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This review considers the therapeutic choices currently faced by people with type 2 diabetes and those caring for them when glucose levels initially controlled with lifestyle management and metformin start to rise. While sulphonylureas are familiar agents and cheaper than other alternatives, they cause hypoglycaemia and modest weight gain, and robust outcome data are still lacking. Dipeptidyl peptidase 4 inhibitors ('gliptins') have an attractive pharmacological and adverse effect profile, but their effects on the cardiovascular system are also uncertain. Thiazolidinediones ('glitazones') are effective glucose-lowering agents, but cause weight gain and increase the risk of fracture, while the cardiovascular benefits hoped for in association with 'insulin-sensitization' have not been as expected. Glucagon-like peptide-1 agonists will not be acceptable as initial second-line agents for many people as they are injectable rather than oral. Well-powered 'head-to-head' clinical trials of adequate duration are therefore required to allow evidence-based decisions on second-line therapy.

Original publication




Journal article


QJM : monthly journal of the Association of Physicians

Publication Date





185 - 192


BHF Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK.


Humans, Diabetes Mellitus, Type 2, Weight Gain, Metformin, Sulfonylurea Compounds, Thiazolidinediones, Hypoglycemic Agents, Risk Factors, Drug Synergism, Fractures, Bone, Glucagon-Like Peptide 1, Dipeptidyl-Peptidase IV Inhibitors