Treating the Obese Diabetic

Julia Kenkre; Tricia Tan; Stephen Bloom


Expert Rev Clin Pharmacol. 2013;6(2):171-183. 

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Expert Commentary

Faced with a newly diagnosed obese diabetic patient in a real world setting, it is important to ensure that the antidiabetic medications prescribed are effective and safe, without inducing weight gain. Ideally, our therapeutic strategy would utilize treatments with a long-term safety record that can induce weight loss and have been shown to improve CV outcomes. The only two treatments that offer this level of evidence at present are bariatric surgery and metformin.

Bariatric surgery can be seriously considered as a first option as it leads to long-term remission of diabetes in many patients, has been shown to improve mortality and reduces the incidence of CV disease. However, there are no prospective RCTs that provide definitive evidence for this indication. In addition, its costs and requirement for specialist facilities, as well as its significant mortality and complications, also mean that this can never represent the solution for the majority of patients with obesity and diabetes.

Metformin offers the combination of proven efficacy in reducing CV risks, a good safety record and low cost, ensuring that it will have a central place in diabesity treatment. However, the weight loss seen with metformin is relatively minor. The new combination of DPP-IV inhibitors and metformin is a well-tolerated treatment, with some gains to be made in terms of glycemic improvement and weight neutrality, but long-term risks are not known.

GLP-1 analogues are effective in reducing weight and glycemia, and arguably should be considered relatively early in the order of treatments for 'diabesity'. In addition, the combination of GLP-1 analogues with basal insulin allows for achievement of glucose targets with some weight loss. However, there are three stumbling blocks to more widespread GLP-1 analogue treatment: first, the requirement for injections reduces patient acceptability; second, analogues remain relatively expensive; third, their long-term safety and ultimate effects on CV risks remain unclear.

The new antiobesity drugs lorcaserin and topiramate/phentermine, recently licensed in the USA, do have some minor effects on glycemia but we would argue these are not primarily indicated for obese diabetics except as adjuncts to the treatments mentioned above, particularly as side effects remain troublesome in these new drugs. A similar argument would apply to the naltrexone/bupropion combination, should this drug ever be approved.