Metabolic health: metabolic syndrome, prediabetes, fatty liver and heart risk
Metabolic health has no single clinical definition, so doctors use metabolic syndrome as the yardstick: three or more of five markers, namely waist size, triglycerides, HDL cholesterol, blood pressure and fasting glucose (AHA/NHLBI). Treatment starts with 7% to 10% weight loss. Wegovy is now approved for heart-risk reduction and for MASH fatty liver.
What it is
"Metabolic health" is a popular phrase, not a diagnosis. The closest clinical measure is metabolic syndrome, which the AHA and NHLBI define as any three of these five (AHA/NHLBI scientific statement, 2005):
- Waist of 40 inches (102 cm) or more in men, 35 inches (89 cm) or more in women
- Triglycerides of 150 mg/dL or more, or on treatment
- HDL cholesterol under 40 mg/dL in men or under 50 mg/dL in women, or on treatment
- Blood pressure of 130/85 mmHg or more, or on treatment
- Fasting glucose of 100 mg/dL or more, or on treatment
Two related conditions sit under the same umbrella. Prediabetes is an A1C of 5.7% to 6.4%, fasting glucose of 100 to 125 mg/dL, or a 2-hour glucose of 140 to 199 mg/dL (ADA Standards of Care 2026). MASLD is fat in the liver not caused by heavy drinking; when inflammation and damage are present it is called MASH (NIDDK).
Why it matters
These problems are widespread and usually silent. About 1 in 3 US adults has metabolic syndrome (NHLBI). An estimated 97.6 million adults, 38% of the adult population, have prediabetes (CDC National Diabetes Statistics Report). Around 24% of US adults have MASLD and 1.5% to 6.5% have MASH (NIDDK).
Each one raises the odds of type 2 diabetes, heart attack and stroke. MASH can progress to scarring of the liver (fibrosis) and cirrhosis. None of them reliably causes symptoms early, so they are found through a waist measurement and routine blood tests.
Treatment options
| Option | What it is | Evidence | Best for |
|---|---|---|---|
| Lifestyle-based weight loss | A daily deficit of 500 to 1,000 calories, at least 30 minutes of moderate exercise on most days, and a diet low in saturated fat, salt and simple sugars. | AHA/NHLBI target 7% to 10% weight loss over 6 to 12 months. In the Diabetes Prevention Program, intensive lifestyle change cut progression to diabetes by 58% (NEJM 2002). | Everyone with metabolic syndrome, prediabetes or MASLD; the first step in each guideline. |
| Metformin for prediabetes | An inexpensive oral glucose-lowering drug sometimes used off-label to delay diabetes in high-risk adults. | Diabetes Prevention Program: metformin reduced progression from prediabetes to type 2 diabetes by 31% versus placebo (NEJM 2002). | Higher-risk prediabetes, especially when lifestyle change alone has not been enough. |
| Semaglutide (Wegovy) for heart risk | Weekly injection or daily pill, labeled to cut heart attack, stroke and cardiovascular death in adults with heart disease plus overweight or obesity. | SELECT: major cardiovascular events in 6.5% on Wegovy vs 8.0% on placebo, hazard ratio 0.80, over a median 41.8 months (Wegovy label). | Adults with prior heart attack, stroke or peripheral artery disease and a BMI of 27 or more, without diabetes. |
| Semaglutide (Wegovy) for MASH | The 2.4 mg weekly injection, approved 15 August 2025 under accelerated approval for noncirrhotic MASH with F2 to F3 fibrosis. | ESSENCE at 72 weeks: steatohepatitis resolved without worse fibrosis in 63% vs 34%; fibrosis improved in 37% vs 22% (Wegovy label). | Adults with biopsy- or test-confirmed MASH and moderate to advanced fibrosis, especially with excess weight. |
| Resmetirom (Rezdiffra) for MASH | A daily thyroid hormone receptor-beta agonist pill from Madrigal, approved 14 March 2024 under accelerated approval for noncirrhotic MASH with F2 to F3 fibrosis. | MAESTRO-NASH at 12 months: MASH resolved in 36% on 100 mg vs 13% on placebo, by the first pathologist's reading (Rezdiffra label). | MASH with fibrosis where weight loss is not the main lever, or alongside it. |
