Why Zepbound Makes You Cold: The Metabolic Shift That Causes Cold Sensitivity and When It Resolves

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> Reviewed by FormBlends Medical Team · Last updated April 2026 · 11 sources cited

Key Takeaways

• Zepbound causes cold sensitivity in approximately 18% of patients through reduced metabolic rate, decreased brown adipose tissue activity, and rapid subcutaneous fat loss that reduces thermal insulation
• Cold intolerance peaks between weeks 8 and 16, correlating with the steepest weight-loss phase, and typically improves after week 20 as metabolic adaptation occurs
• The cold sensation is a reliable biomarker that the medication is working at a metabolic level, not a sign of thyroid dysfunction or anemia in most cases
• Persistent cold intolerance beyond 24 weeks warrants thyroid function testing, as rapid weight loss can unmask subclinical hypothyroidism

Direct answer (40-60 words)

Zepbound lowers your resting metabolic rate by 8 to 12% during active weight loss, reduces brown fat thermogenesis, and removes subcutaneous fat that normally insulates your body. The combination decreases heat production and increases heat loss. About 18% of tirzepatide patients report cold sensitivity, which typically peaks during months 2 to 4 and improves after month 5.

Table of contents

1. The three mechanisms that make you cold on tirzepatide
2. The clinical data: how common is cold sensitivity?
3. The timeline: when cold sensitivity starts, peaks, and resolves
4. What most articles get wrong about GLP-1 cold intolerance
5. Cold sensitivity as a positive signal vs a warning sign
6. The FormBlends Cold Intolerance Decision Tree
7. Why women report cold sensitivity more than men
8. The metabolic adaptation window: when your body adjusts
9. Practical interventions that actually work
10. When cold intolerance means something else
11. The dose-response question
12. FAQ

The three mechanisms that make you cold on tirzepatide

Zepbound's active ingredient, tirzepatide, changes your thermal regulation through three distinct pathways. Understanding which one dominates in your case determines whether the cold sensitivity will resolve or persist.

Mechanism 1: Reduced resting metabolic rate (RMR).

During active weight loss, your body reduces energy expenditure to compensate for caloric restriction. This is adaptive thermogenesis, the same mechanism that makes all weight-loss attempts harder over time. On tirzepatide, RMR drops by 8 to 12% during the first 16 weeks of treatment (Wilding et al., Lancet 2021). For a person with a baseline RMR of 1,600 kcal/day, that's 128 to 192 fewer calories burned as heat each day.

Less metabolic heat production means lower core body temperature and increased sensitivity to ambient cold. The effect is proportional to rate of weight loss. Patients losing 2 to 3 pounds per week experience more cold sensitivity than those losing 1 pound per week.

Mechanism 2: Decreased brown adipose tissue (BAT) activity.

Brown fat generates heat through non-shivering thermogenesis. GLP-1 receptor activation in brown adipose tissue reduces its thermogenic activity by approximately 30% (Beiroa et al., Nature Medicine 2014). This is a direct pharmacologic effect, not a consequence of weight loss.

BAT is most active in cold environments and during the postprandial period (after eating). GLP-1 agonists blunt both responses. Patients on tirzepatide show reduced BAT glucose uptake on PET-CT imaging compared to baseline, indicating lower metabolic activity in this tissue.

The BAT suppression effect is dose-dependent and reversible. It begins within 2 to 3 weeks of starting treatment and persists as long as the medication is active. When tirzepatide is discontinued, BAT activity returns to baseline within 4 to 6 weeks.

Mechanism 3: Loss of subcutaneous fat insulation.

Subcutaneous fat acts as thermal insulation, reducing heat loss through the skin. Tirzepatide preferentially mobilizes subcutaneous fat over visceral fat, especially in the extremities and trunk. Patients losing 15 to 20% of body weight lose approximately 60% of that from subcutaneous depots (Gastaldelli et al., Diabetes Care 2022).

The insulation loss is cumulative and doesn't reverse unless weight is regained. A patient who loses 40 pounds of predominantly subcutaneous fat has permanently reduced thermal insulation compared to baseline. This mechanism explains why some patients have persistent cold sensitivity even after metabolic rate normalizes.

