Deciding oral drugs after metformin in type 2 diabetes: An evidence-based approach

Abstract

The most commonly used oral drug in treating type 2 diabetes (T2DM) after metformin are sufonylureas (SUs) based on the confidence gained over the several decades and because of its cheaper cost. Unfortunately, SUs are associated with secondary failure and sometimes associated with therapy related severe hypoglycaemia limiting its compliance and wider utility in current clinical practice. Although large randomised trials could not associate SUs with any obvious increase in cardiovascular (CV) mortality, some recent larger databases showing divergent results suggesting increasingly CV signals and this might put SUs in difficulty given the availability of other safer alternatives. In recent years, incretin-based therapies like dipeptidyl peptidase-4 inhibitors (DPP-4I) and glucagon-like peptide-1 (GLP-1) agonist (GLP-1A) are gaining popularity primarily because of their advantage of weight reduction/neutrality and minimal hypoglycemia along with the perception of possible pleiotropic CV benefit mainly derived from pooled CV data of their trials. Sodium glucose transporter 2 inhibitors (SGLT-2I) are another new promising molecule currently looking for its space in the management of T2DM. Insulin could be utilized at any place when required and in this regard outcomes reduction with an initial glargine intervention (ORIGIN) study also suggested that basal insulin glargine could be safely used even in early stage. This review will discuss what could be possibly be the best option as a second line oral agent, once metformin monotherapy becomes ineffective.

Keywords

• Cardiovascular mortality
• dipeptidyl peptidase-4 inhibitors
• incretin based therapies
• Sodium glucose transporter 2-2 inhibitors
• sulfonylureas
• type 2 diabetes