Sulfonylureas — patient guide

This page covers the sulfonylurea family of diabetes tablets — gliclazide (Diamicron, Diamicron MR, Glyade), glimepiride (Amaryl), glibenclamide (Daonil), and glipizide (Minidiab) — and the combination tablet Glucovance. If your tablet name is on the list below, this is your page.

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You’ve arrived here for one of a few reasons. Your GP added a sulfonylurea to your diabetes plan and the explanation was brief. You’ve been on one for years and want a refresher on the things that matter — particularly the hypo question. You’ve had a low blood sugar episode that frightened you and you’re trying to work out how worried to be. Or you’ve heard from a friend or a podcast that this class is “older” and you’re wondering whether your current plan still makes sense.

All four are reasonable places to be standing. Let me give you the longer version of the conversation — what these medicines do, what to plan around, and where the integrative work fits alongside the script.

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Find your medicine

Generic name	Common brand names	Strengths	How often
Gliclazide (immediate release)	Diamicron, Glyade, generics	80 mg	Once or twice daily with meals
Gliclazide (modified release / MR)	Diamicron MR, Glyade MR, generics	30 / 60 mg	Once daily with breakfast
Glimepiride	Amaryl, Aylide, Diapride, generics	1 / 2 / 3 / 4 mg	Once daily with breakfast
Glibenclamide	Daonil, Euglucon, generics	5 mg	Once or twice daily with meals
Glipizide	Minidiab	5 mg	Once or twice daily, 30 minutes before food

A note on which sulfonylurea you’re on. In current Australian practice, gliclazide (particularly the MR form) is the most commonly initiated and the most commonly continued. Glimepiride is also common. Glibenclamide and glipizide are prescribed less often than they were a decade ago — if you’re on either, that doesn’t mean anything needs to change; it’s just useful context.

Combination tablet: Glucovance contains glibenclamide plus metformin in one tablet. Everything on this page applies to the sulfonylurea (glibenclamide) portion; the metformin page covers the other half.

Closely related families worth knowing exist — metformin (the usual first oral medicine), SGLT2 inhibitors (names end in -flozin), GLP-1 receptor agonists (Ozempic, Trulicity, Mounjaro), DPP-4 inhibitors (names end in -gliptin), and insulin. Many people end up on a sulfonylurea plus one or more of these. Each has its own page or will soon.

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What it treats

Sulfonylureas are oral medicines for type 2 diabetes — usually added when metformin alone isn’t reaching the glucose target, or used when metformin isn’t tolerated. The class has been in clinical use for more than 50 years and is well-studied. Modern AU guidance — RACGP T2DM guidelines, eTG, and NICE NG28 — positions sulfonylureas as one of several second-line options after metformin, with the choice between sulfonylurea, SGLT2 inhibitor, GLP-1 receptor agonist, and DPP-4 inhibitor made on an individual basis.

There are no off-label uses worth covering for a patient flyer. All AU sulfonylurea use is for type 2 diabetes.

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The basics

1. Meal first, tablet second. Take your sulfonylurea with a meal that contains carbohydrate. If a meal is going to be delayed or skipped, delay or skip the tablet to match (and message us if it happens often).
2. Carry fast-acting carb at all times. Jellybeans, glucose gel, or a small juice box. Use the 15-15 rule if symptoms suggest a low blood sugar: 15 g fast carb, recheck in 15 minutes.
3. Know the symptoms of a hypo. Sweating, shakiness, hunger, dizziness, irritability, blurred vision, confusion. Severe episodes can involve loss of consciousness or seizure — that’s an ambulance call.
4. Have a sick day plan written down before you need it — see the section below.
5. Tell us or your pharmacist before starting any new medicine — including short antibiotic courses, antifungals, and over-the-counter medicines. Several common ones change how your sulfonylurea behaves.

Everything else — how it works, side effects in detail, the integrative angle, the conversation about lower-risk lifestyle — is below.

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What to expect in the first month

Week 1

• Your prescriber will usually start at the lower end of the dose range — for gliclazide MR, that’s 30 mg with breakfast.
• Take it with food. Carbohydrate matters more than fat or protein for matching the medicine’s effect.
• You won’t usually “feel” anything different. The change shows up on blood glucose readings and on HbA1c over weeks.