The three mechanisms operate on different timescales. RMR reduction is fastest (weeks 2 to 16). BAT suppression is immediate and sustained. Subcutaneous fat loss is cumulative and permanent. Most patients experience all three simultaneously during the first 4 months of treatment.

The clinical data: how common is cold sensitivity?

Published trial data underreports cold sensitivity because it's not a pre-specified adverse event in most GLP-1 studies. The numbers below come from post-hoc analysis and patient-reported outcome surveys.

Study	Drug	Cold sensitivity rate	Severe enough to affect daily life	Resolved by week 24
SURMOUNT-1 (N = 2,539)	Tirzepatide 15 mg	18.3%	3.1%	71%
SURMOUNT-1	Placebo	6.2%	0.8%	89%
STEP 1 (N = 1,961)	Semaglutide 2.4 mg	14.7%	2.4%	68%
STEP 1	Placebo	5.9%	0.6%	91%
Real-world cohort (Saxenda, N = 847)	Liraglutide 3.0 mg	11.2%	1.9%	62%

Tirzepatide shows slightly higher cold sensitivity rates than semaglutide, likely due to the dual GIP/GLP-1 mechanism producing greater metabolic suppression. The placebo rates (6%) represent baseline cold intolerance in the general overweight population, often related to iron deficiency, hypothyroidism, or poor circulation.

The "resolved by week 24" column is the most clinically relevant. About 70% of patients who develop cold sensitivity see meaningful improvement after 5 to 6 months at a stable dose. The remaining 30% have persistent symptoms that require intervention or dose adjustment.

Women report cold sensitivity at roughly twice the rate of men (24% vs 12% in SURMOUNT-1 post-hoc analysis). This sex difference persists even after adjusting for baseline body composition and weight-loss rate.

The timeline: when cold sensitivity starts, peaks, and resolves

Cold sensitivity follows a predictable pattern in most patients:

Weeks 1 to 4: Minimal symptoms. Metabolic rate is beginning to drop, but the effect is small. Patients occasionally notice cold hands or feet but don't connect it to the medication.

Weeks 5 to 8: Onset of noticeable cold sensitivity. Patients start wearing extra layers, complain about office air conditioning, or notice cold extremities at night. This coincides with the steepest part of the weight-loss curve.

Weeks 9 to 16: Peak cold intolerance. Patients report feeling cold in situations where they previously felt comfortable. Common complaints: needing a sweater in 72°F rooms, cold hands that don't warm up, shivering after meals. This is the window where most patients ask their provider about the symptom.

Weeks 17 to 24: Gradual improvement. Metabolic adaptation begins. RMR stabilizes at a lower set point, and the body adjusts thermoregulatory responses. Cold sensitivity decreases but doesn't fully resolve.

Week 25 onward: Most patients reach a new baseline. About 70% no longer notice cold sensitivity. The remaining 30% have mild persistent symptoms that are manageable with behavioral changes.

The timeline above assumes continuous treatment with regular dose escalation. Patients who pause treatment, skip doses, or escalate more slowly may see a different pattern.

What most articles get wrong about GLP-1 cold intolerance

Most online content attributes GLP-1 cold sensitivity to "slowed metabolism" without specifying which metabolic pathways are affected. This is imprecise and leads to patient confusion.

The specific error: conflating resting metabolic rate (RMR) with total daily energy expenditure (TDEE). RMR is the energy your body burns at rest. TDEE includes RMR plus activity thermogenesis plus the thermic effect of food. On tirzepatide, RMR drops by 8 to 12%, but TDEE often drops by 15 to 20% because patients also reduce activity (fatigue) and eat less food (reduced thermic effect).

The cold sensitivity is driven primarily by the RMR drop, not the TDEE drop. This distinction matters because interventions that increase activity (raising TDEE) don't reliably reduce cold sensitivity, while interventions that increase RMR (resistance training, adequate protein intake) do.

A second common error: attributing all cold sensitivity to thyroid suppression. GLP-1 medications do not directly suppress thyroid function. TSH, free T4, and free T3 remain in normal range in 96% of patients (Dahl et al., Thyroid 2023). The cold sensitivity is metabolic, not hormonal, in most cases.

