MRCP UK

Renal dosing for DPP-4 inhibitors

Linagliptin: No dose adjustment required at any stage of CKD (exam favorite).
Sitagliptin: Dose reduction required as eGFR falls.
Saxagliptin: Dose reduction required.
Alogliptin: Dose reduction required.

DPP-4 inhibitors were preferred in CKD because many other glucose-lowering agents were limited by renal function. However, current guidelines increasingly prioritize SGLT2 inhibitors and GLP-1 receptor agonists

CKD + need for a glucose-lowering drug with low hypoglycemia risk → think DPP-4 inhibitor, especially Linagliptin.

CKD + desire to slow kidney disease progression and reduce cardiovascular events → think SGLT2 inhibitor first (if eGFR permits).

Metformin

Crohn’s Disease: Options After Anti-TNF Failure

If a patient fails an anti-TNF agent (e.g., Infliximab or Adalimumab), management depends on whether the failure is primary non-response or secondary loss of response.

Assess the reason for failure

Check drug levels and anti-drug antibodies (therapeutic drug monitoring).
Low drug level ± antibodies → optimize dose or switch within anti-TNF class.
Adequate drug level but active disease → switch to a different mechanism of action.

Biologic / Advanced Therapy Options

1. Ustekinumab (anti-IL-12/23)

Effective after anti-TNF failure.
Often preferred when systemic efficacy is desired.

2. Vedolizumab (anti-α4β7 integrin)

Gut-selective.
Useful when infection risk is a concern.

3. Upadacitinib (JAK1 inhibitor)

Oral therapy.
Effective in moderate-to-severe Crohn’s disease after biologic failure.

4. Risankizumab (anti-IL-23)

Strong efficacy data in patients with prior anti-TNF exposure.
Increasingly favored in many treatment algorithms.

Hypokalemia + metabolic alkalosis + normal/low BP
→ Think:

Vomiting
Diuretic use
Bartter Syndrome
Gitelman Syndrome

Exam pearl: Measure urinary chloride.

Low urine chloride (20 mmol/L) → diuretics, Bartter, Gitelman

Hypertension + hypokalemia
→ Think mineralocorticoid excess, especially:

Primary Hyperaldosteronism
Secondary hyperaldosteronism
Cushing Syndrome
Apparent mineralocorticoid excess (e.g., liquorice ingestion)

Hypokalemia + episodic weakness + hyperthyroidism
→ Think Thyrotoxic Periodic Paralysis.

Conditions where TSH may be elevated without established primary hypothyroidism

Consider:

Obesity
Recovery from non-thyroidal illness
Primary adrenal insufficiency
Certain drugs (especially lithium and amiodarone)
Laboratory interference
Early autoimmune thyroid disease

If TSH is elevated and free T4 is elevated, think of:

1. TSH-secreting pituitary adenoma
2. Thyroid hormone resistance
3. Assay interference