Weeks 2-3

• If you have a home glucose meter, the prescriber may ask you to check fasting and 2-hours-post-meal a few times a week so we have data for the next conversation.
• Watch for any low-blood-sugar symptoms, particularly in the late morning (a few hours after the breakfast dose) or in the late afternoon if you’re on a twice-daily regimen.

Weeks 4-12

• Dose may be titrated up depending on glucose response and tolerance.
• First HbA1c recheck is usually around 3 months.
• Weight tracking — modest weight gain is common in the first 6 months; the lifestyle work below is the lever for this.

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Sick day rules — when to pause

If you have any of the following for more than a few hours, pause the sulfonylurea and message us:

• Vomiting
• Severe diarrhoea
• Fever where you can’t keep fluids or food down
• Any acute serious illness — chest infection requiring hospital, suspected sepsis, severe pain
• Planned fasting for surgery or a procedure (we plan this in advance with you)

Restart once you’re eating and drinking normally again and feel well — usually 24-48 hours. If you’re not sure, message.

The reason: when you’re not eating, the dose that was perfectly safe with a normal meal becomes a hypo risk. Pausing the tablet during a gastro illness is not “stopping the medicine” — it’s part of normal use. The serious version of not pausing is a severe hypoglycaemic episode requiring an ambulance, and the Gangji systematic review (Diabetes Care 2007) is the literature behind why we take this rule seriously.

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Tap any section below to expand the detail.

How does it work?

Sulfonylureas bind a specific receptor on the pancreatic beta cell — the SUR1 subunit of an ATP-sensitive potassium channel. Closing that channel triggers the cell to release stored insulin. Unlike metformin, which works mainly on the liver and on muscle insulin sensitivity, sulfonylureas push more insulin into the bloodstream from your own pancreas. That’s why they can cause low blood sugar even when you haven’t eaten — the insulin is being released regardless of meal timing.

The class has been in continuous clinical use since the 1950s. The original concern about cardiovascular risk came from the UGDP study in the 1970s, which tested tolbutamide (an early sulfonylurea no longer marketed in Australia) and raised a mortality signal. That signal has not been replicated in modern sulfonylureas. The ADVANCE trial (NEJM 2008) followed more than 11,000 patients on gliclazide-MR-based intensive glucose-lowering and supported cardiovascular neutrality. The CAROLINA trial (JAMA 2019) compared glimepiride directly against linagliptin (a DPP-4 inhibitor) over a median of ~6 years in T2DM patients with high cardiovascular risk — also cardiovascular-neutral, with higher hypoglycaemia and modest weight gain in the glimepiride arm.

Two things fall out of this evidence. First — the cardiovascular concern from the 1970s does not transfer to the gliclazide or glimepiride being prescribed today. Second — the trade-offs of the class (hypoglycaemia, weight) are real and quantified, not theoretical. Both can be held at the same time.

Side effects in detail

Common

• Hypoglycaemia (low blood sugar). The dominant side effect of the class. Symptoms come in two layers: an early adrenergic layer (sweating, shakiness, hunger, palpitations, tremor) and a later neuroglycopenic layer (dizziness, confusion, blurred vision, difficulty speaking, drowsiness). Treatment is the 15-15 rule: 15 g of fast-acting carbohydrate (jellybeans, glucose gel, half a small juice box, three teaspoons of sugar in water), recheck in 15 minutes, repeat if still low, then a longer-acting snack if a meal isn’t due within an hour. Severe episodes — loss of consciousness, seizure, inability to swallow — require an ambulance and IV glucose or glucagon. Australian Diabetes Educators Association has plain-English resources. Within the class, glibenclamide has the strongest hypoglycaemia signal (long half-life, active metabolite), gliclazide MR the lowest.
• Modest weight gain. Typically 2-5 kg over the first 6-12 months, most of it in the first 6 months. The mechanism is the same as the glucose-lowering effect — insulin is the body’s main fuel-storage hormone. Confirmed in CAROLINA. Lifestyle work meaningfully softens the trajectory.

