Oral medications for diabetes (and what about supplements?)

About this guide

When lifestyle change alone isn’t enough, medication is added — not as a failure, but as another tool. The good news is that the choice of diabetes medication has expanded hugely in the last 15 years, and we now have several classes of drugs that do more than just lower blood sugar — some reduce the risk of heart attack, stroke, and kidney failure on top.

Which also makes things confusing. Patients often come to us with a bag of tablets and no clear idea which is doing what. One of the most common problems we see is medication confusion — and that confusion is a barrier to good control. This guide is our attempt to make the categories clear.

This is the third of five short guides:

1. What is diabetes and pre-diabetes?
2. Diet and lifestyle for diabetes and pre-diabetes — still the foundation, including when you’re on medication
3. Oral medications for diabetes (you are here)
4. Injectables — insulin and GLP-1 medications
5. Preventive care for diabetes

Note: lifestyle change doesn’t stop when medication starts. Every medication below works better when paired with the diet and movement changes covered in Piece 2.

The short version

The rest of this guide goes through each in more detail. You probably only need to read the sections for medications you are actually taking.

Metformin — the first-line drug for most adults

For the vast majority of people with Type 2 diabetes, metformin is the first medication prescribed. Cheap, safe, effective, and decades of evidence behind it.

How it works: it mainly tells the liver to release less stored glucose. It also makes your cells a bit more sensitive to insulin. It doesn’t push the pancreas to produce more insulin, which is why metformin on its own almost never causes low blood sugars.

HbA1c reduction: typically 1 to 1.5%.

How to take it: with or just after meals — this reduces the most common side effect, which is stomach upset (nausea, loose stools, occasional vomiting). Start low (e.g. 500 mg once or twice a day) and build up over a few weeks. Extended-release versions (XR) are available and often better tolerated.

What to watch for:

• Stomach side effects — usually in the first few weeks and usually settle. Take with food. If they don’t settle, tell us — we can switch to an XR formulation.
• Vitamin B12 deficiency — can occur with long-term use (years), and is worth checking if you develop anaemia, numb or tingling feet, or unexplained tiredness. We usually check B12 levels at least once every few years if you’ve been on metformin long term.
• Lactic acidosis — a rare but serious side effect in specific situations: severe kidney disease, severe liver disease, heart failure, or critical illness. This is why we monitor kidney function and will hold metformin during hospital admissions, before contrast scans, and during acute illness.

Do not stop metformin without discussing with us. It is usually well worth the effort of getting past the initial stomach upset.

SGLT2 inhibitors — the newer workhorses

“SGLT2” stands for sodium-glucose cotransporter-2. These drugs block glucose reabsorption in the kidneys, so excess glucose is passed out in the urine.

Three are available in Singapore:

• Dapagliflozin (Forxiga) — 10 mg once daily
• Empagliflozin (Jardiance) — 10 or 25 mg once daily
• Canagliflozin (Invokana) — 100 or 300 mg once daily

HbA1c reduction: 0.6 to 0.9% (modest by itself, but often enough when combined with metformin).

Why we often reach for these early: in large clinical trials, SGLT2 inhibitors have been shown to reduce hospital admissions for heart failure, reduce cardiovascular deaths, and slow the progression of chronic kidney disease. They are now recommended as an early add-on — not just a third-line option — for many patients with diabetes, especially those with existing heart disease, kidney disease, or heart failure.

Other advantages: small weight loss (1 to 3 kg), mild blood pressure drop, and they don’t cause hypos on their own.

What to watch for:

• Genital yeast infections — more common, especially in women. Good genital hygiene and a low threshold for treating thrush early.
• Urinary tract infections — slightly more common.
• Dehydration and low blood pressure — stay well hydrated. If you’re also on a diuretic (“water tablet”), we may adjust doses.
• Diabetic ketoacidosis (DKA) — rare but serious, can happen even at normal-looking blood sugars. Call us or go to A&E urgently if you have unexplained nausea, vomiting, deep rapid breathing, fruity-smelling breath, confusion, or severe abdominal pain.
• Amputation risk — a small signal seen with canagliflozin in one trial. Check your feet daily, treat any wound early.
• Sick-day rules: temporarily stop SGLT2 inhibitors if you are seriously unwell (vomiting, not eating, dehydrated, hospital admission, major surgery). Restart when you’re back to normal eating and drinking. Ask us if unsure.

