Oral glucose-lowering medicines are primarily used for type 2 diabetes mellitus (T2DM), where insulin resistance, progressive beta-cell dysfunction and inappropriate hepatic glucose output combine to produce hyperglycaemia. They do not replace insulin in type 1 diabetes or diabetic ketoacidosis. Choice of treatment must be individualised to kidney function, cardiovascular disease, heart failure, weight, hypoglycaemia risk, cost, pregnancy status and the patient’s ability to eat, monitor and follow up.
Learning objectives
- Relate each oral drug class to the pathophysiology of type 2 diabetes and its main glucose-lowering effect.
- Prescribe practical adult doses and titration schedules while checking renal and hepatic safety.
- Distinguish glucose-dependent from glucose-independent therapies and predict hypoglycaemia risk.
- Recognise important class-specific adverse effects: metformin-associated lactic acidosis, sulfonylurea hypoglycaemia, pioglitazone fluid retention, SGLT2-inhibitor ketoacidosis and genital infection, and incretin-associated gastrointestinal or pancreatic toxicity.
- Use an emergency approach to severe hypoglycaemia, euglycaemic ketoacidosis, metformin toxicity and dehydration.
1. Diabetes context and therapeutic targets
Diabetes mellitus is chronic hyperglycaemia caused by inadequate insulin secretion, impaired insulin action, or both. In type 1 diabetes, autoimmune beta-cell destruction creates an absolute insulin deficiency; insulin is essential and oral agents cannot substitute for it. In type 2 diabetes, hepatic glucose overproduction, skeletal-muscle insulin resistance, adipose dysfunction, impaired incretin action and progressive beta-cell failure coexist.
| Clinical question | Why it matters before choosing an oral drug |
|---|---|
| Is this type 1 diabetes, ketosis-prone diabetes or DKA? | These require insulin and urgent metabolic management; an oral agent alone is unsafe. |
| What is the kidney function? | Metformin, sulfonylureas, SGLT2 inhibitors and some DPP-4 inhibitors require renal-based decisions. |
| Is there ASCVD, heart failure or chronic kidney disease? | Prefer agents with proven cardiovascular/renal benefit when available and affordable, particularly SGLT2 inhibitors or GLP-1 receptor agonists. |
| Is avoiding hypoglycaemia a priority? | Prefer metformin, DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 receptor agonists or pioglitazone over insulin secretagogues when appropriate. |
| Is the patient pregnant, planning pregnancy or breastfeeding? | Many oral agents have limited safety data; use local obstetric/diabetes guidance and do not continue a medicine automatically. |
| Can the patient eat reliably and attend monitoring? | Meal-dependent secretagogues are hazardous when meals are skipped; complex regimens may fail without education. |
2. Classification
| Class | Examples | Principal action | Hypoglycaemia as monotherapy | Weight effect |
|---|---|---|---|---|
| Biguanide | Metformin | Reduces hepatic gluconeogenesis; improves insulin sensitivity | Low | Neutral or modest loss |
| Sulfonylureas | Gliclazide, glimepiride, glipizide, glyburide/glibenclamide, tolbutamide, chlorpropamide | Close beta-cell KATP channels and stimulate insulin secretion independent of glucose | High | Gain |
| Meglitinides (glinides) | Repaglinide, nateglinide | Short, meal-linked insulin secretion | Moderate | Gain |
| Thiazolidinedione (TZD) | Pioglitazone; rosiglitazone in some formularies | PPAR-gamma activation increases insulin sensitivity | Low alone | Gain/fluid |
| Alpha-glucosidase inhibitor | Acarbose, miglitol | Delays intestinal carbohydrate digestion and absorption | Low | Neutral |
| DPP-4 inhibitor | Sitagliptin, linagliptin, saxagliptin, alogliptin, vildagliptin | Preserves endogenous GLP-1/GIP; glucose-dependent insulin and reduced glucagon | Low | Neutral |
| SGLT2 inhibitor | Empagliflozin, dapagliflozin, canagliflozin | Blocks proximal-tubule glucose reabsorption; glycosuria | Low alone | Loss |
| Oral GLP-1 receptor agonist | Semaglutide tablets | Glucose-dependent insulin, reduced glucagon, slower gastric emptying and appetite reduction | Low alone | Loss |
3. Metformin
Mechanism and pharmacology
Metformin activates cellular energy-sensing pathways (including AMP-activated protein kinase) and reduces hepatic gluconeogenesis. It improves peripheral insulin sensitivity and glucose uptake, and modestly reduces intestinal glucose availability. It does not directly force insulin release, so hypoglycaemia is uncommon when used alone. It is absorbed orally, has a short plasma half-life of approximately 3–6 hours, and is eliminated unchanged by the kidneys.