Less common but worth knowing

• Skin rash, itching. Usually mild; can be early hypersensitivity. Discuss with the prescriber promptly if it appears.
• Photosensitivity. Rare; sun-exposed areas reacting more than expected. Standard sun-protection.
• Hyponatraemia (low sodium). Reported particularly with higher-dose glimepiride. Symptoms — new confusion, fatigue, nausea, seizure — warrant a sodium check.
• Mild liver enzyme rise. Uncommon; usually picked up on routine bloods.

Rare but serious — get reviewed urgently

• Severe hypoglycaemia with impaired consciousness or seizure. Call 000.
• Unexplained jaundice (yellow skin or eyes), dark urine, severe upper-abdominal pain. Suggests a hepatic reaction; needs urgent review.
• Acute haemolysis in G6PD deficiency. Rare but documented — sudden fatigue, pallor, dark urine.

Drugs, food, and alcohol

Tell us or your pharmacist before combining with:

• Fluconazole and other azole antifungals. Block CYP2C9 (the liver enzyme that clears sulfonylureas), raising blood levels and the hypoglycaemia risk. Single-dose fluconazole for thrush is usually manageable; longer courses warrant a dose conversation.
• Amiodarone. Cardiac rhythm medicine; inhibits CYP2C9. Monitor for low blood sugar after starting.
• Warfarin. Two-way interaction — both INR and glucose levels can move. Closer monitoring during dose changes.
• Trimethoprim and co-trimoxazole (Bactrim). Potentiate hypoglycaemia, particularly in older adults and in renal impairment.
• Beta-blockers (metoprolol, bisoprolol, propranolol, atenolol). Can mask the adrenergic warning symptoms of a hypo (tremor, palpitations). Sweating is usually still preserved. Rely more on glucose checks and less on symptoms if you’re on both.
• ACE inhibitors and ARBs. Small case-report signal of enhanced hypoglycaemia; clinically modest. No routine dose change.
• NSAIDs (ibuprofen, naproxen). Minor protein-binding interaction; usually not clinically significant for short courses.
• Other diabetes medicines. Combinations with metformin, DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 receptor agonists, and insulin are all routine. Hypoglycaemia risk rises particularly when sulfonylurea is added to insulin or to a GLP-1 agonist — dose adjustment is the prescriber’s call.

Food. Take the tablet with a meal containing carbohydrate. Same principle on weekends as on weekdays. Bigger meals tolerate a slightly later tablet; smaller meals or skipped meals raise the hypo risk.

Alcohol. Light to moderate amounts with food are usually fine. The risks concentrate in three situations: heavy or binge drinking (impairs the liver’s ability to release stored glucose, particularly overnight), drinking on an empty stomach (same mechanism, faster), and the delayed hypo that can arrive 6-12 hours after the drink (often during sleep). If you choose to drink, do it with food, stay within Australian Alcohol Guidelines, and check your blood glucose before bed after more than one or two standard drinks.

Generic substitution at the pharmacy. Generic gliclazide, glimepiride, glibenclamide, and glipizide are bioequivalent to the branded versions and work the same. The one swap worth flagging: gliclazide IR to gliclazide MR is not a like-for-like change — same active ingredient, different release profile, different dosing pattern. If your pharmacist offers that swap, confirm with us first.

Driving and machinery

Sulfonylureas are one of the diabetes medicine classes specifically flagged in the Austroads “Assessing Fitness to Drive” standards because of the hypoglycaemia risk.

Private vehicle drivers should:

• Check blood glucose before driving if there is any reason to suspect it might be low.
• Carry fast-acting carbohydrate in the car.
• Stop driving immediately if hypoglycaemic symptoms appear, treat the hypo, and wait 45 minutes after blood glucose normalises before driving again.

Commercial vehicle drivers (taxi, heavy vehicle, public passenger) face stricter requirements:

• Regular glucose self-monitoring as part of the fitness-to-drive assessment.
• Disclosure to the driver-licensing authority.
• More conservative thresholds for when driving is permissible after a hypoglycaemic episode.