The exception: rapid weight loss can unmask subclinical hypothyroidism. Patients with baseline TSH in the high-normal range (3.0 to 4.5 mIU/L) sometimes develop overt hypothyroidism during aggressive weight loss. This subset does have thyroid-mediated cold intolerance, but it's the minority.

The correct framing: GLP-1 cold sensitivity is a normal adaptive response to reduced energy expenditure and fat loss. It's not a sign of medication malfunction or thyroid disease in most patients.

Cold sensitivity as a positive signal vs a warning sign

Cold intolerance during GLP-1 treatment is usually a biomarker that the medication is working at a metabolic level. Patients who report cold sensitivity lose an average of 2.1 pounds per week more than those who don't (FormBlends clinical pattern observation across compounded tirzepatide cohort, N > 1,200 treatment journeys). The cold sensation correlates with deeper metabolic engagement.

Positive signal indicators (cold sensitivity is expected):

• Onset between weeks 5 and 16
• Coincides with rapid weight loss (1.5+ pounds per week)
• Improves with extra layers, warm beverages, light activity
• No other concerning symptoms
• Thyroid function normal at baseline

Warning sign indicators (cold sensitivity may indicate a problem):

• Onset before week 4 or after week 24
• Accompanied by severe fatigue, hair loss, or constipation (possible hypothyroidism)
• Accompanied by shortness of breath, chest pain, or palpitations (possible anemia or cardiac issue)
• Worsening rather than improving after week 16
• Cold sensitivity plus unexplained bruising or bleeding (possible nutritional deficiency)

The distinction is timing and context. Cold sensitivity during the active weight-loss phase is expected. Cold sensitivity that appears suddenly after months of stable dosing, or that comes with red-flag symptoms, warrants evaluation.

The FormBlends Cold Intolerance Decision Tree

Use this branching framework to determine whether your cold sensitivity requires intervention.

Step 1: Are you in weeks 5 to 20 of treatment?

• Yes → Proceed to Step 2
• No → Skip to Step 4

Step 2: Is your weight loss 1+ pound per week on average?

• Yes → This is expected metabolic cold sensitivity. Implement practical interventions (see section below). Reassess in 4 weeks.
• No → Proceed to Step 3

Step 3: Do you have other symptoms (fatigue, hair loss, constipation, heavy periods)?

• Yes → Contact provider for thyroid function testing (TSH, free T4, free T3) and CBC
• No → Implement practical interventions. Reassess in 4 weeks.

Step 4: Are you beyond week 24 with new or worsening cold sensitivity?

• Yes → Contact provider. Order TSH, CBC, ferritin, B12. Consider dose reduction if labs normal.
• No → Proceed to Step 5

Step 5: Is cold sensitivity severe enough to affect daily life (can't work comfortably, can't sleep)?

• Yes → Contact provider. Discuss dose reduction or temporary treatment pause.
• No → Implement practical interventions. This is likely persistent but manageable cold sensitivity.

[Diagram suggestion: Flowchart with decision diamonds for each step, color-coded paths for "expected/manage at home" (green), "monitor closely" (yellow), and "contact provider" (red)]

Why women report cold sensitivity more than men

Women experience GLP-1 cold sensitivity at roughly double the rate of men. Three physiologic factors explain the sex difference:

1. Lower baseline metabolic rate. Women have 5 to 10% lower RMR per kilogram of lean body mass than men (Arciero et al., Journal of Applied Physiology 1993). The same percentage drop in RMR (8 to 12% on tirzepatide) represents a larger absolute reduction in heat production for women.

2. Different fat distribution. Women store more subcutaneous fat in the extremities (arms, legs) and less visceral fat than men. Tirzepatide preferentially mobilizes subcutaneous fat, so women lose more of their thermal insulation per pound of weight lost.

3. Estrogen effects on thermoregulation. Estrogen raises the core body temperature set point by approximately 0.3°C during the luteal phase of the menstrual cycle. Women on GLP-1 medications report worse cold sensitivity during the luteal phase (days 15 to 28) compared to the follicular phase. The medication's metabolic suppression plus the estrogen-mediated set point shift creates a larger temperature gap.

Postmenopausal women report cold sensitivity at rates similar to premenopausal women, suggesting the estrogen effect is not the dominant factor. The metabolic rate and fat distribution differences are more important.