Indications
- First-line or foundational treatment for many adults with T2DM alongside diet, exercise and education.
- Combination therapy when glycaemia remains above target.
- Selected off-label uses such as polycystic ovary syndrome, only after evaluating pregnancy plans and local guidance.
Dose and titration
| Formulation | Starting dose | Titration/maximum | Administration |
|---|---|---|---|
| Immediate-release tablet | 500 mg once or twice daily with meals, or 850 mg once daily | Increase by 500 mg every 1–2 weeks as tolerated; usual effective dose 1,500–2,000 mg/day in divided doses; product maximum often 2,550 mg/day. | Take with meals to reduce nausea and diarrhoea. |
| Extended-release tablet | 500–1,000 mg once daily with the evening meal | Increase by 500 mg weekly; common maximum 2,000 mg/day (product-specific). | Swallow whole; do not crush extended-release tablets. |
Renal, contrast and acute-illness rules
- Obtain eGFR before starting and at least annually; assess more often in older adults or those at risk of deterioration.
- Metformin is contraindicated when eGFR is below 30 mL/min/1.73 m². Initiation is generally not recommended at eGFR 30–45; if already taking it, use a reduced dose and close review according to local guidance.
- Withhold during severe sepsis, shock, hypoxia, dehydration, acute kidney injury, major surgery and significant hepatic failure. Restart only when the acute risk has resolved and renal function is stable.
- Follow the local contrast-media policy; temporarily stop around iodinated contrast when renal injury risk is significant and recheck eGFR before restarting.
- Long-term therapy can reduce vitamin B12 absorption. Check B12 with anaemia, neuropathy, glossitis or risk factors and replace when deficient.
Adverse effects and contraindications
Common effects are nausea, abdominal discomfort, metallic taste, diarrhoea and reduced appetite. Slow titration or an extended-release preparation improves tolerance. Rare metformin-associated lactic acidosis is life-threatening and is more likely with renal failure, tissue hypoxia, sepsis, shock, severe heart failure, hepatic impairment, excess alcohol or interacting medicines.
- Contraindicated: eGFR below 30, acute or chronic metabolic acidosis including DKA, and hypersensitivity.
- Use caution: eGFR 30–45, hepatic impairment, unstable heart failure, heavy alcohol use, dehydration, severe infection and carbonic-anhydrase inhibitors such as topiramate.
Emergency: suspected metformin-associated lactic acidosis
Symptoms can be nonspecific—malaise, myalgia, abdominal pain, respiratory distress, somnolence, hypothermia or hypotension. Stop metformin, obtain venous/arterial blood gas, lactate, electrolytes, anion gap, glucose, renal and liver tests, and treat shock/hypoxia/sepsis. Severe acidosis, renal failure or high metformin exposure may require urgent haemodialysis because metformin is dialysable.
4. Sulfonylureas
Mechanism
Sulfonylureas bind the SUR1 subunit of beta-cell ATP-sensitive potassium channels, close the channel, depolarise the membrane, increase calcium influx and trigger insulin release. This action is largely glucose-independent; therefore hypoglycaemia may be prolonged, especially with long-acting agents, renal impairment, missed meals or alcohol.
