Oral medications for diabetes (and what about supplements?)

In brief

• Tablets are added when lifestyle change alone isn’t enough, and all of them work better alongside it.
• Metformin is the usual first medication; taking it with meals reduces stomach upset.
• SGLT2 inhibitors also protect the heart and kidneys, so we often add them early.
• Sulfonylureas can cause low blood sugar, so always carry a quick sugar source such as three sweets.
• Pause SGLT2 inhibitors if you are seriously unwell, and seek urgent care for vomiting, deep rapid breathing or severe abdominal pain.
• Supplements have weak evidence, and taking one instead of prescribed medication can be harmful.

We prescribe and adjust diabetes medication at our Punggol clinic. See our chronic disease care.

Diabetes series: 1. What is diabetes · 2. Diet and lifestyle · 3. Oral medications · 4. Injectables · 5. Preventive care

The short version

When lifestyle change alone isn’t enough, we add medication. This is not a failure. Lifestyle change doesn’t stop when medication starts, and every medication below works better alongside it.

Diabetes medication choices have expanded hugely in the last 15 years. Some classes now also reduce the risk of heart attack, stroke and kidney failure.

Metformin — the first-line drug for most adults

For most people with Type 2 diabetes, metformin is the first medication prescribed. It is cheap, safe and effective, with decades of evidence.

How it works: it mainly makes the liver release less stored glucose, and makes cells a little more sensitive to insulin. It doesn’t push the pancreas to make more insulin, so on its own it almost never causes low blood sugar.

HbA1c reduction: typically 1 to 1.5%.

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

What to watch for:

• Stomach side effects usually settle after the first few weeks. If they don’t, tell us; we can switch you to XR.
• Vitamin B12 deficiency can occur after years of use. It is worth checking if you develop anaemia, numb or tingling feet, or unexplained tiredness. On long-term metformin, we usually check B12 at least every few years.
• Lactic acidosis is rare but serious. It occurs in severe kidney or liver disease, heart failure or critical illness. So we monitor kidney function and hold metformin during hospital admissions and acute illness. For scans with contrast (dye), most people can keep taking it. It is paused if kidney function is very low or has suddenly worsened, or for some procedures that inject dye into an artery; follow the radiology team’s instructions.

Don’t stop metformin without talking to us. Getting past the early stomach upset is usually worth it.

SGLT2 inhibitors — the newer workhorses

SGLT2 (sodium-glucose cotransporter-2) inhibitors stop the kidneys reabsorbing glucose, so excess glucose passes 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 alone, but often enough with metformin.

Why we often use them early: in large trials they reduced heart failure admissions and cardiovascular deaths, and slowed chronic kidney disease. They are now recommended as an early add-on, not just third-line, for many people, especially those with heart disease, kidney disease or heart failure.

Other advantages: small weight loss (1 to 3 kg), a mild fall in blood pressure, and no hypos on their own.

What to watch for:

• Genital yeast infections: more common, especially in women. Keep up good hygiene and treat thrush early.
• Urinary tract infections: slightly more common.
• Dehydration and low blood pressure: drink enough. If you take a diuretic (“water tablet”), we may adjust doses.
• Diabetic ketoacidosis (DKA): rare but serious, even when blood sugar looks normal. 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 was seen with canagliflozin in one trial. Check your feet daily and treat any wound early.
• Sick-day rules: temporarily stop SGLT2 inhibitors if you are seriously unwell (vomiting, not eating, dehydrated, admitted to hospital or having major surgery). Restart once you are eating and drinking normally. Ask us if unsure.

GLP-1 receptor agonists — oral and injectable

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

Most are injected, usually once a week: semaglutide (Ozempic), dulaglutide (Trulicity), tirzepatide (Mounjaro, actually a GLP-1/GIP dual agonist) and liraglutide (Victoza). These are covered in Injectables — insulin and GLP-1 medications. Oral semaglutide is covered here.

Oral semaglutide (Rybelsus)

The same molecule as Ozempic, in a tablet absorbed through the stomach lining. It starts at 3 mg daily, increasing to 7 mg or 14 mg, the tablet strengths registered in Singapore. Some other countries use a newer tablet with different strengths, so always take the dose on your label.

How to take it. Rybelsus is fussy about absorption:

• Take it first thing in the morning, on an empty stomach.
• Swallow it 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. Waiting longer improves absorption.
• Don’t crush, split or chew the tablet.

Taken with food or close to other medicines, absorption drops sharply 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 and stay hydrated. Tell us if it doesn’t improve.
• Reduced appetite and modest weight loss: usually welcome.
• Pancreatitis (rare): stop and contact us urgently if you develop severe upper-abdominal pain spreading to the back, with nausea and vomiting.
• Delayed stomach emptying: may affect absorption of other medicines, and matters before surgery or anaesthesia.