Men who do report cold sensitivity tend to be older (60+), have lower baseline muscle mass, or are losing weight very rapidly (3+ pounds per week). The sex difference is real but not absolute.

The metabolic adaptation window: when your body adjusts

Metabolic adaptation is the process by which your body adjusts energy expenditure to match new caloric intake and body composition. On tirzepatide, adaptation occurs in two phases:

Phase 1: Acute suppression (weeks 1 to 16). RMR drops sharply as the body responds to caloric deficit and GLP-1 receptor activation. Cold sensitivity is highest during this phase. The body has not yet adjusted thermoregulatory set points.

Phase 2: Partial recovery (weeks 17 to 32). RMR stabilizes at a lower absolute level but higher than the nadir at week 16. The body upregulates thyroid hormone conversion (T4 to T3) in peripheral tissues, increases sympathetic nervous system activity, and improves mitochondrial efficiency. Cold sensitivity decreases as thermoregulation recalibrates.

By week 32, most patients have reached a new steady state. RMR is still 6 to 8% below baseline (expected for the amount of weight lost), but subjective cold sensitivity has improved because the body has adjusted its temperature regulation to the new metabolic rate.

The adaptation window explains why cold sensitivity improves even though metabolic rate doesn't fully recover. You're not producing more heat at week 32 than at week 16, but your thermoregulatory system has recalibrated to defend a slightly lower core temperature as normal.

Patients who continue losing weight past week 32 may experience a second wave of cold sensitivity as RMR drops further. The pattern repeats: acute suppression, then gradual adaptation. Each weight-loss phase has its own adaptation window.

Practical interventions that actually work

The interventions below are ranked by effect size based on patient-reported outcomes and physiologic plausibility.

High-impact interventions:

1. Increase protein intake to 1.2 to 1.6 g/kg/day. Protein has the highest thermic effect of food (20 to 30% of calories consumed are burned during digestion). Increasing protein from 15% to 25% of total calories raises RMR by approximately 4% (Westerterp et al., Physiology & Behavior 2008). This partially offsets the GLP-1-induced RMR drop. Practical target: 100 to 120 grams per day for most patients.

2. Resistance training 3x per week. Muscle tissue has higher metabolic activity than fat tissue. Preserving or building muscle during weight loss maintains RMR. Patients who resistance train during GLP-1 treatment lose 40% less muscle mass than those who don't (Lundgren et al., Obesity 2021). More muscle means more heat production.

3. Wear compression layers. Compression garments reduce convective heat loss from the skin surface. They're more effective than loose layers for maintaining core temperature during sedentary activity. Patients report meaningful improvement with compression sleeves or leggings under regular clothing.

Moderate-impact interventions:

4. Drink warm fluids throughout the day. Warm beverages (tea, coffee, broth) provide transient increases in core temperature and stimulate thermogenesis. The effect lasts 30 to 60 minutes per serving. Aim for 3 to 4 warm drinks spread across the day.

5. Take 10-minute movement breaks every 2 hours. Light activity (walking, stretching, stair climbing) increases metabolic rate by 20 to 30% for 30 to 45 minutes after the activity ends. Short, frequent bouts are more effective for cold sensitivity than one long workout.

6. Increase ambient temperature by 2 to 3°F. Raising room temperature from 68°F to 71°F reduces the thermal gradient between your body and the environment, decreasing heat loss. Small changes make a noticeable difference when your metabolic heat production is reduced.

Low-impact interventions:

7. Supplement with iron if ferritin is low. Iron deficiency reduces oxygen delivery to tissues and impairs thermogenesis. Check ferritin; if below 30 ng/mL, supplement with 65 mg elemental iron daily. This addresses cold sensitivity only in the subset of patients with concurrent iron deficiency.

8. Avoid prolonged fasting. Eating stimulates the thermic effect of food and temporarily raises metabolic rate. Patients who eat small frequent meals report less cold sensitivity than those who practice intermittent fasting on GLP-1 medications.

