Metabolic health

What metabolic health means#

Metabolic health means your body handles fuel well: blood sugar, blood fats, blood pressure, and body fat sit in healthy ranges without medication. When it fails, the same root problem shows up across organs as type 2 diabetes, fatty liver, kidney disease, high blood pressure, and eventually heart attack and stroke.

The analysis of 55,081 adults in national surveys found things getting worse: between 1999 and 2018, the share with optimal body fat fell from 33.8% to 24.0%, and the share with optimal glucose from 59.4% to 36.9%.

The older label for this cluster is metabolic syndrome: three of five risk factors, using cutoffs of a waist over 40 inches (102 cm) for men or 35 inches (88 cm) for women, triglycerides of 150 mg/dL or more, HDL under 40 mg/dL for men or 50 for women, blood pressure of 130/85 or higher, and fasting glucose of 100 mg/dL or higher (NHLBI). These are disease thresholds, not healthy targets; the targets are in Metabolic markers at a glance.

In 2023 the American Heart Association added a broader frame, cardiovascular-kidney-metabolic (CKM) syndrome: excess fat, insulin resistance, kidney damage, and heart disease feed one another, which is why the PREVENT calculator includes kidney function (see risk calculators).

Insulin resistance comes first#

Insulin moves glucose from the blood into muscle, liver, and fat. In insulin resistance those tissues respond less, so the pancreas makes more insulin to compensate, and for years glucose stays normal while insulin runs high. People with type 2 diabetes may initially have normal or elevated insulin even as glucose control fails.

The timeline is long, and it starts young. In the Whitehall II study of 6,538 British civil servants, insulin sensitivity fell steeply over the five years before a diabetes diagnosis, while fasting glucose rose sharply only in the final three. In national surveys of 6,247 adults aged 18 to 44, 40% had insulin resistance (a HOMA-IR of 2.5 or more), and nearly half of them did not have obesity. Drivers include visceral fat (fat around the organs), inactivity, poor sleep, some medications, and genes; the fixes are in Exercise, Nutrition, and Sleep.

Tests that catch it early#

Because glucose rises late, the optimal plan pairs glucose tests with insulin tests and repeats them every year, on the same blood draw as your lipid panel. Prevention-focused physicians such as Peter Attia measure insulin, not just glucose, and go further with a glucose tolerance test and a continuous glucose monitor. No US guideline uses insulin tests; guidelines diagnose diabetes with glucose and HbA1c only.

High insulin is more than a marker. In a Quebec study of men without heart disease, fasting insulin was 18% higher in those who went on to develop it, independent of LDL, ApoB, and triglycerides. Moderate In 258 overweight adults, a triglyceride-to-HDL ratio of 3.0 or more or a fasting insulin of about 18 µIU/mL or more each caught roughly 57–67% of people with insulin resistance: useful, not definitive. Targets are in Metabolic markers at a glance.

Prediabetes and type 2 diabetes#

Diagnosis#

The ADA's 2026 Standards of Care use these cutoffs. Without obvious symptoms, an abnormal result needs a repeat or a second test.

In 2023, 27.6% of adults with diabetes were undiagnosed, and about half of people 65 and older had prediabetes.

Who should be screened#

Optimal: everyone, every year, from your 20s. Get an HbA1c and fasting glucose with your annual blood work, add fasting insulin, and recheck every 3 months while you change your diet, training, weight, or medication. In Whitehall II, fasting glucose climbed steeply only in the three years before diagnosis, so a three-year gap between tests can miss the whole rise. Moderate

Guideline minimum:

• ADA (2026): test everyone from age 35, and adults of any age with overweight or obesity plus a risk factor such as a close relative with diabetes, high blood pressure, or fatty liver. Repeat at least every three years if normal, more often depending on results and risk, and at least yearly with prediabetes.
• USPSTF (2021): screen adults aged 35 to 70 with overweight or obesity (BMI 25 or higher, or 23 or higher for Asian Americans), grade B; every three years may be reasonable if normal.

Prevention works#

The Diabetes Prevention Program randomized 3,234 adults with prediabetes to placebo, metformin, or a lifestyle program aiming for at least 7% weight loss and 150 minutes of activity a week. Over about three years, new diabetes fell from 11.0 to 4.8 cases per 100 person-years with lifestyle (58% lower) and to 7.8 with metformin (31% lower). About seven people needed the lifestyle program to prevent one case, versus 14 for metformin. Strong

When to add a drug#

Lifestyle comes first, but optimal care does not wait years for it to fail. Recheck HbA1c about three months after a serious change; if it has not moved, ask about medication.

