Comparing the actions of older and newer therapies on body weight: to what extent should these effects guide the selection of antidiabetic therapy?
BACKGROUND
Type 2 diabetes patients are usually overweight or obese. Further weight gain induced by antidiabetic treatment should be avoided if possible. Much attention has been focussed recently on the potential for GLP-1 mimetics, in particular, to reduce weight.


OBJECTIVE
Effects on weight are but one of several important criteria in selecting antidiabetic therapy, however. This review explores the effects on weight of older classes of antidiabetic agents (metformin, sulfonylureas, thiazolidinediones) and the newer drugs acting via the GLP-1 system. Other aspects of their therapeutic profiles and current therapeutic use are reviewed briefly to place effects on weight within a broader context.


RESULTS
Comparative trials demonstrated weight neutrality or weight reduction with metformin, and weight increases with a sulfonylurea or thiazolidinedione. There was no clinically significant change in weight with DPP-4 inhibitors and a small and variable decrease in weight (about 3 kg or less) with GLP-1 mimetics. Improved clinical outcomes have been demonstrated for metformin and a sulfonylurea (cardiovascular and microvascular benefits, respectively, in the UK Prospective Diabetes Study), and secondary endpoints improved modestly with pioglitazone in the PROactive trial. No outcome benefits have been demonstrated to date with GLP-1-based therapies, and these agents exert little effect on cardiovascular risk factors. Concerns remain over long-term safety of these agents and this must be weighed against any potential benefit on weight management.


CONCLUSIONS
Considering effects on weight within the overall risk-benefit profile of antidiabetic therapies, metformin continues to justify its place at the head of current management algorithms for type 2 diabetes, due to its decades-long clinical evidence base, cardiovascular outcome benefits and low cost.
Bute Medical School, University of St Andrews, St Andrews, Fife, KY16 9TS, UK. jackie.wallace@faht.scot.nhs.uk
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Campbell
D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology*; D003657:Decision Making; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000188:drug therapy; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D052216:Glucagon-Like Peptide 1 / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D054795:Incretins / Q000627:therapeutic use; D009765:Obesity / Q000139:chemically induced / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D054795:Incretins; D052216:Glucagon-Like Peptide 1