If your work involves driving for a living, raise this explicitly at your next review — we’ll go through the current Austroads wording together and document the plan.

Monitoring — what blood tests and when

• Baseline before starting: eGFR (kidney function), HbA1c, fasting glucose, liver function, full blood count.
• HbA1c every 3 months until on a stable dose with a stable result, then every 6 months.
• eGFR at least annually — sooner if you have CKD, have started a new kidney-relevant medicine, or have been acutely unwell. Worsening kidney function is the most common reason to adjust or switch a sulfonylurea.
• Liver function as clinically indicated.
• Sodium if you develop new confusion, fatigue, or any other symptom that could fit hyponatraemia, particularly on higher-dose glimepiride.
• Home blood glucose as agreed at the consult — typically a structured week of fasting plus 2-hours-post-meal readings periodically, plus any time you feel symptoms suggesting a hypo.

Message us if you: start a new medicine (including over-the-counter or short antibiotic courses), develop a gastro illness, make a significant diet change, plan surgery or a long trip with disrupted meals, or have a hypoglycaemic episode that needed treatment.

Stopping or pausing

Don’t stop on your own without talking to us first — but pausing for sick days is normal use, not stopping.

• Sick day pauses (above) — 24-48 hours during gastro, severe illness, or planned fasting for procedures. Resume when eating and drinking and well.
• If hypoglycaemia is the issue, we usually adjust the dose or switch within the class (often toward gliclazide MR if not already on it) before moving to a different drug family entirely.
• If weight gain is the dominant concern, discuss alternatives — the newer classes have different weight profiles.
• If your situation changes — substantial weight loss, improved HbA1c on lifestyle, treatment of sleep apnoea, change in kidney function — the dose may genuinely come down. Done together, with monitoring.
• Before surgery, the surgical and anaesthetic team will usually ask you to hold the dose during fasting and restart when you’re eating again. Tell them you’re on a sulfonylurea.

Pregnancy and breastfeeding

Sulfonylureas in pregnancy are a relative contraindication. Current AU practice — guided by ADIPS and RANZCOG — favours metformin and insulin over sulfonylureas for gestational diabetes. Glibenclamide was historically used in GDM; that role has largely been taken over by the metformin-plus-insulin combination.

Pre-conception planning. If you are planning pregnancy or have just found out, message us early. The medicine question is planned case-by-case with your obstetric team and your GP — not by self-cessation, not from a page. Stopping a glucose-lowering medicine abruptly can destabilise glycaemic control, which carries its own pregnancy risks.

Breastfeeding. Limited safety data for sulfonylureas in breastfeeding. Decision is individualised — discuss with us and with the obstetric team.

TGA pregnancy categories vary across the class (typically C). The categories are an input to the decision, not the decision itself.

If you’re on Glucovance (sulfonylurea plus metformin)

Glucovance is one tablet containing both glibenclamide (the sulfonylurea) and metformin. It used to be a more common prescription; in current AU practice many prescribers prefer to dispense the two medicines separately so each can be titrated independently — and many prefer gliclazide over glibenclamide when a sulfonylurea is needed.

If you’re on Glucovance, everything on this page applies to the glibenclamide portion. The metformin page covers the other half — including the B12 monitoring, sick day rules for metformin specifically, and the lactic acidosis discussion. The two sets of sick-day rules overlap (pause both during gastro, severe illness, before contrast scans, before major surgery) but the reasons are different.

If you’d prefer to discuss whether the combination tablet is still the right format for you, raise it at the next review. Splitting into separate tablets, or switching the sulfonylurea component to gliclazide, is a common practical adjustment.

Cost

Sulfonylureas are listed on the PBS and are among the most affordable diabetes medicines available. From 1 January 2026, the PBS co-payment ceiling is:

• General patient: up to $25.00 per script
• Concession card holder: up to $7.70 per script

Generic gliclazide, glimepiride, glibenclamide, and glipizide often price under the general co-payment threshold (“under-co-payment” pricing). Branded versions (Diamicron, Diamicron MR, Amaryl, Daonil) may cost the full co-payment. Glucovance is also on the PBS. Confirm pricing with your pharmacist — they can show you the cheapest equivalent.