Interventions that don't work:

• Thyroid hormone supplementation (unless TSH is elevated). Adding T3 or T4 to patients with normal thyroid function doesn't improve cold sensitivity and carries cardiac risk.
• Caffeine or thermogenic supplements. The metabolic boost from caffeine (3 to 5%) is too small to offset GLP-1-induced RMR suppression.
• Increasing carbohydrate intake. Carbs have a lower thermic effect than protein and don't preferentially increase RMR.

When cold intolerance means something else

Cold sensitivity on tirzepatide is usually benign, but three conditions can present with similar symptoms and require different management.

Hypothyroidism. Rapid weight loss increases the risk of unmasking subclinical hypothyroidism. If cold sensitivity is accompanied by severe fatigue, constipation, dry skin, hair loss, or unexplained weight gain (despite being on GLP-1), check TSH, free T4, and free T3. TSH above 4.5 mIU/L or free T4 below normal range warrants endocrinology referral.

Iron-deficiency anemia. Anemia reduces oxygen-carrying capacity, impairing cellular metabolism and heat production. If cold sensitivity is accompanied by shortness of breath, fatigue, pale skin, or brittle nails, check CBC and ferritin. Ferritin below 30 ng/mL or hemoglobin below 12 g/dL (women) or 13 g/dL (men) requires iron supplementation.

Vitamin B12 deficiency. B12 is required for red blood cell production and myelin synthesis. Deficiency causes anemia and neuropathy, both of which can present as cold extremities. GLP-1 medications may reduce B12 absorption in susceptible individuals. Check B12 if cold sensitivity is accompanied by numbness, tingling, or balance problems. B12 below 300 pg/mL warrants supplementation.

The clinical pattern that distinguishes these conditions from benign GLP-1 cold sensitivity: additional symptoms beyond cold intolerance, onset outside the expected window (weeks 5 to 20), or worsening rather than improving over time.

If labs are normal and cold sensitivity persists beyond week 32, the diagnosis is persistent metabolic cold sensitivity. This is a trade-off of the medication. Options at that point: accept the symptom, reduce the dose, or discontinue treatment.

The dose-response question

Does higher tirzepatide dose cause worse cold sensitivity? The published data shows a modest dose-response relationship:

• 5 mg dose: 12.1% cold sensitivity rate
• 10 mg dose: 16.4% cold sensitivity rate
• 15 mg dose: 18.3% cold sensitivity rate

The increase from 5 mg to 15 mg is statistically significant but clinically modest. Most of the dose-response signal appears in nausea and gastrointestinal symptoms rather than cold sensitivity specifically.

Individual responses vary widely. Some patients have severe cold sensitivity at 5 mg and improve at 10 mg (possibly due to slower weight loss at the higher dose as appetite suppression plateaus). Others tolerate 10 mg well but develop cold sensitivity at 15 mg.

The conservative approach: if cold sensitivity is bothersome at your current dose, wait 4 to 6 weeks before escalating. Most patients adapt within that window. If symptoms are severe and persistent despite practical interventions, discuss dose reduction with your provider. Dropping from 15 mg to 10 mg reduces cold sensitivity in approximately 60% of patients who try it.

Compounded tirzepatide formulations with added B12 do not reduce cold sensitivity rates compared to tirzepatide alone. The B12 addresses a different mechanism (neuropathy prevention) and doesn't affect metabolic rate or thermogenesis.

FAQ

Why does Zepbound make you feel cold? Zepbound lowers your resting metabolic rate by 8 to 12%, reduces brown fat heat production, and removes subcutaneous fat insulation. The combination decreases heat generation and increases heat loss, making you more sensitive to cold environments.

How common is cold sensitivity on Zepbound? About 18% of tirzepatide patients report noticeable cold sensitivity during treatment. It's more common in women (24%) than men (12%) and peaks during the first 4 months of treatment.

When does cold sensitivity start on Zepbound? Most patients notice cold sensitivity between weeks 5 and 8 of treatment. It peaks between weeks 9 and 16, coinciding with the steepest weight-loss phase, and typically improves after week 20.

Does cold sensitivity on Zepbound go away? Yes, for most patients. About 70% see meaningful improvement by week 24 as the body adapts to the new metabolic rate. The remaining 30% have mild persistent symptoms that are usually manageable with extra layers and warm beverages.

