Antidiabetic Drugs
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Direct answer
Metformin has held first-line status for type 2 diabetes for decades because it lowers glucose without weight gain or hypoglycaemia, acting through AMPK activation and reduced hepatic glucose output; its only feared complication, lactic acidosis, is avoided by withholding it when the estimated GFR falls below 30 mL/min, perioperatively, and in decompensated cardiorespiratory illness. Sulfonylureas close the pancreatic ATP-sensitive potassium channel and risk hypoglycaemia and weight gain; SGLT2 inhibitors spill glucose into urine delivering heart and kidney protection with a unique euglycaemic ketoacidosis risk; GLP-1 receptor agonists add weight loss at the cost of nausea. Insulin remains the only option in type 1 diabetes, with onset times that examiners expect verbatim: rapid analogues around 15 minutes, soluble regular at 30, NPH peaking at 6 to 8 hours, and glargine lasting about 24 without a peak.
What you must remember
- Diagnostic numbers: HbA1c 6.5 per cent or more, fasting plasma glucose 126 mg/dL or more, two-hour OGTT or random plasma glucose 200 mg/dL or more with symptoms.
- Metformin: holds in eGFR below 30, suspend 48 hours after iodinated contrast in renal impairment; causes vitamin B12 deficiency with long-term use; the extended-release form improves gastrointestinal tolerance; safe in pregnancy guidelines today.
- Sulfonylureas: glibenclamide causes the worst hypoglycaemia in the elderly; chlorpropamide adds SIADH and a disulfiram-like reaction; all cause weight gain.
- SGLT2 inhibitors (dapagliflozin, empagliflozin): genital mycotic infection and urinary infection, volume depletion, euglycaemic diabetic ketoacidosis (hold three days before surgery), rare Fournier gangrene, and cardiovascular-renal benefit independent of glucose.
- GLP-1 receptor agonists (semaglutide, liraglutide): weight loss and nausea; gallbladder disease and pancreatitis warnings; contraindicated in personal or family medullary thyroid carcinoma or MEN2.
- DPP-4 inhibitors (sitagliptin): weight-neutral, nasopharyngitis and arthralgia; dose-adjusted in renal impairment; no hypoglycaemia as monotherapy.
- Insulin storage, an Indian practical favourite: unopened pens or vials refrigerated at 2–8 °C; the in-use pen kept at room temperature for up to 28 days; rotate injection sites to avoid lipohypertrophy.
- Hypoglycaemia (below 70 mg/dL): the rule of 15 — 15 g fast-acting carbohydrate, recheck in 15 minutes; unconscious patient gets intravenous dextrose or intramuscular glucagon 1 mg, never oral feeding.
- Pioglitazone is contraindicated in heart failure (fluid retention) and carries fracture and bladder-caution signals.
A typical exam case: diabetic ketoacidosis
A 20-year-old presents drowsy with glucose 480 mg/dL, pH 7.10, ketones strongly positive, potassium 3.0 mmol/L. The examiner's ordered sequence: begin isotonic saline — the fluid deficit of several litres is the immediate killer — and correct the potassium before or with the insulin infusion, because insulin drives potassium into cells and a starting level of 3.0 means insulin without potassium can precipitate fatal arrhythmia. Only then starts the regular insulin infusion at 0.1 units/kg/hour. When glucose falls below about 200 mg/dL, add dextrose to the fluids and continue the insulin until ketoacidosis clears — stopping insulin because the glucose normalised is the classic error, since ketogenesis outlives glycaemia. Bicarbonate is reserved for pH below 6.9. Hunt the precipitant: in this teenager, omitted insulin during an exam-season illness is the usual story; in an older patient, infection or infarction.
Contrast the ward round question: the same sugar levels in a type 2 patient on glibenclamide with confusion at 3 a.m. is sulfonylurea hypoglycaemia — a long-acting drug in an elderly kidney is an admission in itself, treated with dextrose and observation for recurrent dips, not a sandwich and discharge.
Where students slip
Blaming metformin for hypoglycaemia in a patient also on glibenclamide is the most frequent attribution error; metformin monotherapy does not cause it. The second is missing SGLT2-associated ketoacidosis because the glucose reads "only 180 mg/dL" — the euglycaemia is precisely the trap, and ketones must be checked. Third, the insulin-storage and mixing questions: glargine cannot be mixed with other insulins in the same syringe, and mixing short with NPH alters their kinetics. Finally, writing "diet, exercise and tablets" for a thin, ketotic young patient delays lifesaving insulin — phenotypic type 1 in a lean Indian adolescent is common enough that the default must be insulin until the picture clarifies.
Frequently asked questions
What is the first-line oral drug for type 2 diabetes and its main contraindications?
Metformin, withheld when eGFR is below 30 mL/min, in decompensated heart or respiratory failure, and perioperatively to avoid lactic acidosis.
Why must potassium be checked before the insulin infusion in DKA?
Insulin shifts potassium intracellularly; a level below about 3.3 mmol/L must be replaced first, or fatal arrhythmia follows.
Which oral agents cause hypoglycaemia and weight gain?
Sulfonylureas, worst with glibenclamide in the elderly and in renal impairment; metformin, DPP-4 inhibitors and SGLT2 inhibitors do not cause hypoglycaemia as monotherapy.
What is the unique ketoacidosis risk of SGLT2 inhibitors?
Euglycaemic diabetic ketoacidosis — glucosuria lowers insulin and raises glucagon despite near-normal glucose, so ketones rise while the meter looks reassuring.
How is unopened insulin stored in the Indian household?
Refrigerated between 2 and 8 °C, never frozen; the pen in use stays at cool room temperature for up to 28 days, away from sunlight and stove heat.
Which antidiabetic drug class needs avoidance in medullary thyroid carcinoma history?
GLP-1 receptor agonists such as semaglutide and liraglutide, owing to rodent C-cell tumour signals and MEN2/MTC contraindications.