GLP-1 receptor agonists — oral and injectable

GLP-1 stands for glucagon-like peptide-1. These medicines increase insulin release from the pancreas after meals (when it’s needed), reduce appetite, slow stomach emptying, and lead to meaningful weight loss in most people.

Most GLP-1 drugs are injectables (once-weekly, in most cases). The injectable versions — semaglutide (Ozempic), dulaglutide (Trulicity), tirzepatide (Mounjaro, which is actually a GLP-1/GIP dual agonist), liraglutide (Victoza) — are covered in the next guide: Injectables — insulin and GLP-1 medications.

There is one oral GLP-1, which is covered here:

Oral semaglutide (Rybelsus)

Same molecule as injectable Ozempic, but absorbed through the stomach lining in tablet form. Dosing: 3 mg daily to start, increasing to 7 mg or 14 mg.

How to take it — this matters, because Rybelsus is fussy about absorption:

• Take it first thing in the morning, on an empty stomach.
• Swallow with a small sip of plain water — no more than about 120 ml (half a regular drinking glass).
• Wait at least 30 minutes before eating, drinking anything else, or taking other medicines. The longer the wait, the better the absorption.
• Don’t crush, split, or chew the tablet.

If Rybelsus is taken with food or close to other medicines, absorption drops significantly and it may not work.

What to watch for:

• Nausea — very common at higher doses, especially in the first few weeks. Eat smaller portions, avoid greasy food, stay hydrated. Usually improves; if not, tell us.
• Reduced appetite and modest weight loss — usually welcome.
• Rare pancreatitis — stop and contact us urgently if you develop severe upper-abdominal pain radiating to the back, with nausea and vomiting.
• Delayed stomach emptying — may affect absorption of other medicines or matter before surgery / anaesthesia.

DPP-4 inhibitors — the quiet ones

DPP-4 inhibitors work through the same incretin system as GLP-1s, but less potently. They are well tolerated, taken once a day, rarely cause hypos, and don’t cause weight change — which makes them a reasonable add-on in older or frail patients, or in those with kidney problems.

Available in Singapore include:

• Sitagliptin (Januvia) — 25, 50, or 100 mg once daily (dose depends on kidney function)
• Linagliptin (Trajenta) — 5 mg once daily — no dose adjustment needed in kidney disease, which makes it a common choice in older patients
• Vildagliptin (Galvus) — 50 mg once or twice daily
• Saxagliptin (Onglyza) and alogliptin (Nesina) — used less; a small heart-failure signal has been seen with these two, so generally avoided if you have heart failure

HbA1c reduction: 0.5 to 0.8% — modest, but every bit helps.

What to watch for: generally minimal. Rarely joint pain, skin reactions, or pancreatitis (stop and tell us if severe upper-abdominal pain).

Sulfonylureas — the older insulin pushers

Sulfonylureas push the pancreas to release more insulin. They are cheap, well-studied, and effective — but they come with two downsides that matter: low blood sugars (hypos) and weight gain.

In Singapore we use the second-generation sulfonylureas:

• Gliclazide (Diamicron) — once or twice daily; modified-release (Diamicron MR) is once daily
• Glimepiride (Amaryl) — once daily
• Glipizide — once or twice daily

We avoid older ones — chlorpropamide and glibenclamide — because they cause more hypos, especially in the elderly.

HbA1c reduction: 1 to 1.5%.

What to watch for:

• Low blood sugar (hypoglycaemia) — the main concern. Symptoms: shakiness, sweating, hunger, headache, irritability, confusion. Particularly risky if you skip meals, drink alcohol without food, exercise more than usual, or have kidney problems. Always carry a quick carbohydrate (three sweets, half a can of regular soft drink) with you if you’re on a sulfonylurea.
• Weight gain — most patients gain 2 to 4 kg.
• Driving — be aware of hypo risk. Check your sugar before driving if you’ve been fasting or exercising.

Sulfonylureas are often being replaced by SGLT2 inhibitors or GLP-1s in patients who have cardiovascular or kidney concerns — but they remain a good cost-effective option for many people.

Thiazolidinediones (pioglitazone)

Used less often now. Pioglitazone (Actos) makes cells more sensitive to insulin and has actually shown some cardiovascular benefit in specific patient groups. Downsides: weight gain, fluid retention (ankle swelling), and a small increase in fracture risk. Not suitable for patients with heart failure. Takes 6 to 12 weeks to see the full effect.

