- Act in a similar manner to sulphonylureas, closing β-cell KATP channels
- The resulting depolarisation opens voltage-gated Ca2+ channels and Ca2+ influx triggers insulin release
- Their shorter duration of action may reduce late hypoglycaemia compared with sulphonylureas
Meglitinides
Meglitinides
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- Meglitinides (e.g. repaglinide, nateglinide) are short-acting insulin secretagogues
- Repaglinide is the only meglitinide currently available in the UK, and is no longer recommended in NICE guidance so is rarely used
- Their rapid onset and short duration suit patients with erratic meal patterns, as doses are taken with meals
Absorption
- Rapid oral absorption; bioavailability of repaglinide approximately 50%
Distribution
- Highly protein bound (~98%)
Metabolism
- Hepatic metabolism by CYP450 enzymes (CYP2C8 and CYP3A4), so subject to drug interactions
- Clarithromycin, itraconazole and clopidogrel may prolong the hypoglycaemic effect of repaglinide
Excretion
- Elimination half-life ~1hr
- Predominantly non-renal excretion, which is beneficial in renal impairment
Nutritional and metabolic
- Hypoglycaemia, although the risk appears to be lower than with sulphonylureas
- Weight gain
Gastrointestinal
- GI disturbance
Perioperative management
- UK recommendations depend on the timing of surgery and the fasting period:
- Morning surgery: omit the morning dose
- Afternoon surgery: take the morning dose if eating breakfast
- Of note the American, Australian and Canadian guidelines simply recommend withholding on the day of surgery
- Patients on a liver reduction diet or bowel preparation may need a longer cessation period
- Target capillary blood glucose 6-10mmol/L
- Restart once eating and drinking normally and any VRII has been stopped
- Review after bariatric surgery owing to rapid falls in glucose
- Stop in critical illness