• Prediabetes at high risk. The ADA advises considering metformin, especially at ages 25 to 59 with a BMI of 35 or more, fasting glucose of 110 mg/dL or more, HbA1c of 6.0% or more, or prior gestational diabetes, with periodic vitamin B12 checks. Strong
• Prediabetes or insulin resistance with obesity. A GLP-1 drug is the stronger option if you qualify (a BMI of 30 or more, or 27 or more with a weight-related condition). In 1,032 adults with obesity and prediabetes, three years of tirzepatide cut weight by 12–20% and new diabetes from 13.3% to 1.3%, in a trial funded by its maker. The ADA now says weight-management drugs should be considered for people at high risk. Strong
• Insulin resistance with normal glucose and weight. No drug has outcome data here. Training, losing visceral fat, and better sleep are the treatment; retest in three to six months rather than starting metformin or berberine for a high insulin reading alone.

Obesity beyond BMI#

About 40.3% of US adults had obesity in 2021–2023, and 9.4% had severe obesity. But body mass index (BMI, weight divided by height squared) cannot tell muscle from fat or show where fat sits.

A 2025 Lancet Diabetes & Endocrinology commission, endorsed by 76 organizations, proposed a new framework: BMI serves only as a screen, with excess fat confirmed by a waist measure or direct body-fat measurement (except above a BMI of 40). Obesity is then preclinical (excess fat, organs still working normally) or clinical, a disease of fat-related organ dysfunction or limits on daily activities that warrants treatment.

Waist-to-height ratio#

The simplest number to track is your waist divided by your height. Aim for under 0.5, and measure every few months just above the belly button, midway between ribs and hips, after breathing out. The UK's NICE guideline uses the same threshold: 0.4–0.49 is healthy, 0.5–0.59 signals increased risk, and 0.6 or more high risk. An international working group calls waist a vital sign and a shrinking waist a treatment target in itself. A 70-inch man with a 38-inch waist scores 0.54. Moderate

Guideline minimum: US guidelines use waist only in the metabolic syndrome cutoffs above, 40 inches for men and 35 for women, which flag risk far later.

Body fat and visceral fat#

A whole-body DEXA scan, a very low-dose X-ray, measures fat, lean mass, and bone, and estimates visceral fat, the deep abdominal fat most tied to insulin resistance. Visceral fat measured by CT or MRI is an independent marker of heart and metabolic disease. Track it as a number: get a body-composition DEXA in your 30s or 40s and repeat it every one to two years on the same machine, aiming for visceral fat that is low and falling while lean mass holds. DEXA visceral fat is an estimate with no validated cutoff, so the trend matters more than any one reading. Weak The schedule and lean-mass targets are in Measuring sarcopenia, and the scan itself in Scans and imaging.

Fatty liver disease#

In 2023, liver societies renamed nonalcoholic fatty liver disease metabolic dysfunction-associated steatotic liver disease (MASLD): excess liver fat plus at least one of five cardiometabolic risk factors. The inflamed, scarring form is MASH, and fatty liver with moderate drinking (140–350 g of alcohol a week for women, 210–420 g for men) is MetALD.

MASLD affects about 30% of adults worldwide, 38% in the most recent period studied, and usually causes no symptoms. What matters is fibrosis, the scarring that can progress to cirrhosis and liver cancer, although people with MASLD die of heart disease more often than of liver disease. Standard lab ranges hide early disease: the American College of Gastroenterology considers a normal ALT to be 29–33 U/L for men and 19–25 for women, well below the 40 that many labs flag.

Screening with FIB-4#

FIB-4 is a free score calculated from age, two liver enzymes (AST and ALT), and platelet count, all on routine blood work.

Optimal: calculate it every year from 35, from the metabolic panel and blood count you already get, even if your liver enzymes are normal. It costs nothing extra, and fatty liver is common enough that waiting for a risk label misses people. Weak

Guideline minimum:

• ADA (2026): screen adults with type 2 diabetes or prediabetes, especially with obesity or other cardiometabolic risk factors, even if liver enzymes are normal. Strong
• AASLD (2023): screen people with type 2 diabetes, obesity with metabolic complications, moderate drinking with fatty liver, or a parent or sibling with MASH cirrhosis, and repeat every one to two years with prediabetes, diabetes, or two or more metabolic risk factors.
• European societies (2024): look for fibrosis in anyone with cardiometabolic risk factors, abnormal liver enzymes, or fat on imaging, using FIB-4 first and a stiffness scan second.

A FIB-4 below 1.3 means low risk of advanced fibrosis. At 1.3 or higher, the next step is a painless liver stiffness scan, usually vibration-controlled transient elastography (FibroScan), where a reading below 8.0 kPa is reassuring; see liver elastography. Above 2.67, see a liver specialist. FIB-4 is not validated under age 35, and a cutoff of about 2.0 applies at 65 and older.

