Triple therapy in diabetes, what’s the third line?

When the NICE updated the clinical guideline for management of hyperglycaemia in 2009 (CG87) it reiterated the place of metformin and sulphonylureas as first- and second-line treatments respectively. However, what is recommended when dual therapy does not achieve HbA1c targets?

By default, NICE CG87 suggests that insulin is first choice for all patients by stating that oral agents should only be used when ‘insulin is unacceptable or inappropriate’. The insulin NICE recommends is human NPH with progression to long-acting analogues only in those experiencing hypoglycaemia or needing third party administration.

Where insulin is not used, oral agents may be considered for third line. Pioglitazone, having just survived an EMA review, is preferable in patients with ‘marked insulin insensitivity’ and in whom there is no increased risk of heart failure or bony fracture. Gliptins (although only sitagliptin has a triple therapy licence) are preferred where weight gain would ‘cause or exacerbate problems’. Both therapy classes should only be continued if they reduce the HbA1c by 0.5% in six months.

Another third line in patients with a BMI >35Kg/m2, GLP-1 injectables (exenatide and liraglutide) can be considered but need to achieve both an HbA1c reduction of 1% and weight loss of 3% in 6 months. Patients with lower BMIs may be eligible for GLP-1 if they would benefit from weight loss or lose their job if prescribed insulin.

Professor Steve Bain