# Oral Hypoglycaemic Agents

> Oral hypoglycaemic agents for MBBS Pharmacology — classes, mechanisms, adverse effects and exam high-yield revision points.

- Canonical URL: https://prepelephant.com/topics/mbbs/pharmacology/oral-hypoglycaemic-agents
- Exam / course: MBBS · Subject: Pharmacology
- Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team
- First published: 2026-10-02
- Last updated: 2026-10-02
- How to cite: "Oral Hypoglycaemic Agents", PrepElephant, https://prepelephant.com/topics/mbbs/pharmacology/oral-hypoglycaemic-agents

## Direct answer

Oral hypoglycaemic (more precisely, antihyperglycaemic) agents lower glucose in type 2 diabetes and are classified by mechanism: insulin secretagogues (sulfonylureas and meglitinides), insulin sensitisers (metformin and thiazolidinediones), absorption delayers (alpha-glucosidase inhibitors), incretin-based drugs (GLP-1 receptor agonists and DPP-4 inhibitors) and renal glucose reabsorption blockers (SGLT2 inhibitors). Metformin plus lifestyle modification remains the foundation of first-line treatment.

## What you must remember

- Metformin (biguanide) cuts hepatic gluconeogenesis and improves insulin sensitivity through AMPK activation; it is weight-neutral, causes no hypoglycaemia alone, and is first-line — its hazards are gastrointestinal upset, vitamin B12 deficiency with long use and lactic acidosis in renal or hepatic failure; withhold it around iodinated contrast in renal impairment.
- Sulfonylureas (glibenclamide, glipizide, gliclazide, glimepiride) close the beta-cell K-ATP channel, forcing insulin release independent of glucose; hypoglycaemia — especially with long-acting glibenclamide in the elderly — and weight gain limit them; the short-acting meglitinide repaglinide works similarly but targets postprandial spikes.
- Thiazolidinediones (pioglitazone), PPAR-gamma agonists, improve peripheral insulin sensitivity but cause fluid retention and weight gain, are contraindicated in heart failure, and carry cautions for fractures and bladder cancer.
- Alpha-glucosidase inhibitors (acarbose, voglibose) delay starch and disaccharide digestion in the gut, lowering postprandial glucose at the cost of flatulence and diarrhoea; hypoglycaemia under acarbose must be treated with glucose, not sucrose.
- GLP-1 receptor agonists (subcutaneous or oral semaglutide, liraglutide, exenatide) enhance glucose-dependent insulin secretion and aid weight loss, with cardiovascular benefit; nausea, vomiting and pancreatitis risk limit use.
- DPP-4 inhibitors (sitagliptin, vildagliptin) prolong endogenous incretin action; they are weight-neutral and well tolerated, with renal dose adjustment for most.
- SGLT2 inhibitors (dapagliflozin, empagliflozin) cause glycosuria with modest weight loss and protect the heart and kidneys; hazards are genital mycotic and urinary infections, volume depletion and euglycaemic ketoacidosis, so they are paused around surgery and acute illness.
- Choice in practice: add SGLT2 inhibitors when heart failure or chronic kidney disease coexists, GLP-1 agonists when obesity or atherosclerotic disease dominates, and insulin when catabolic features appear.

## Common confusion

The recurring confusion is hypoglycaemia potential. Only the secretagogues — sulfonylureas and meglitinides — can cause hypoglycaemia, because they push insulin out regardless of glucose; metformin, SGLT2 inhibitors, alpha-glucosidase inhibitors and incretin drugs lower glucose only when it is high. A second slip is metformin's mechanism: it restrains hepatic glucose output without stimulating insulin secretion.

## Exam-focused takeaway

Theory answers should classify the drugs with mechanism, one use and one adverse effect each, then justify metformin as first line and outline add-on choices by comorbidity. Viva examiners ask why sulfonylureas cause weight gain and why metformin causes lactic acidosis. MCQs repeatedly test acarbose-related flatulence, SGLT2 inhibitor genital infections and euglycaemic ketoacidosis, sulfonylurea hypoglycaemia in the elderly and glucose (not sucrose) for hypoglycaemia under acarbose.

## Frequently asked questions

### Which oral agent is first-line in type 2 diabetes and why?

Metformin with lifestyle measures — durable efficacy, weight neutrality, no hypoglycaemia and a long safety record.

### Do sulfonylureas cause hypoglycaemia?

Yes; by closing K-ATP channels they release insulin irrespective of glucose, and glibenclamide poses the greatest risk in older patients.

### Which antidiabetic drugs help weight loss?

GLP-1 receptor agonists most, SGLT2 inhibitors modestly; metformin is weight-neutral.

### What are the characteristic adverse effects of SGLT2 inhibitors?

Genital mycotic infections, urinary tract infection, volume depletion and euglycaemic diabetic ketoacidosis.

### Which class causes flatulence and why?

Alpha-glucosidase inhibitors such as acarbose, because undigested carbohydrates are fermented in the colon.