Treatment#

Weight loss is the core treatment: 3–5% reduces liver fat, and more than 10% is generally needed to improve MASH and fibrosis. Alcohol worsens every stage (see Avoiding harm), three or more cups of coffee a day is linked to less advanced disease in observational studies, and bariatric surgery resolved MASH in about 80% of patients at one year in one study.

Two drugs are FDA approved for MASH with moderate to advanced fibrosis (stages F2 to F3, without cirrhosis), both under accelerated approval pending outcome data:

• Resmetirom (Rezdiffra), a daily pill, approved March 14, 2024. In 966 patients, MASH resolved in 26–30% versus 10% on placebo, and fibrosis improved in 24–26% versus 14%. Moderate
• Semaglutide (Wegovy), approved for MASH on August 15, 2025. In the first 800 patients of the ESSENCE trial, MASH resolved in 62.9% versus 34.3%, and fibrosis improved in 36.8% versus 22.4%. Moderate

For type 2 diabetes with MASH, the ADA prefers a GLP-1 drug for glucose control, with pioglitazone or tirzepatide as alternatives.

Kidneys, gout, and uric acid#

Kidney health#

About 14% of US adults, roughly 37 million people, have chronic kidney disease (CKD), and 87% of them don't know it; it affects 38% of adults with diabetes and 21% with high blood pressure. CKD means an eGFR below 60 or a urine albumin-to-creatinine ratio of 30 mg/g or higher for at least three months, and it raises the risk of heart attack, stroke, and heart failure long before kidneys fail.

Optimal: test everyone every year with two cheap markers, on the same draw as your annual labs:

• eGFR from creatinine plus cystatin C. eGFR (estimated glomerular filtration rate) comes from blood creatinine, using a 2021 equation without race. Creatinine depends on muscle mass, so it misleads in muscular, very lean, and older people. Across 11 general-population cohorts, adding cystatin C, a second blood marker, found more kidney disease (13.7% versus 9.7% with an eGFR under 60) and predicted death and kidney failure better; KDIGO, the international kidney guideline group, advises it when creatinine is less accurate.
• Urine albumin-to-creatinine ratio (uACR). A spot urine test for protein leaking into urine, often the earliest sign of damage; risk rises even within the normal range. Skip hard exercise for 24 hours beforehand, since exercise, fever, infection, and menstruation can raise it temporarily, and confirm an abnormal result with repeat tests.

Screening adults for albuminuria was cost-effective in a 2023 US model even from a public-budget view, because SGLT2 inhibitors now slow CKD; yearly testing of healthy people is expert practice. Weak

Guideline minimum:

• Type 2 diabetes: uACR and eGFR at least yearly (ADA). Strong
• Other risk factors: KDIGO advises testing with both for high blood pressure, cardiovascular disease, prior acute kidney injury, or a family history of kidney disease, and the 2025 blood pressure guideline made uACR routine with hypertension. Moderate
• Everyone else: creatinine-based eGFR comes with routine blood work; no guideline adds cystatin C or uACR.

Protecting your kidneys mostly means controlling blood pressure and glucose. With CKD, SGLT2 inhibitors slow progression (see below) and protein needs may be lower (Nutrition).

Gout and uric acid#

Gout, a painful arthritis caused by uric acid crystals in joints, affected 3.9% of US adults (9.2 million) in 2015–2016, and about 20% had high blood uric acid. Uric acid is cheap to add to your yearly labs, and it tracks metabolic health: in 22,714 Italian adults followed for up to 20 years, levels above about 4.7 mg/dL predicted higher overall mortality and above 5.6 higher cardiovascular mortality (observational). Keep it low with weight loss, little or no alcohol, and fewer sugary drinks. Weak

Optimal does not mean drugs. Allopurinol did not reduce heart attacks, strokes, or cardiovascular deaths in 5,721 people with heart disease and no gout (11.0% versus 11.3% over about five years) Negative, and the American College of Rheumatology advises against starting drugs for high uric acid without gout. With gout, its target is below 6 mg/dL on urate-lowering drugs, and it conditionally recommends limiting alcohol, purine-rich foods, and high-fructose corn syrup, losing weight if needed, and skipping vitamin C supplements.

GLP-1 and dual agonists#

GLP-1 receptor agonists mimic a gut hormone that slows stomach emptying, reduces appetite, and boosts insulin release when glucose is high. Tirzepatide also activates the GIP receptor, making it a dual agonist. In trials they cut body weight by 11–21% over 64 to 72 weeks, and the evidence for their benefits is strong. Strong When they make sense before diabetes is covered in When to add a drug.

What is approved#

Dates are from the FDA's Drugs@FDA database, as of October 2026.