Alpha-glucosidase inhibitors (acarbose)

Acarbose (Glucobay) slows the absorption of carbohydrates in the gut, reducing the post-meal glucose spike. Taken with the first bite of each meal, three times a day. Modest effect (HbA1c drop 0.5 to 0.8%). Main side effect: wind, bloating, loose stools — because undigested carbs ferment in the gut. Often better tolerated if you start low and build up. Particularly useful for people whose post-meal glucose spikes are the main problem.

Fixed-dose combinations

You may be prescribed a tablet that combines two drugs in one — for example:

• Metformin + dapagliflozin (Xigduo XR)
• Metformin + empagliflozin (Jardiance Duo)
• Metformin + sitagliptin (Janumet)
• Metformin + linagliptin (Trajenta Duo)
• Metformin + glimepiride (Amaryl M)

These reduce the number of tablets you take each day and can help with adherence — but they’re less flexible to adjust. We usually start the two drugs separately first, then switch to a combined tablet once the doses are settled.

What about supplements?

This comes up at almost every new-diagnosis visit. The short answer:

The evidence for diabetes supplements is generally weak, and some can interfere with your prescribed medications. A few of the most common ones:

Bitter gourd (karela, momordica charantia)

Used traditionally in many Asian cuisines. Modest glucose-lowering in some small studies. If you eat bitter gourd as food, that’s fine and probably a healthy choice. Concentrated supplements are not well-studied, and can add to the hypo risk if taken with sulfonylureas or insulin.

Cinnamon

Popular and widely marketed. The human evidence is weak and inconsistent. Not a replacement for your prescribed medication. Cinnamon in cooking is harmless; high-dose concentrated supplements have hepatotoxicity concerns.

Berberine

An active compound from certain plants, promoted online as “natural metformin.” Some small studies show modest benefit, but the quality and purity of supplements vary enormously, and long-term safety is not established. Can interact with many prescription medications. We generally don’t recommend it.

Fenugreek, chromium, alpha-lipoic acid, vanadium

Small studies, inconsistent results, rarely tested at the quality standards we’d want before giving to patients. Nothing harmful in food-amounts, but concentrated supplements are a different story.

A general principle

If a supplement actually worked as well as its marketing claims, it would be standard prescribed treatment by now. The pharmaceutical industry has no reason to ignore something that worked.

What’s genuinely harmful is the idea that taking a supplement means you can skip your prescribed medication — that’s the path to hospital admissions with very high blood sugars and preventable complications.

If you’re taking (or thinking of taking) any supplement, tell us. Bring the bottle. We’d rather discuss it openly than have you skip it at your visits.

A word on “miracle cures”

Social media, WhatsApp forwards, and some private clinics occasionally promote injections, drips, or herbal mixtures that are claimed to “cure” Type 2 diabetes. Some of these have caused real harm — liver failure, kidney injury, severe hypoglycaemia. If it sounds too good to be true, it usually is. Please come and discuss with us before trying anything marketed this way.

When oral medications aren’t enough

For many patients, one or two oral tablets is enough to hit HbA1c target. For others, diabetes progresses and more is needed. The next step may be:

• Adding an injectable GLP-1 (covered in the next guide)
• Starting basal insulin (also next guide)
• Or a combination

Starting insulin is sometimes framed as a failure — it isn’t. It’s the right tool for the job when the pancreas isn’t producing enough insulin on its own anymore, which is a natural progression of Type 2 diabetes over time. Read on:

→ Injectables — insulin and GLP-1 medications

Get in touch

Joo Chiat — 172 Joo Chiat Road, #01-01, Singapore 427443 · Tel 6920 1952

Punggol — 658 Punggol East, #01-04, Singapore 820658 · Tel 6312 4589

Email — admin@ktmc.sg

References

• Agency for Care Effectiveness (ACE). Oral glucose-lowering agents in type 2 diabetes mellitus — an update. Updated August 2017. ace-hta.gov.sg
• Agency for Care Effectiveness (ACE). Initiating basal insulin in type 2 diabetes mellitus. Updated November 2024.
• American Diabetes Association. Standards of Care in Diabetes — 2026. diabetesjournals.org
• Health Sciences Authority Singapore. Drug safety advisories on SGLT2 inhibitors, DPP-4 inhibitors, and diabetes medications.

This information is for general education only and is not a substitute for medical advice. Medication choice must be individualised to your situation — please speak with our team about what’s right for you. v1.0 · April 2026 · Review due April 2028.