Introduction
This section provides guidance and information on non-insulin therapies i.e. oral agents and other injectable options used to achieve glycaemic control in patients with type 2 diabetes. It is important to understand:
how these drugs are used to treat type 2 diabetes
the adverse effects of these drugs
when these drugs may need to be stopped or changed in acute illness
General principles – glucose lowering therapies
Metformin is often used as first line treatment in type 2 diabetes unless not tolerated or contraindicated. Second line treatment is added when the first line therapy fails to achieve the target glycaemic control. The choice of second line therapy, includes sulfonylureas, DPP-4 inhibitors, GLP-1 analogues, SGLT-2 inhibitors and insulin (for insulin, see chapter on Insulin therapy). Choice of agent depends on the needs and preferences of the person. There are various factors such as effect on weight, cardiovascular benefits, potential to lower HbA1c, adverse effect profile that are taken into consideration when prescribing second line therapy. Below is a diagram giving an overall approach to glucose lowering therapy in type 2 diabetes .
The available treatments and their characteristics (eg, hypo risk, use in CKD, etc) are summarised in the table below. Renal function and the adverse effect profile of treatments should be reviewed when patients with diabetes are admitted to hospital.
General advice for patients with type 2 diabetes who are unwell
During periods of illness, people with type 2 diabetes should be advised:
| • To keep well hydrated (3 l fluid/day). Maintain a normal meal pattern where possible. |
| • Capillary blood glucose levels should be monitored at least every 4 hrs and at bedtime |
| • For acutely unwell patients / significant renal impairment (creatinine >130 µmol/L and eGFR <45 mL/min) / decompensated cardiac failure / liver failure / lactic acidosis then continue insulin (review dose) but withhold SGLT2 inhibitors, metformin and GLP-1 analogues until recovered. Note: Possible risk of euglycaemic DKA with SGLT2 inhibitors |
| • Patients on sulfonylureas are at higher risk of hypoglycemia with impaired renal function. Monitor blood glucose levels closely, reduce dose if appropriate and offer snacks at bedtime to reduce the risk of hypoglycaemia. |
| • If acutely unwell / severe sepsis / vomiting / drowsy / unable to keep fluids down / suffering with persistent diarrhoea patient needs medical review immediately. If the blood glucose levels are raised, check urine/blood ketone and pH and bicarbonate. Refer to guidance on management of hyperglycaemiea (link this sentence to the hyperglycaemia decision support tool). If DKA and HHS present initiate immediate treatment (see chapter on Diabetes Emergencies). If DKA and HHS ruled out then patient will require variable rate intravenous insulin infusion (VRIII) (see chapter on Intravenous insulin). If in any doubt seek an urgent senior review and refer to the diabetes team |
Less commonly used therapies such as α-glucosidase inhibitors (e.g., acarbose) and meglitinides (e.g., repaglinide, nateglinide) are not included in the table. It is worth noting that repaglinide is a major substrate of CYP3A4 and should not be administered concomitantly with gemfibrozil, clarithromycin or certain anti-fungals like itraconazole or ketoconazole due to increased risk of hypoglycaemia.
Refs: SGLT2 Inhibitors in Type 2 Diabetes Management: Key Evidence and Implications for Clinical Practice
Davies et al, Diabetes Care Sep 2018, dci180033; DOI: 10.2337/dci18-0033