| Blood pressure, cholesterol and glucose medicines | Standard drugs such as statins, ACE inhibitors or ARBs aimed at each individual risk factor. | AHA/NHLBI advise drug treatment of LDL cholesterol, blood pressure and glucose when absolute risk is high enough and lifestyle change has not worked. | People whose individual readings stay above target. |
Approved medications
| Medication | Approved for | Key trial |
|---|---|---|
| Wegovy (semaglutide 2.4 mg) injection: cardiovascular | Cutting the risk of CV death, heart attack or stroke in adults with established heart disease and obesity or overweight (approved 8 Mar 2024) | SELECT (17,604 adults): MACE 6.5% vs 8.0%, hazard ratio 0.80 |
| Wegovy pill (semaglutide 25 mg tablet): cardiovascular | The same cardiovascular risk-reduction indication as the injection, in adults with heart disease and obesity or overweight | Indication listed for the tablets on the Wegovy label (approved 22 Dec 2025); weight data from OASIS 4: −13.6% vs −2.4% at 64 weeks |
| Wegovy (semaglutide 2.4 mg) injection: MASH | Noncirrhotic MASH with moderate to advanced fibrosis (F2–F3) in adults; accelerated approval, 15 Aug 2025 | ESSENCE (800 adults at week 72): MASH resolution 63% vs 34%; fibrosis improvement 37% vs 22% |
| Rezdiffra (resmetirom) tablet | Noncirrhotic MASH with moderate to advanced fibrosis (F2–F3) in adults, with diet and exercise; accelerated approval, 14 Mar 2024 | MAESTRO-NASH (888 adults at month 12): MASH resolution 36% (100 mg) vs 13%; fibrosis improvement 28% vs 15% |
| Zepbound (tirzepatide) | Chronic weight management and OSA only. Its label carries no prediabetes, MASH or cardiovascular indication | SURMOUNT-1 3-year prediabetes cohort: 94% lower risk of progressing to type 2 diabetes vs placebo (NEJM 2024) |
Where GLP-1 medications fit
GLP-1 drugs reach several parts of metabolic health at once because the weight they remove is linked to each risk factor. On the Wegovy label, SELECT participants also lowered waist size by 6.5 cm and triglycerides by about 16% relative to placebo at two years.
The AACE's 2025 algorithm reflects that overlap. It names semaglutide or tirzepatide as preferred for prediabetes and metabolic syndrome, semaglutide for preventing major cardiovascular events, and either drug for MASH (AACE consensus, 2025). AASLD updated its practice guidance on semaglutide for MASH in November 2025.
The approvals are narrower than the guidance, though. Only Wegovy carries cardiovascular and MASH indications; tirzepatide's diabetes-prevention data come from a trial, not a label. A good question for your clinician: "Which of my numbers would change most with weight loss, and which need their own medicine?"
When to see a doctor in person
See a clinician in person for a full metabolic workup if you meet two or more of the five criteria or have a family history of early heart disease. MASH staging may need a liver ultrasound, elastography (FibroScan) or, in some cases, a biopsy. Go to urgent care for chest pain, sudden weakness on one side, or yellowing of the skin and eyes, which can signal liver trouble.
How Temi helps
Temi can renew non-controlled maintenance medicines you already take for these conditions, such as lisinopril for blood pressure or metformin, at $15 a refill review (usetemi.com/prescription/refills, checked 5 Oct 2026). Temi physicians also review requests for compounded semaglutide or tirzepatide for weight; these are non-FDA-approved preparations and carry no MASH or heart indication. Liver staging and heart care need your own doctor.
Frequently asked questions
How do I know if I am metabolically healthy?
Check the five AHA/NHLBI markers: waist circumference, triglycerides, HDL cholesterol, blood pressure and fasting glucose. Meeting three or more thresholds means metabolic syndrome. Having none is a reasonable working definition of metabolic health. You need a tape measure, a blood pressure reading and a fasting blood test; an A1C adds a check for prediabetes.
Can metabolic syndrome be reversed?