Examples and practical doses
| Drug | Typical adult dose | Important cautions |
|---|---|---|
| Gliclazide immediate-release | 40–80 mg with breakfast; titrate every 1–2 weeks; usual 80–320 mg/day in divided doses. Modified-release commonly starts 30 mg once daily and may increase to 120 mg once daily. | Hypoglycaemia; use conservative dosing in older adults and kidney/liver disease. Follow the exact local formulation maximum. |
| Glimepiride | 1–2 mg once daily with breakfast/first meal; increase by 1–2 mg no more often than every 1–2 weeks; maximum 8 mg once daily. | Start 1 mg in elderly or renal impairment; prolonged hypoglycaemia is possible. |
| Glipizide | Usually 5 mg once daily before breakfast; titrate gradually. Immediate-release maximum often 40 mg/day; extended-release products have lower product-specific maxima. | Shorter acting than glyburide; still causes hypoglycaemia. |
| Glyburide/glibenclamide | Often 2.5–5 mg once daily with breakfast; titrate slowly; maximum depends on formulation. | Avoid or use extreme caution in older adults and renal impairment because active metabolites accumulate and hypoglycaemia can be prolonged. |
| Tolbutamide | 500 mg once or twice daily initially; usual 1–2 g/day in divided doses; maximum commonly 3 g/day. | Shorter half-life but less commonly used; hepatic/renal disease increases risk. |
| Chlorpropamide | 100–250 mg once daily; rarely used. | Very long acting; prolonged hypoglycaemia, hyponatraemia and disulfiram-like alcohol reaction. Generally avoid in older adults and renal disease. |
Adverse effects and contraindications
- Hypoglycaemia, weight gain, nausea, rash and rarely cholestatic jaundice, blood dyscrasias or hyponatraemia.
- Do not use for type 1 diabetes or DKA; use insulin instead.
- Avoid in severe hepatic failure, advanced renal impairment, recurrent severe hypoglycaemia and patients unable to eat reliably.
- Pregnancy and breastfeeding decisions require local specialist guidance; insulin is generally preferred when reliable control and fetal safety are paramount.
Interactions
NSAIDs, salicylates, warfarin, sulfonamides, macrolides, azole antifungals, fluoroquinolones, MAO inhibitors, alcohol and other glucose-lowering agents can increase hypoglycaemia. Corticosteroids, thiazide diuretics, sympathomimetics and some antipsychotics can raise glucose. Beta-blockers may mask adrenergic warning symptoms.
Hypoglycaemia treatment
If conscious and able to swallow, give 15–20 g fast-acting glucose, recheck in 15 minutes and repeat if needed, then provide a longer-acting carbohydrate. If unconscious, seizing or unable to swallow, place in the recovery position, give IV dextrose or IM glucagon according to local protocol, check for recurrent/prolonged hypoglycaemia and observe longer after a sulfonylurea overdose. Octreotide may be required by toxicology teams for recurrent sulfonylurea-induced hypoglycaemia.
5. Meglitinides (repaglinide and nateglinide)
Glinides bind a different site on the beta-cell potassium channel and produce rapid, short-duration insulin release. They mainly lower postprandial glucose and are taken with meals. The central rule is simple: skip the dose when the meal is skipped.
| Drug | Dose | Advantages | Risks/contraindications |
|---|---|---|---|
| Repaglinide | HbA1c below 8%: 0.5 mg before each meal. HbA1c 8% or higher: 1–2 mg before each meal. Titrate after at least one week; range 0.5–4 mg before meals; maximum 16 mg/day. Take within 30 minutes before meals; omit if no meal. | Flexible with irregular meal patterns; short action may reduce late hypoglycaemia compared with long-acting sulfonylureas. | Hypoglycaemia and weight gain; avoid with gemfibrozil, severe hepatic impairment, type 1 diabetes or DKA. |
| Nateglinide | 120 mg orally three times daily 1–30 minutes before meals; 60 mg three times daily if near glycaemic goal at initiation; omit when a meal is skipped. | Rapid onset and meal-linked action. | Hypoglycaemia, weight gain and caution in liver disease; not for type 1 diabetes/DKA. |
6. Thiazolidinediones (pioglitazone and rosiglitazone)
TZDs activate the nuclear receptor PPAR-gamma, which heterodimerises with RXR and changes transcription of genes involved in adipocyte differentiation, fatty-acid handling and insulin signalling. They improve insulin sensitivity in adipose tissue, skeletal muscle and liver but require endogenous insulin and have a slow onset over weeks.
