Emerging treatment options for type 2 diabetes

Abstract

Type 2 diabetes mellitus (T2DM) is rapidly increasing in prevalence and is a major public health problem. It is a progressive disease which commonly requires multiple pharmacotherapy. Current options for treatment may have undesirable side effects (particularly weight gain and hypoglycaemia) and contraindications, and little effect on disease progression. Incretin based therapy is one of several newer therapies to improve glycaemia and is available in two different forms, dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists. Use of these agents results in a 'glucose-dependant' increase in insulin secretion and glucagon suppression resulting in improved glycaemia with low incidence of hypoglycaemia. DPP-4 inhibitors are oral drugs which are weight neutral, while GLP-1 agonists are injected subcutaneously and help promote weight loss while improving glycaemia. GLP-1 agonists have also been shown to increase beta cell mass in rat models. Bariatric surgery is another option for the obese patient with T2DM, with blood glucose normalizing in over half of the patients following surgery. Other therapies in development for the treatment of T2DM include sodium-glucose transporter 2 (SGLT-2) inhibitors, glucagon receptor antagonists, glucokinase activators and sirtuins. In this article, we will review the various existing and emerging treatment options for T2DM.

Figure 1

Changing physiology and clinical complications in the natural history of type 2 diabetes. Data extrapolated. Adapted from: Holman RR. Diabetes Res Clin Pract 1998; 40 (Suppl.): S21–5 [162]; Ramlo-Halsted BA, Edelman SV. Prim Care 1999; 26: 771–89 [163]; Nathan DM. N Engl J Med 2002; 347: 1342–9 [164]

Figure 2

Current therapeutic implications of progressively declining beta-cell function and change in HbA1c in type 2 diabetes. Heine RJ et al. BMJ 2006; 333: 1200–4 [165]