Pharmacotherapy of 'treatment resistant' type 2 diabetes.

INTRODUCTION: Despite type 2 diabetes (T2D) management offers a variety of pharmacological interventions targeting different defects, numerous patients remain with persistent hyperglycaemia responsible for severe complications. Unlike resistant hypertension, treatment resistant T2D is not a classical concept although it is a rather common observation in clinical practice. Areas covered: This article proposes a definition for 'treatment resistant diabetes', analyses the causes of poor glucose control despite standard therapy, briefly considers the alternative approaches to glucose-lowering pharmacotherapy and finally describes how to overcome poor glycaemic control, using innovative oral or injectable combination therapies. Expert opinion: Before considering intensifying the pharmacotherapy of a patient with poorly controlled T2D, it is important to verify treatment adherence, target obesity and consider various non pharmacological improvement quality interventions. If treatment resistant diabetes is defined as not achieving glycated haemoglobin target despite oral triple therapy with a third glucose-lowering agent added to metformin-sulfonylurea dual treatment, the combination of a dipeptidyl peptidase-4 (DPP-4) inhibitor and a sodium glucose cotransporter type 2 (SGLT2) inhibitor may offer new opportunities before considering injectable therapies. Insulin basal therapy (+/- metformin) may be optimized by the addition of a SGLT2 inhibitor or a glucagon-like peptide-1 (GLP-1) receptor agonist.