Often, at least in part. Because the diagnosis depends on crossing thresholds, bringing waist size, blood pressure, triglycerides, HDL or glucose back under them can remove it. AHA/NHLBI recommend losing 7% to 10% of body weight over 6 to 12 months as the first step. Any medicines for cholesterol or blood pressure should only change after talking with the prescriber.
What medication is approved for fatty liver disease?
Two drugs are FDA-approved for MASH, the inflammatory form of fatty liver, in adults with F2 to F3 fibrosis and no cirrhosis: Rezdiffra (resmetirom), approved 14 March 2024, and Wegovy (semaglutide 2.4 mg), approved 15 August 2025. Both are accelerated approvals that depend on confirmatory outcome trials. Simple fatty liver (MASLD) without inflammation has no approved drug; weight loss is the treatment.
Can GLP-1 drugs prevent type 2 diabetes in people with prediabetes?
Trial data say they can lower the risk, though no GLP-1 drug is labeled for diabetes prevention. In the 3-year prediabetes group of SURMOUNT-1, tirzepatide reduced the risk of developing type 2 diabetes by 94% versus placebo (NEJM 2024). For comparison, the Diabetes Prevention Program found a 58% reduction with intensive lifestyle change and 31% with metformin (NEJM 2002).
Does Wegovy lower the risk of heart attack?
In adults with established heart disease and overweight or obesity, yes. In SELECT, 6.5% of people on Wegovy had a cardiovascular death, heart attack or stroke over a median of about 3.5 years, against 8.0% on placebo, a 20% relative reduction (Wegovy label). People with diabetes were excluded, and the benefit was shown in people who already had heart disease, not in the general population.
What is the difference between MASLD, MASH, NAFLD and NASH?
They are old and new names for the same conditions. NAFLD (nonalcoholic fatty liver disease) is now MASLD, metabolic dysfunction-associated steatotic liver disease. NASH (nonalcoholic steatohepatitis) is now MASH, metabolic dysfunction-associated steatohepatitis. The Wegovy and Rezdiffra labels both note the change. MASH means fat plus inflammation and cell damage, and is the form that can lead to fibrosis.
Sources
- Diagnosis and Management of the Metabolic Syndrome: An AHA/NHLBI Scientific Statement (Circulation, 2005) (checked October 5, 2026)
- AHA and NHLBI Review Diagnosis and Management of the Metabolic Syndrome (American Family Physician, 2006) (checked October 5, 2026)
- Metabolic syndrome, NHLBI (checked October 5, 2026)
- 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes—2026 (ADA) (checked October 5, 2026)
- CDC National Diabetes Statistics Report (checked October 5, 2026)
- Definition and facts of MASLD and MASH, NIDDK (checked October 5, 2026)
- Wegovy (semaglutide) injection and tablets prescribing information, Novo Nordisk (SELECT and ESSENCE in Sections 14.1 and 14.4) (checked October 5, 2026)
- Novo Nordisk: FDA approves Wegovy for MASH with moderate to advanced fibrosis (15 August 2025) (checked October 5, 2026)
- FDA Approves Wegovy for Cardiovascular Risk Reduction in Adults with Known Heart Disease and Overweight or Obesity (DAIC, March 2024) (checked October 5, 2026)
- Rezdiffra (resmetirom) prescribing information, Madrigal Pharmaceuticals (July 2026) (checked October 5, 2026)
- Madrigal announces FDA approval of Rezdiffra (14 March 2024) (checked October 5, 2026)
- Semaglutide therapy for MASH: November 2025 updates to AASLD Practice Guidance (Hepatology) (checked October 5, 2026)
- Tirzepatide for Obesity Treatment and Diabetes Prevention (SURMOUNT-1 3-year, NEJM 2024) (checked October 5, 2026)
- Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin (Diabetes Prevention Program, NEJM 2002) (checked October 5, 2026)
- AACE Consensus Statement: Algorithm for the Evaluation and Treatment of Adults with Obesity/Adiposity-Based Chronic Disease (2025) (checked October 5, 2026)
- Temi: prescription refills ($15 per refill) (checked October 5, 2026)
Compounded semaglutide and compounded tirzepatide are not FDA-approved generics of the brand-name products. A licensed 503A compounding pharmacy prepares each one for a single prescription.
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