Pioglitazone
- Dose: 15 or 30 mg orally once daily; titrate in 15-mg increments according to HbA1c; maximum 45 mg/day. In NYHA class I–II heart failure, start at 15 mg only and monitor closely.
- Benefits: durable insulin-sensitising effect; low hypoglycaemia risk alone; can improve fatty liver markers in selected patients.
- Adverse effects: weight gain, oedema, heart-failure exacerbation, fractures, anaemia, macular oedema and possible bladder-tumour concerns. Hypoglycaemia rises when combined with insulin or a secretagogue.
- Contraindication: initiation in symptomatic heart failure or NYHA class III–IV heart failure; do not start in active bladder cancer or unexplained visible haematuria until assessed.
- Monitoring: weight, ankle oedema, dyspnoea, liver tests before treatment and symptoms of fracture or visual change.
Rosiglitazone
Rosiglitazone is another PPAR-gamma agonist, but availability and cardiovascular restrictions vary by jurisdiction. It causes fluid retention, weight gain and heart-failure risk. Use only where approved and after reviewing current local safety guidance.
7. Alpha-glucosidase inhibitors
Acarbose and miglitol inhibit intestinal brush-border alpha-glucosidases, delaying breakdown of oligosaccharides and disaccharides to absorbable glucose. They mainly reduce the postprandial glucose rise and do not stimulate insulin.
| Drug | Dose | Adverse effects and warnings |
|---|---|---|
| Acarbose | Start 25 mg with the first bite of each main meal; in very sensitive patients start 25 mg once daily and increase frequency. After 4–8 weeks, increase to 50 mg three times daily; some require 100 mg three times daily. Maintenance 50–100 mg three times daily, product and body-weight dependent. | Flatulence, abdominal pain, diarrhoea and bloating. Avoid in inflammatory bowel disease, intestinal obstruction, malabsorption, cirrhosis or significant renal impairment according to product guidance. |
| Miglitol | Often 25 mg three times daily with the first bite; increase gradually to 50–100 mg three times daily as tolerated. | Gastrointestinal fermentation; renally cleared, so avoid or adjust in significant renal impairment. |
If hypoglycaemia occurs while an alpha-glucosidase inhibitor is combined with insulin or a secretagogue, treat with oral glucose (dextrose), not sucrose or ordinary table sugar, because sucrose digestion is delayed.
8. DPP-4 inhibitors
Mechanism
DPP-4 inhibitors prolong endogenous GLP-1 and GIP activity. They increase glucose-dependent insulin secretion and suppress inappropriate glucagon when glucose is elevated, producing modest HbA1c reduction with little hypoglycaemia or weight change.
| Drug | Usual dose | Renal adjustment | Key cautions |
|---|---|---|---|
| Sitagliptin | 100 mg once daily with or without food | eGFR 30–45: 50 mg once daily; eGFR below 30 or dialysis: 25 mg once daily | Pancreatitis, severe joint pain, bullous pemphigoid and hypersensitivity; reduce dose carefully. |
| Linagliptin | 5 mg once daily | No dosage adjustment generally required for renal impairment | Pancreatitis, hypersensitivity and severe arthralgia; avoid duplicate DPP-4 therapy. |
| Saxagliptin | 5 mg once daily | 2.5 mg once daily with renal impairment or strong CYP3A4/5 inhibitors | Heart-failure hospitalisation signal; consider alternatives in heart failure. |
| Alogliptin | 25 mg once daily | 12.5 mg daily for moderate and 6.25 mg daily for severe renal impairment | Heart failure, hepatic injury and pancreatitis warnings. |
| Vildagliptin | Usually 50 mg once or twice daily depending on combination and local label | Reduce in renal impairment according to product label | Liver-function monitoring is important; availability varies. |
DPP-4 inhibitors should not be combined with GLP-1 receptor agonists because they act on the same incretin pathway without useful additive efficacy. Hypoglycaemia risk increases when combined with insulin or a sulfonylurea, so reduce the secretagogue if appropriate.