DPP-4 inhibitors — the quiet ones

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

• Sitagliptin (Januvia): 25, 50 or 100 mg once daily, depending on kidney function
• Linagliptin (Trajenta): 5 mg once daily, with no dose adjustment needed in kidney disease, so a common choice in older patients
• Vildagliptin (Galvus): 50 mg once or twice daily
• Saxagliptin (Onglyza) and alogliptin (Nesina): used less. These two have shown a small heart-failure signal, so we generally avoid them if you have heart failure.

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

What to watch for: usually very little. Rarely, joint pain, skin reactions or pancreatitis; stop and tell us if you have 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 can cause low blood sugar (hypos) and weight gain.

In Singapore we mainly use these 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 chlorpropamide, an older first-generation drug, and glibenclamide, a longer-acting second-generation drug, because they cause more hypos, especially in older people.

HbA1c reduction: 1 to 1.5%.

What to watch for:

• Low blood sugar (hypoglycaemia) is the main concern. Symptoms include shakiness, sweating, hunger, headache, irritability and confusion. The risk rises if you skip meals, drink alcohol without food, exercise more than usual or have kidney problems. Always carry a quick carbohydrate, such as three sweets or half a can of regular soft drink.
• Weight gain: most people gain 2 to 4 kg.
• Driving: be aware of hypo risk. Check your sugar before driving if you have been fasting or exercising.

SGLT2 inhibitors or GLP-1s are often replacing sulfonylureas in people with heart or kidney concerns. But sulfonylureas remain a good, cost-effective option for many people.

Thiazolidinediones (pioglitazone)

Now used less often, pioglitazone (Actos) makes cells more sensitive to insulin and has shown some cardiovascular benefit in specific groups. Downsides are weight gain, fluid retention (ankle swelling) and a small increase in fracture risk. It is not suitable if you have heart failure. The full effect takes 6 to 12 weeks.

Alpha-glucosidase inhibitors (acarbose)

Acarbose (Glucobay) slows carbohydrate absorption in the gut, reducing the glucose spike after meals. Take it with the first bite of each meal, three times a day. The effect is modest (HbA1c drop of 0.5 to 0.8%). Undigested carbohydrate ferments in the gut, so the main side effects are wind, bloating and loose stools. Starting low and building up helps. It is most useful when after-meal spikes are the main problem.

Fixed-dose combinations

Some tablets combine two drugs, for example:

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

They mean fewer tablets and can help you stay on treatment, but they are less flexible to adjust. We usually start the two drugs separately, then switch to a combined tablet once the doses are settled.

What about supplements?

This comes up at almost every new-diagnosis visit. The evidence for diabetes supplements is generally weak, and some interfere with prescribed medications.

Bitter gourd (karela, momordica charantia)

Used in many Asian cuisines, with modest glucose lowering in some small studies. Eating it as food is fine and probably healthy. Concentrated supplements are not well studied and can add to hypo risk with sulfonylureas or insulin.

Cinnamon

Widely marketed, but the human evidence is weak and inconsistent. It is not a replacement for prescribed medication. Cinnamon in cooking is harmless; high-dose supplements raise liver toxicity (hepatotoxicity) concerns.

Berberine

A plant compound promoted online as “natural metformin”. Some small studies show modest benefit. But supplement quality and purity vary enormously, long-term safety is not established, and it interacts with many prescription medicines. We generally don’t recommend it.

Fenugreek, chromium, alpha-lipoic acid, vanadium

Small studies with inconsistent results, rarely to the quality standards we would want. Food amounts are harmless; concentrated supplements are a different story.

A general principle

If a supplement 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.

The real harm comes from skipping prescribed medication because you take a supplement. That leads to hospital admissions with very high blood sugar and preventable complications.

If you take, or are thinking of taking, any supplement, tell us and bring the bottle. We would rather discuss it openly.

A word on “miracle cures”

Social media, WhatsApp forwards and some providers promote injections, drips or herbal mixtures claimed to “cure” Type 2 diabetes. Some have caused real harm: liver failure, kidney injury and severe hypoglycaemia. If it sounds too good to be true, it usually is. Please talk to us before trying anything marketed this way.

When oral medications aren’t enough

For many people, one or two tablets reach the HbA1c target. For others, diabetes progresses and the next step may be:

• Adding an injectable GLP-1
• Starting basal insulin
• Or a combination

Starting insulin is not a failure. Over time, the pancreas in Type 2 diabetes naturally makes less insulin, and insulin is then the right tool. Read on:

→ Injectables — insulin and GLP-1 medications

Get in touch

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

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

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.
• American College of Radiology (ACR) Committee on Drugs and Contrast Media. ACR Manual on Contrast Media — Metformin chapter. 2024. acr.org
• National Drug Formulary, Singapore. Semaglutide — products registered with HSA. Updated September 2026. ndf.gov.sg
• European Medicines Agency. Rybelsus (semaglutide tablets): summary of product characteristics. ema.europa.eu
• Sola D, et al. Sulfonylureas and their use in clinical practice. Archives of Medical Science 2015;11(4):840–848. pmc.ncbi.nlm.nih.gov

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. v1.1 · October 2026 (v1.0 April 2026) · Review due April 2028.