention

In high-risk patients with established atherosclerosis or diabetes but no prior MI or stroke, evolocumab reduced major cardiovascular events — the first demonstration that PCSK9 inhibition lowers events in primary prevention, not just secondary. Expect pressure to escalate lipid-lowering earlier in selected high-risk patients (pending cost/coverage).

Source: NEJM 2026 (PubMed)

Oral PCSK9 inhibitor enlicitide (CORALreef)

An oral PCSK9 inhibitor lowered LDL-C to a degree comparable to injectable monoclonal antibodies, with a placebo-like safety profile. A pill could substantially improve access and adherence; cardiovascular-outcomes data are still awaited.

Source: NEJM 2026 (PubMed)

Beta-blockers after MI with preserved EF — you can de-prescribe

• In post-MI patients with preserved LVEF and no heart failure, routine long-term beta-blockade did not reduce events (REBOOT).
• A dedicated discontinuation trial supported safely stopping beta-blockers in stable, low-risk patients without LV dysfunction (SMART-DECISION).
• Bottom line: continue beta-blockers for reduced EF / heart failure; for preserved EF, omission or discontinuation is reasonable via shared decision-making.

Sources: REBOOT, NEJM 2025 (PubMed) · Discontinuation trial, NEJM 2026 (PubMed)

Left atrial appendage closure as first-line in AF — two trials, mixed signal

• CHAMPION-AF: in AF patients eligible for anticoagulation, LAAC was noninferior to a DOAC for efficacy with less non-procedural bleeding.
• CLOSURE-AF: in older, higher-risk patients, LAAC did not meet noninferiority versus physician-directed medical therapy.
• Bottom line: device-first stroke prevention remains a selective, shared-decision choice — not a blanket recommendation.

Sources: CHAMPION-AF, NEJM 2026 (PubMed) · CLOSURE-AF, NEJM 2026 (PubMed)

First multisociety Acute Pulmonary Embolism guideline

A de novo guideline from ten societies introduces "Acute PE Clinical Categories" to standardize severity, disposition (home vs. early discharge vs. admission), and use of advanced therapies. It favors DOACs over VKAs and LMWH over UFH, and builds in structured follow-up for persistent dyspnea after anticoagulation.

Source: JACC 2026 (PubMed)

2026 AHA/ASA Acute Ischemic Stroke early-management guideline

• Endorses alteplase or tenecteplase within the 4.5-hour window; expands endovascular therapy to selected large-core and basilar-artery occlusions up to 24 hours.
• Advises against aggressive post-reperfusion BP lowering and tight glucose control; adds the first pediatric AIS recommendations.

Source: Stroke 2026 (PubMed)

2026 Surviving Sepsis Campaign guideline

Updates the 2021 edition with more granular guidance on early recognition, antibiotic optimization, hemodynamic targets (especially in older adults), and de-resuscitation / fluid removal after initial stabilization. It newly emphasizes structured post-ICU recovery and long-term follow-up for sepsis survivors.

Source: Crit Care Med 2026 (PubMed)

ADA Standards of Care in Diabetes — 2026

• Continuous glucose monitoring positioned at or near diagnosis; automated insulin delivery preferred for insulin users.
• GLP-1–based therapy supported for type 1 diabetes with obesity for the first time; lower systolic BP target for high CV/renal risk; individualized (not maximal) obesity pharmacotherapy dosing.

Source: Diabetes Care 2026 (PubMed) · Standards of Care

Next-generation incretins — an oral GLP-1 and triple agonists

• Orforglipron, an oral non-peptide GLP-1 receptor agonist, advanced through phase 3 (e.g., ACHIEVE-5) — a pill with no food/water timing restrictions could broaden access in primary care.
• Survodutide (glucagon/GLP-1 agonist) produced large phase-3 weight loss in adults with obesity; the GIP/GLP-1/glucagon triple agonist retatrutide reported topline phase-3 obesity results (still investigational).

Sources: Orforglipron (ACHIEVE-5), JAMA 2026 (PubMed) · Survodutide, NEJM 2026 (PubMed)

Semaglutide for MASH (ESSENCE) — a GLP-1 for liver disease

In patients with metabolic dysfunction–associated steatohepatitis and F2–F3 fibrosis, semaglutide 2.4 mg improved MASH resolution and fibrosis versus placebo — supporting a GLP-1 option for non-cirrhotic MASH. Screen at-risk patients (e.g., type 2 diabetes) with FIB-4.

Source: NEJM 2025 (PubMed)

SGLT2 inhibitors benefit all CKD stages (SMART-C meta-analysis)

An individual-patient-data meta-analysis showed SGLT2 inhibitors slowed CKD progression across the range of eGFR and albuminuria — including low-grade albuminuria and advanced CKD. Consider an SGLT2 inhibitor for nearly all eligible CKD patients.

Source: JAMA 2026 (PubMed)

FIND-CKD — finerenone in non-diabetic CKD

In adults with non-diabetic CKD already on maximally tolerated RAS blockade, finerenone slowed eGFR decline — extending the nonsteroidal MRA story beyond diabetic kidney disease and pointing toward a RAS-inhibitor + SGLT2i + finerenone foundation for proteinuric CKD.

Source: NEJM 2026 (PubMed)

Biologics enter COPD — dupilumab and mepolizumab

In COPD with type 2 inflammation (blood eosinophils ≥300) on triple therapy, dupilumab (pooled BOREAS/NOTUS) and mepolizumab (MATINEE) reduced exacerbations — now recognized add-on options in GOLD 2026. Check blood eosinophils in exacerbation-prone patients.

Sources: Dupilumab pooled, Lancet Respir Med 2025 (PubMed) · Mepolizumab (MATINEE), NEJM 2025 (PubMed)

DESTINY-Breast09 — a new first-line standard for HER2+ breast cancer

Trastuzumab deruxtecan (T-DXd) plus pertuzumab improved progression-free survival versus the taxane-based standard as first-line therapy for HER2-positive metastatic breast cancer. Relevant to internists for awareness, referral, and survivorship; monitor for interstitial lung disease / pneumonitis.

Source: NEJM 2026 (PubMed)

ACP breast cancer screening guidance — and the conflict it creates

• ACP guidance: biennial mammography for average-risk women 50–74; shared decision-making (not routine screening) for ages 40–49.
• Do not use clinical breast exam to screen; discuss discontinuation at ≥75 or limited life expectancy.

Source: Annals of Internal Medicine 2026 (PubMed)