9. SGLT2 inhibitors
Mechanism and clinical benefits
SGLT2 inhibitors reduce glucose and sodium reabsorption in the proximal renal tubule, increasing urinary glucose excretion and natriuresis. The glucose-lowering effect decreases as eGFR falls, but heart-failure and chronic-kidney-disease benefits may persist at eGFR thresholds specified by the current product and guideline.
| Drug | Typical adult dose for T2DM | Important use limits |
|---|---|---|
| Empagliflozin | 10 mg once daily in the morning; may increase to 25 mg once daily for additional glycaemic control if renal function and label permit. | Check eGFR and volume status; not a treatment for type 1 diabetes or DKA. |
| Dapagliflozin | 5 mg once daily for glycaemic control; increase to 10 mg once daily if needed and permitted. | Renal thresholds differ by indication; do not assume a diabetes dose is appropriate for heart failure/CKD. |
| Canagliflozin | 100 mg once daily before the first meal; may increase to 300 mg once daily in selected patients with adequate renal function. | Monitor renal function, volume status, foot health and fracture/amputation risk according to current label. |
Adverse effects, contraindications and sick-day rules
- Genital candidiasis, urinary infection, polyuria, dehydration, orthostatic hypotension and acute kidney injury can occur.
- Euglycaemic DKA may present with nausea, abdominal pain, tachypnoea and ketones despite only modest glucose elevation.
- Hold during prolonged fasting, vomiting, severe infection, major surgery, dehydration or suspected ketoacidosis. Many protocols stop 3 days before major surgery; longer may be required for some agents.
- Avoid initiation in type 1 diabetes, active DKA, severe volume depletion and below the product-specific eGFR threshold. Review diuretics and antihypertensives.
- Educate about genital hygiene, adequate fluid intake and early reporting of genital pain, fever, perineal swelling or severe malaise (rare Fournier gangrene).
Emergency: SGLT2-associated euglycaemic DKA
Stop the SGLT2 inhibitor, check capillary/serum beta-hydroxybutyrate, venous blood gas, electrolytes, anion gap, renal function and glucose. Treat as DKA with IV fluids, insulin and potassium replacement according to the emergency protocol; dextrose may be needed early because glucose is not very high. Do not discharge because the glucose appears acceptable.
10. Oral semaglutide (GLP-1 receptor agonist)
Oral semaglutide is absorbed through a specialised formulation and activates the GLP-1 receptor. It increases glucose-dependent insulin, reduces glucagon, slows gastric emptying and decreases appetite. It is used in T2DM, and some products have cardiovascular-risk indications; it is not a substitute for insulin in type 1 diabetes or DKA.
- Initiation: 3 mg once daily for 30 days; this is a starter dose and is not intended to provide full glycaemic control.
- Escalation: 7 mg once daily from day 31; if additional control is needed after at least 30 days, increase to 14 mg once daily.
- Administration: take on an empty stomach immediately on waking with no more than 120 mL (4 ounces) of plain water; swallow whole. Wait at least 30 minutes before food, drinks or other oral medicines.
- Common adverse effects: nausea, vomiting, diarrhoea, constipation and reduced appetite, especially during titration.
- Serious warnings: pancreatitis, gallbladder disease, dehydration-related kidney injury, diabetic retinopathy complications during rapid glucose improvement and severe gastrointestinal disease. Avoid in patients with personal/family history of medullary thyroid carcinoma or MEN2 where the product is contraindicated.
- Hypoglycaemia: uncommon alone but rises with insulin or sulfonylureas; reduce the secretagogue when clinically appropriate.