(MBS / PBS items verified 2026-05-25 via WebSearch — workspace egress to mbsonline.gov.au + pbs.gov.au still blocked; spot-check confirms current.)

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This is not a cop-out — it’s the reason the consult exists. You are biochemically unique. Anything I write here may apply to you completely, in part, or not at all, and there is no honest way to know in advance. Some people are allergic to peanuts; your biochemistry has its own particulars, and uncovering them is its own work — done by experimenting on yourself, with informed starting points. Everything on this page is general in nature for exactly that reason. The specific version of any of this is a conversation, not an article.

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The integrative view

Most of the patients I see want to do everything they reasonably can alongside the medicine. Type 2 diabetes is one of the conditions where that posture pays off the most — because the underlying picture (insulin resistance, visceral adiposity, sleep disruption, often untreated sleep apnoea, stress-driven cortisol patterns, ultra-processed food intake) is genuinely modifiable. The medicine works on the glucose number. The lifestyle work changes the terrain that produced the number.

Two principles I work from. First — the sulfonylurea is doing what it’s doing whether or not you change anything else, and that’s fine. Second — every meaningful change in the terrain (weight, eating pattern, movement, sleep, sleep apnoea treatment if present) tends to lower the dose the medicine needs to be at, and sometimes lets you come off entirely. Done together, with monitoring, not solo.

The hypoglycaemia surface of the class adds one specific layer: behavioural changes that lower blood glucose can also lower it too much if the medicine dose doesn’t move in step. If you genuinely change the eating pattern, drop weight, or start consistent resistance training, message us — we may need to drop the sulfonylurea dose to match. Not doing so is the most common avoidable cause of new hypoglycaemic episodes in patients who are otherwise doing everything right.

Strong evidence — these reliably improve glucose control

These are interventions where the data is solid enough to discuss with any patient on a sulfonylurea. The effect sizes below are approximations from clinical trials; individual response varies.

• DASH-style or Mediterranean-style eating pattern. Vegetables, fruit, legumes, whole grains, oily fish, olive oil, nuts. Multi-trial data showing improvements in HbA1c, blood pressure, and cardiovascular outcomes. Mediterranean pattern has particularly strong data in metabolic syndrome.
• Carbohydrate quality and timing. Less about cutting carbs entirely and more about choosing slower-absorbing versions — legumes, oats, intact whole grains, vegetables — over the fast ones (white bread, sugary drinks, refined cereals). For sulfonylureas specifically, the timing of carbohydrate matters as much as the quality: matching meal carbohydrate to tablet timing is the single most important behavioural pairing.
• Resistance training. 2-3 sessions per week. Improves insulin sensitivity per minute more than aerobic exercise. 20 minutes of weights twice a week meaningfully shifts the picture.
• Aerobic exercise. 150 minutes per week of brisk walking, cycling, or equivalent. Synergistic with resistance training. On a sulfonylurea, unusual amounts of exercise can trigger a hypo — check glucose before, carry fast-acting carb, and consider a snack before sustained exercise.
• Treating sleep apnoea if present. Sleep deprivation and untreated OSA worsen insulin resistance measurably. Snoring + daytime tiredness + observed pauses in breathing — worth a sleep study.
• Time-restricted eating windows. Emerging evidence is encouraging — an 8-10 hour eating window appears to improve glycaemic control and weight in T2DM. On a sulfonylurea, fasting protocols need to be planned with the prescriber — the standard tablet dose may need to come down to match the changed eating pattern.

Moderate evidence — likely helpful

• Magnesium-rich foods (leafy greens, nuts, seeds, legumes, dark chocolate). Adequate magnesium supports insulin signalling. Food first.
• Vitamin D adequacy. Target 75-100 nmol/L. Independent association with glycaemic control. Check level; supplement if low.
• Stress reduction practices — slow breathing (around 6 breaths per minute), meditation, yoga. Modest direct glucose effect, bigger indirect effect via cortisol and food choices.

