Oral/Subcut hypoglycaemic agents

Drugs A - Z

• Alogliptin
• Canagliflozin
• Dapagliflozin
• Empagliflozin
• Exenatide
• Gliclazide
• Glimepiride
• Linagliptin
• Liraglutide
• Metformin
• Pioglitazone
• Saxagliptin
• Sitagliptin
• Vildagliptin

Metformin

• Metformin may be associated with lactic acidosis in critically ill patients with shock, hepatic impairment or acute and chronic renal failure.

• Metformin should be suspended in patients with:

  • No enteral route / surgical contraindication to enteral medication
  • Shock requiring > 10ml/hr noradrenaline (4mg in 50ml) or equivalent
  • Acute or chronic liver failure
  • Acute kidney injury (AKI) Stage 2 or 3 (increase serum creatinine >200%, urine output < 0.5ml/kg/hr for >12hrs or on renal replacement therapy).
  • Lactate > 2.0 mmol/L

• Restarting metformin may reduce insulin requirements in patients taking both agents: involve DSN colleagues when metformin is due to restart so insulin dose adjustments can be considered.

• Metformin may be associated with improved survival in patients presenting to critical care who have Type 2 diabetes and are already taking metformin or have sepsis. It may reduce the need for intravenous insulin and therefore minimise glycaemic variability, so continuation is to be considered in the absence of risk factors above.

• Metformin dose may need adjusting according to eGFR in chronic renal failure, with a stable AKI or on CVVH: seek pharmacy advice.

• In patients admitted with a high HbA1c (>48 mmol/L) who are requiring intravenous insulin to control hyperglycaemia, consider starting metformin once full feed is established if none of the above contraindications are present. The recommended starting dose is lower at 500mg bd to reduce the risk of GI side effects with subsequent titration by the Diabetes Specialist Team.

Metformin protocol

GLP-1 analogues

• Glucagon-like peptide 1 (GLP-1) analogues (Exenatide and Liraglutide) are subcutaneously administered medications and absorption may be unpredictable in critically ill patients. They should be discontinued in patients admitted to critical care.

• The GLP-1 analogues act by increasing incretin levels which reduce gastric emptying. A common side effect is nausea and vomiting. If, after restarting these agents, there are concerns regarding high gastric aspirates, paralytic ileus or vomiting then these agents should be suspended.

DPP-4 inhibitors

• Dipeptidyl peptidase-4 (DPP-4) inhibitors (Sitagliptin, Alogliptin, Vildagliptin, Saxagliptin and Linagliptin) are oral agents that stimulate incretin release and suppress glucagon. They have a similar mechanism of action to the GLP-1 analogues and should be stopped on admission but could be reintroduced once the individual has started to eat normally.

• DPP-4 inhibitors should be discontinued in high gastric aspirates, nausea or vomiting or in individuals with pancreatitis, ketoacidosis, or moderate to severe heart failure

SGLT-2 inhibitors

• Sodium-glucose co-transporter 2 (SGLT-2) inhibitors (Canagliflozin, Dapagliflozin or Empagliflozin) should be held on admission to and not restarted until eating and drinking normally. They should be omitted for 48 hours in patients undergoing elective surgery.

• SGLT-2 inhibitors are also used in acute and chronic heart failure (HF). It may be advantageous to restart these drugs earlier in HF patients: liaise with a cardiologist.

• SGLT-2 inhibitors reduce the renal reabsorption of glucose and are associated with an osmotic diuresis which may cause profound hypovolaemia. They are associated with a euglycaemic ketoacidosis that may exist for several days after discontinuation of treatment. This a particular risk to critically ill patients. Unexplained acidosis in a patient admitted who has been taking a SGLT-2 inhibitor should prompt investigation for ketoacidosis even in the context of normal glucose levels. Treatment of this condition is supportive with fluid resuscitation and continuation of an insulin and glucose infusion, ketones should be monitored for 48-72 hours after treatment has been suspended.

Sulphonylureas

• The sulphonylureas (Gliclazide and Glimepiride) cause insulin release by direct binding to receptors on beta cells. They are associated with hypoglycaemia. Critically ill patients with unpredictable absorption and renal clearance may be at higher risk.

• Gliclazide and glimepiride should be suspended on admission to critical care and blood glucose should be monitored closely (every 4-6 hours) for up to 48 hours if the patient has any evidence of renal impairment.

• If blood glucose is found to be below 6 mmol/L in a patient who has been taking sulphonylureas prior to admission to critical care, consider starting a background glucose infusion until full feed is established to minimise the risk of a hypoglycaemia.

• Sulphonylureas should not be restarted until the patient is well enough to discharge to ward level care, is eating or has enteral route established and has been reviewed by the Diabetes Specialist nurse.

Thiazolidinediones

• Thiazolidinediones (Pioglitazone) act via nuclear receptors to increase free fatty acid uptake into adipocytes which results in an increase in glucose metabolism.

• Their action at nuclear receptors results in a markedly prolonged duration of action even after the drug is discontinued.

• They are associated with an increased risk of hypoglycaemia and in chronic use associated with peripheral oedema, fluid retention and exacerbation of congestive cardiac failure.

• Pioglitazone should be suspended on admission to critical care and blood glucose should be monitored closely (every 4-6 hours) for up to 48 hours if the patient has any evidence of renal impairment.

• Thiazolidinediones should not be restarted until the patient is well enough to discharge to ward level care, is eating or has enteral route established and has been reviewed by the Diabetes Specialist nurse.