11. Combination therapy and rational selection
| Patient profile | Reasonable pharmacologic direction | Usually avoid or reconsider |
|---|---|---|
| New T2DM without cardiorenal disease | Metformin if safe; add an agent based on HbA1c, weight, cost and preferences. | Secretagogue monotherapy if severe hypoglycaemia risk. |
| Established ASCVD or obesity | GLP-1 receptor agonist with proven benefit; SGLT2 inhibitor if appropriate. | Weight-gaining drugs when weight reduction is a major goal. |
| Heart failure or CKD | SGLT2 inhibitor when eGFR and volume status permit; optimise standard cardiorenal care. | Pioglitazone in symptomatic heart failure; saxagliptin where heart-failure risk is concerning. |
| Irregular meals/limited food security | Metformin, DPP-4 inhibitor or another low-hypoglycaemia option; provide social support. | Long-acting sulfonylurea and unsupervised glinide escalation. |
| Severe hyperglycaemia, catabolism, ketosis or weight loss | Urgent assessment and often insulin rather than escalating oral agents. | Delaying insulin in DKA, HHS or symptomatic insulin deficiency. |
| Advanced renal impairment | Use renal-adjusted DPP-4 inhibitor or specialist plan; review insulin because clearance may fall. | Metformin below eGFR 30; glyburide and unadjusted renally cleared agents. |
12. Monitoring
- Glycaemia: HbA1c at baseline and usually every 3 months until stable, then every 3–6 months; self-monitoring when using secretagogues, insulin, pregnancy, illness or symptoms.
- Kidney: eGFR and urine albumin-to-creatinine ratio at least annually, more frequently in CKD or with metformin/SGLT2 therapy.
- Liver: baseline liver tests for metformin, TZD and agents with hepatic warnings; repeat when symptoms or risk factors occur.
- Weight and volume: check oedema and dyspnoea with pioglitazone; weight, dehydration and blood pressure with SGLT2 therapy; appetite and nutritional state with GLP-1 therapy.
- Hypoglycaemia review: ask about missed meals, alcohol, exercise, driving, nocturnal symptoms and access to glucose or glucagon.
- Foot/skin and infection: inspect feet and ask about genital symptoms when using an SGLT2 inhibitor.
- Vitamin B12: periodically assess in long-term metformin users with anaemia, neuropathy or risk factors.
13. Drug interactions
| Interaction | Clinical consequence | Response |
|---|---|---|
| Metformin + iodinated contrast/acute kidney injury | Accumulation and lactic acidosis risk | Follow local temporary-withholding protocol and recheck eGFR. |
| Metformin + alcohol, topiramate or severe hypoxia | Increased lactic acidosis risk | Avoid excess alcohol; review carbonic-anhydrase inhibitors and acute illness. |
| Sulfonylurea/glinide + NSAIDs, sulfonamides, macrolides, azoles, warfarin or alcohol | More severe/prolonged hypoglycaemia | Check glucose more frequently and adjust/withhold the secretagogue. |
| Repaglinide + gemfibrozil | Marked increase in repaglinide exposure and hypoglycaemia | Contraindicated; use another lipid-lowering strategy. |
| Pioglitazone + insulin/NSAIDs | Oedema and heart-failure risk | Monitor weight, dyspnoea and oedema; avoid in symptomatic HF. |
| DPP-4/GLP-1 agent + insulin or sulfonylurea | Additive hypoglycaemia | Consider reducing the secretagogue dose. |
| SGLT2 inhibitor + loop/thiazide diuretic | Volume depletion, hypotension or AKI | Assess blood pressure, hydration and renal function; give sick-day advice. |
| SGLT2 inhibitor + ketogenic diet/fasting/acute infection | Euglycaemic DKA | Withhold during risk period and check ketones if unwell. |
14. Emergencies for emergency-medicine students
Severe hypoglycaemia
ABC assessment, bedside glucose, IV dextrose if access is available or IM glucagon if not; protect the airway, recheck frequently and observe longer after sulfonylurea overdose. Identify the drug and meal history.