Limited or emerging evidence

• Cinnamon, fenugreek, bitter melon, gymnema. Modest evidence, considerable individual variation. If they’re already part of your eating culture, fine. Supplement form is low-confidence for me — not actively harmful in typical doses, but not a recommendation either.
• Chromium. Cochrane review in T2DM shows minimal incremental benefit on top of standard care. Not a routine recommendation.
• Omega-3 (fish oil), 1-3 g EPA/DHA daily. Cardiovascular protection more than glucose effect.
• CoQ10, L-carnitine. Speculative mitochondrial / ageing support. No robust RCTs in T2DM specifically.

Specific to being on a sulfonylurea

• Berberine 500 mg three times daily activates AMPK and has RCT evidence in PCOS, lipids, and glycaemic control. It is not a substitute for a sulfonylurea — the outcome data isn’t comparable. Combining with a sulfonylurea raises the hypoglycaemia risk, because both lower glucose. Not safe in pregnancy. If you’re considering it, that’s the conversation we have in the consult — not a solo experiment.
• Alcohol awareness — covered above. The interaction with hypoglycaemia is the headline.
• Hypoglycaemia awareness training. Worth doing once formally. Diabetes Australia and credentialled diabetes educators offer structured sessions. Useful particularly for patients who’ve never had a hypo (low recognition of early symptoms) and for patients who’ve had several (sometimes symptom awareness fades).

When the medicine dose might come down

Three scenarios where dose reduction (or rarely, cessation) becomes a realistic conversation:

• Substantial sustained lifestyle change. Particularly meaningful weight loss, consistent resistance training, sleep apnoea treatment. As insulin sensitivity improves, the same sulfonylurea dose can start to produce hypos.
• Renal function declining. As eGFR drops, sulfonylurea clearance slows and the effective dose rises. Glibenclamide especially needs an earlier dose-down or switch.
• Adding a newer agent. When an SGLT2 inhibitor, GLP-1 receptor agonist, or insulin gets added, the sulfonylurea dose often comes down to balance hypoglycaemia risk against glycaemic target.

You always have a choice. Each choice has a consequence. The medicine is one lever; the terrain underneath it is another. Done together.

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Track these between now and your next visit

• Home blood glucose readings if you have a meter — fasting and 2-hours-post-meal, a structured week or two before each review. Bring the log.
• Any low-blood-sugar episodes — note time, severity, treatment, suspected trigger (missed meal, alcohol, unusual exercise, new medicine).
• Anything new you’ve started — supplements, herbs, big diet changes, new medicines from another doctor or specialist.
• Sick days, surgery, or fasting periods since the last visit, and whether you paused the sulfonylurea.
• Your weight, exercise routine, sleep pattern. Short notes, not a spreadsheet. The trajectory matters more than the precision.

Bring the list to your review appointment.

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This is general information, not personal medical advice. Every patient is different. Decisions about your medicines — which one, what dose, when to pause, what to combine with — are made with the doctor who prescribed them. If anything on this page appears to contradict advice from your treating doctor, follow your doctor; they have context about your situation that this page cannot.

Reading this page does not establish a doctor-patient relationship with Dr Hoebing Lo. If you are not a current patient, please discuss your medicines with your own GP, specialist, or pharmacist.

About the integrative content. The lifestyle, dietary, and complementary recommendations on this page summarise current published research. Effect sizes are approximations from clinical studies — individual response varies, and real-world results are commonly smaller than trial results because day-to-day life differs from study conditions. Supplements and herbal products are not interchangeable with prescribed medication and can interact with it. Talk to your doctor and pharmacist before starting any new supplement, herbal product, or significant change in diet.

Currency. This page reflects clinical practice as of the last-reviewed date. Medicine evolves; specific details may date between reviews. Pricing shown is indicative; confirm with your pharmacist.

No commercial relationships. Dr Hoebing Lo has no financial or commercial relationship with the manufacturer of any medicine, brand, or supplement mentioned on this page.

Emergencies. If you have a severe hypoglycaemic episode with loss of consciousness, seizure, inability to swallow, or persistent confusion — or any chest pain, sudden severe abdominal pain, severe muscle pain after acute illness, or sudden severe confusion — call 000 or go to your nearest emergency department. Do not wait, and do not message us first.