Exercise 5 — Answer

Clinical Summary

Drug of Choice: Metformin (Biguanide)

• First-line agent for all newly diagnosed T2DM patients (ADA/WHO guidelines) in the absence of contraindications.
• Ideal for obese patients (BMI 31.8) — it is weight-neutral to weight-reducing, unlike sulfonylureas or insulin which cause weight gain.
• HbA1c of 10.9% is significantly elevated; metformin alone may not bring it to target (<7%), so dual therapy is often initiated when HbA1c >9–10%, but metformin remains the backbone.
• No cardiovascular, renal, or hepatic contraindications mentioned.
• Reduces HbA1c by ~1–2%.
• Cheap, well-tolerated, proven cardiovascular safety (UKPDS data).

Note on dual therapy: Since HbA1c is 10.9% (>9%), current ADA guidelines recommend dual therapy at initiation. Given obesity and no cardiovascular disease, Metformin + an GLP-1 receptor agonist (e.g., liraglutide) or Metformin + SGLT-2 inhibitor (e.g., empagliflozin) would be optimal — both offer additional weight reduction benefit. However, if the question expects a single primary drug, Metformin is the answer.

Prescription

Rx

Patient: [Name], 40F
Date: [Date]

1. Tab. Metformin 500 mg
   — Take 1 tablet TWICE daily with meals (breakfast & dinner)
   — Titrate to 1000 mg twice daily over 4–8 weeks as tolerated
   — Route: Oral

   (Target dose: 1500–2000 mg/day)

2. Continue dietary modifications and exercise as prescribed.

3. Monitor:
   — FBS & PPBS: monthly for 3 months
   — HbA1c: after 3 months
   — Renal function (eGFR, serum creatinine): at baseline and every 6 months
   — LFTs: baseline

4. Counsel patient:
   — Take with food to minimize GI side effects (nausea, diarrhea)
   — Avoid alcohol
   — Do not take if contrast dye/surgery planned (hold 48 hours)
   — Signs of hypoglycemia (unlikely with metformin monotherapy)

Follow-up in 4 weeks.

Dr. [Name]
Reg. No.: [XXXX]

Key Pharmacology Points

Exercise 5 (ii) — Full Answer

Clinical Summary

YES — All three drugs must be changed

Why Each Current Drug is Harmful:

1. ❌ Metformin 2 g/day — STOP

• Metformin is renally cleared and accumulates in renal failure.
• Accumulation → Lactic acidosis (life-threatening).
• Contraindicated when serum creatinine >1.5 mg/dL (male) / >1.4 mg/dL (female), or eGFR <30 mL/min.
• This patient has creatinine 3.8 mg/dL — severely contraindicated. Must be stopped immediately.

2. ❌ Pioglitazone 15 mg/day — STOP

• Thiazolidinediones (TZDs) act on PPAR-γ → increase sodium and water reabsorption in renal tubules → peripheral oedema and fluid retention.
• This patient already has pedal oedema and exertional dyspnoea — classic signs of fluid overload/heart failure.
• Pioglitazone is contraindicated in heart failure (NYHA Class I–IV) and in patients with oedema.
• Pioglitazone is also best avoided in severe renal impairment.
• Must be stopped.

3. ⚠️ Glimepiride 2 mg/day — STOP / Use with extreme caution

• Glimepiride is a sulfonylurea — its active metabolites are renally excreted.
• In CKD, metabolites accumulate → severe, prolonged hypoglycaemia.
• The kidney also has reduced gluconeogenesis → further hypoglycaemia risk.
• Generally avoided or used at very low doses in significant CKD. With creatinine 3.8, it should be stopped.

Drug of Choice (p drug) for This Patient

• Severe CKD (creatinine 3.8)
• Oedema + exertional dyspnoea (probable heart failure)
• HbA1c 8.9%

✅ Insulin — Drug of Choice

• Insulin is the safest antidiabetic agent in severe renal impairment — it is metabolised in the kidney and liver, but dose can be carefully titrated.
• No risk of lactic acidosis (unlike metformin), no fluid retention (unlike TZDs), no active metabolite accumulation causing hypoglycaemia (unlike sulfonylureas).
• Provides reliable glycaemic control regardless of renal function.
• Short-acting or intermediate-acting insulin (e.g., Human Mixtard or Basal-Bolus) can be used with careful dose reduction (CKD reduces insulin clearance, so lower doses needed).

Note on the handwritten hint (Salbutamol / Terbutaline): These are β₂-agonists used for bronchospasm. They are NOT appropriate here — the dyspnoea is cardiac/fluid-related (heart failure), not bronchospasm. Salbutamol/Terbutaline would be inappropriate and potentially harmful (can worsen tachycardia in a cardiac patient). The handwritten suggestion appears to be a student error — do not follow it.

Revised Prescription

Rx

Patient: 55-year-old Male, T2DM with CKD (Cr 3.8 mg/dL) + Oedema

STOP: Metformin, Pioglitazone, Glimepiride (all contraindicated)

START:

1. Inj. Human Insulin (Intermediate-acting: NPH / Mixtard 30/70)
   — 0.3–0.5 units/kg/day as starting dose
   — Divided: 2/3 in morning, 1/3 at bedtime (BD regimen)
   — Subcutaneous injection
   — Titrate based on fasting & post-prandial blood glucose monitoring
   — (Use lower doses than usual — CKD reduces insulin clearance)

2. Monitor blood glucose: fasting and 2-hour post-meal daily

3. Manage heart failure/oedema:
   — Refer to cardiologist/nephrologist
   — Consider furosemide for oedema (if not already prescribed)

4. Nephrology referral for CKD Stage 4 management

5. Monitor: eGFR, serum creatinine, K⁺ (risk of hyperkalaemia in CKD)

Follow-up in 2 weeks.

Dr. [Name] | Reg. No.: XXXX

Summary Table