Metformin lactic acidosis
Stop metformin, treat shock/sepsis/hypoxia, measure lactate and acid-base status, correct electrolytes and contact renal/toxicology teams; haemodialysis may be lifesaving.
SGLT2 euglycaemic DKA
Check ketones and anion gap even when glucose is below 250 mg/dL (13.9 mmol/L). Stop SGLT2 therapy and treat with fluids, insulin, potassium and dextrose as indicated.
Pioglitazone heart-failure flare
Stop/review pioglitazone in new oedema, orthopnoea or rapid weight gain; assess oxygenation, ECG, renal function and pulmonary oedema, then treat acute heart failure.
15. Clinical cases
Case 1 — metformin and acute sepsis
A patient taking metformin presents hypotensive with pneumonia, lactate 6 mmol/L and rising creatinine. Withhold metformin immediately, resuscitate, treat sepsis and hypoxia, repeat lactate/acid-base/renal tests and involve critical-care/renal teams. Do not attribute the lactate solely to metformin without correcting the underlying shock.
Case 2 — recurrent hypoglycaemia after glibenclamide
A confused patient repeatedly becomes hypoglycaemic after IV dextrose. Ask about a sulfonylurea, continue dextrose with frequent glucose checks, observe for a prolonged period and contact toxicology; octreotide may be needed for recurrent secretion-driven hypoglycaemia.
Case 3 — normal glucose but ketotic acidosis
A patient on dapagliflozin has vomiting, tachypnoea, anion-gap acidosis and beta-hydroxybutyrate 5 mmol/L with glucose 8.5 mmol/L. Diagnose possible euglycaemic DKA, stop the drug and begin DKA treatment rather than discharging because the glucose is not high.
Case 4 — pioglitazone and oedema
A patient gains 5 kg in three weeks and develops orthopnoea after pioglitazone is added to insulin. Suspect fluid retention/heart-failure exacerbation. Stop or withhold pioglitazone, assess for pulmonary oedema and revise the diabetes regimen after stabilisation.
Case 5 — acarbose hypoglycaemia
A patient taking acarbose with a sulfonylurea becomes sweaty and confused. Treat with glucose/dextrose rather than sucrose, because alpha-glucosidase inhibition delays sucrose breakdown, and review the secretagogue dose and meal pattern.
16. High-yield revision points
- Metformin reduces hepatic gluconeogenesis and is usually weight-neutral, but renal failure/hypoxia can precipitate lactic acidosis.
- Sulfonylureas stimulate insulin regardless of glucose; prolonged hypoglycaemia is the defining danger.
- Glinides are short acting and meal-linked: no meal, no dose.
- Pioglitazone improves insulin sensitivity but causes weight gain, oedema and heart-failure exacerbation.
- Acarbose acts in the gut; treat combined-therapy hypoglycaemia with glucose, not sucrose.
- DPP-4 inhibitors are weight-neutral and low risk for hypoglycaemia; adjust sitagliptin for renal impairment, while linagliptin generally needs no renal adjustment.
- SGLT2 inhibitors cause glycosuria, genital mycosis and volume depletion; remember euglycaemic DKA.
- Oral semaglutide must be taken fasting with a small amount of water and separated from food/other tablets by at least 30 minutes.
- DKA, HHS, severe symptomatic hyperglycaemia and type 1 diabetes require insulin-based emergency management, not oral escalation.
17. Sources and further reading
- Supplied SlideShare: Oral hypoglycemics.
- DailyMed: metformin hydrochloride prescribing information.
- DailyMed: glimepiride.
- DailyMed: repaglinide.
- DailyMed: nateglinide.
- DailyMed: pioglitazone.
- DailyMed: sitagliptin.
- DailyMed: linagliptin.
- DailyMed: acarbose.
- DailyMed: dapagliflozin.
- DailyMed: oral semaglutide.
This page is for supervised medical education. Doses, eGFR thresholds, approved indications and pregnancy recommendations vary by product and country. Verify the current local formulary and product information before prescribing.