The obesity versions are approved for adults with a BMI of 30 or more, or 27 or more with a weight-related condition (Wegovy label). Using them below those thresholds for cosmetic weight loss adds side effects and muscle loss without proven benefit. The Wegovy pill is taken on an empty stomach with a little water, 30 minutes before food or other medicines; Foundayo, a non-peptide molecule, can be taken with or without food.

What the outcome trials show#

• SELECT (2023): in 17,604 adults with heart disease and overweight or obesity but no diabetes, semaglutide lowered heart attack, stroke, or cardiovascular death from 8.0% to 6.5% over about three years, a 20% relative reduction.
• SURPASS-CVOT (2025): in 13,299 adults with type 2 diabetes and heart disease, tirzepatide matched dulaglutide, an older GLP-1 drug with proven heart benefit (12.2% vs 13.1% events).
• Kidneys and liver: the ADA recommends a GLP-1 drug with proven benefit for type 2 diabetes with CKD, and semaglutide improved MASH in ESSENCE.

Heart failure results are in Heart and blood vessels, and whether these drugs slow aging itself is in Longevity drugs.

Side effects and who should avoid them#

Nausea, vomiting, diarrhea, and constipation are common, especially while the dose is being raised: gastrointestinal side effects affected 74% versus 42% on placebo in the Wegovy pill trial, and side effects led 16.6% of people in SELECT to stop, versus 8.2%.

Protecting muscle#

Some of the weight lost is lean mass: across trials, about 15% to 40–60% of it, although lean mass includes organs and water, and muscle quality may improve. Older adults and people at risk of sarcopenia need the most care.

The ADA advises guarding against protein insufficiency and pairing protein with resistance training, and a 2025 joint advisory from four nutrition and obesity societies recommends assessing strength and body composition at the start. In practice: get a DEXA scan before you start and every 6 to 12 months while losing weight, lift three times a week, eat about 1.6 g of protein per kilogram of body weight even when appetite is low, and track strength, not just weight. See Training on GLP-1 drugs and Protein.

What happens when you stop#

Like blood pressure pills, they help while you take them.

• A year after stopping semaglutide in STEP 1, 327 participants had regained about two-thirds of the weight they lost, and most cardiometabolic improvements reversed.
• In SURMOUNT-4, 670 adults who lost about 21% on tirzepatide were randomized to continue or switch to placebo. Over the next year, those who stopped regained 14% of their body weight, while those who continued lost another 5.5%.

The ADA advises continuing obesity medicine beyond reaching your goal; tapering to a lower maintenance dose is common but little tested.

Compounded versions#

The FDA declared the tirzepatide and semaglutide shortages over on December 19, 2024 and February 21, 2025, so compounders generally may no longer copy approved products. Compounded drugs are not FDA reviewed, and by May 31, 2026, the FDA had received 990 adverse event reports for compounded semaglutide and more than 730 for tirzepatide. With approved versions from about $149 a month, the case for compounded ones is weak.

Cost as of October 2026#

List prices remain over $1,000 a month, but direct-to-patient prices have fallen sharply. Prices change often; check before you buy.

Insurance coverage is in Building your care team.

Metformin, SGLT2 inhibitors, and surgery#

Metformin is the usual first drug for type 2 diabetes and an option for preventing it in high-risk prediabetes, as above. Strong Its case as an anti-aging drug for healthy people is weaker; see Longevity drugs.

SGLT2 inhibitors (empagliflozin, dapagliflozin, canagliflozin) make the kidneys excrete glucose. The ADA recommends them for type 2 diabetes with CKD from an eGFR of 20. In EMPA-KIDNEY, 6,609 people with CKD, with or without diabetes, had kidney progression or cardiovascular death cut from 16.9% to 13.1% over two years. Strong Labeled risks include genital yeast and urinary infections, dehydration, and ketoacidosis even at normal glucose, which is why fasting on them is risky. Heart failure use is in Heart and blood vessels, the aging angle in Longevity drugs.

Berberine, sold as "nature's metformin," modestly lowered HbA1c in trials in type 2 diabetes; see Supplements. Moderate

Bariatric surgery remains the most powerful treatment for severe obesity. In the Swedish Obese Subjects study, 2,007 surgery patients followed for a median of 24 years had 23% lower mortality than controls and lived about three years longer. The ADA supports surgery for type 2 diabetes from a BMI of 30 (27.5 for Asian Americans), noting perioperative mortality of about 0.1–0.5% and a lifelong need for vitamin and mineral monitoring. Strong

Metabolic markers at a glance#

Guideline cutoffs diagnose disease; optimal targets sit well inside the normal range, where risk is lowest. Full ranges and costs are in Blood tests and biomarkers.

Action plan#