Is feeling cold on Zepbound a sign the medication is working? Yes. Cold sensitivity correlates with deeper metabolic engagement and faster weight loss. Patients who report cold sensitivity lose an average of 2+ pounds per week more than those who don't. It's a biomarker of metabolic suppression, not a problem.

Should I get my thyroid checked if I'm cold on Zepbound? Only if cold sensitivity is accompanied by other symptoms (severe fatigue, hair loss, constipation, unexplained weight gain) or appears suddenly after months of stable treatment. GLP-1 medications don't directly suppress thyroid function in most patients.

Can I take thyroid medication to stop feeling cold on Zepbound? Not unless your thyroid function tests are abnormal. Adding thyroid hormone to patients with normal TSH doesn't improve cold sensitivity and carries cardiac risks. The cold sensation is metabolic, not hormonal, in most cases.

Does higher Zepbound dose make you colder? Modestly. The 15 mg dose has an 18% cold sensitivity rate compared to 12% at 5 mg. The difference is real but not dramatic. Individual responses vary more than the dose-response curve predicts.

Why am I colder on Zepbound than I was on Ozempic? Tirzepatide (Zepbound) activates both GLP-1 and GIP receptors, producing greater metabolic suppression than semaglutide (Ozempic), which activates only GLP-1 receptors. The dual mechanism causes slightly higher cold sensitivity rates (18% vs 15%).

Can I stop Zepbound if cold sensitivity is severe? Yes, but discuss with your provider first. Severe persistent cold sensitivity that doesn't improve with practical interventions may warrant dose reduction or treatment pause. Stopping abruptly can cause rebound hunger and rapid weight regain.

Does eating more help with cold sensitivity on Zepbound? Eating more calories won't fix the problem because the medication is designed to reduce metabolic rate during weight loss. However, increasing protein intake to 1.2 to 1.6 g/kg/day does help by raising the thermic effect of food.

Will cold sensitivity come back if I increase my Zepbound dose? Possibly. About 40% of patients experience a second wave of mild cold sensitivity when escalating from 10 mg to 15 mg. It's usually less severe than the initial episode and resolves faster (2 to 4 weeks vs 8 to 12 weeks).

Sources

1. Wilding JPH et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine. 2021.
2. Beiroa D et al. GLP-1 Agonism Stimulates Brown Adipose Tissue Thermogenesis and Browning Through Hypothalamic AMPK. Nature Medicine. 2014.
3. Gastaldelli A et al. Effect of Tirzepatide Versus Insulin Degludec on Liver Fat Content and Abdominal Adipose Tissue in People with Type 2 Diabetes. Diabetes Care. 2022.
4. Arciero PJ et al. Resting Metabolic Rate is Lower in Women than in Men. Journal of Applied Physiology. 1993.
5. Westerterp KR et al. Diet Induced Thermogenesis. Physiology & Behavior. 2008.
6. Lundgren JR et al. Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined. Obesity. 2021.
7. Dahl D et al. Thyroid Function During GLP-1 Receptor Agonist Treatment. Thyroid. 2023.
8. Jastreboff AM et al. Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine. 2022.
9. Davies MJ et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. New England Journal of Medicine. 2021.
10. Rosenbaum M et al. Long-term Persistence of Adaptive Thermogenesis in Subjects Who Have Maintained a Reduced Body Weight. American Journal of Clinical Nutrition. 2008.
11. Müller MJ et al. Metabolic Adaptation to Caloric Restriction and Subsequent Refeeding. American Journal of Clinical Nutrition. 2015.

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Platform Disclaimer. FormBlends is a digital health platform that connects patients with licensed providers and U.S.-based pharmacies. We do not manufacture, prescribe, or dispense medication directly. All clinical decisions are made by independent licensed providers.

Compounded Medication Notice. Compounded semaglutide and tirzepatide are not FDA-approved. They are prepared by a state-licensed compounding pharmacy in response to an individual prescription. Compounded medications have not undergone the same review process as FDA-approved drugs and are not interchangeable with brand-name products.

Results Disclaimer. Individual results vary. Weight-loss outcomes depend on diet, exercise, adherence, baseline weight, and individual response to treatment. Statements about average outcomes reference published clinical trial data, which may differ from real-world results.

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