Treating the Obese Diabetic

Julia Kenkre; Tricia Tan; Stephen Bloom


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

In This Article

DPP-IV Inhibitors

These drugs inhibit DPP-IV, leading to a rise in endogenous GLP-1 levels, enhanced insulin release and suppression of glucagon secretion.[41] Unlike GLP-1 agonists, they do not slow gastric emptying nor increase satiety. At the time of writing there are currently five marketed DPP-IV inhibitors (sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin) approved in different regions of the world (Table 2).

A recent meta-analysis involving 19 studies looking at DPP-IV inhibitors as a monotherapy and in combination with other oral glucose-lowering agents revealed a similar improvement in glycemic control as TZDs or SUs. Unlike SUs and TZDs, they are weight neutral. There are fewer reported instances of hypoglycemia compared with SUs. They performed worse in terms of bodyweight reduction and glycemic control in comparison to metformin but were associated with fewer gastrointestinal side effects.[15] The most common adverse events seen are mild infection and headache. DPP-IV is widely distributed on numerous cell types, including lymphocytes, and has a role in T-cell activation. Owing to this, there has been concern about DPP-IV inhibition leading to a possible compromise of immune function.[41] While all-cause infection was noted to be increased in a Cochrane review for sitagliptin, the meta-analysis previously quoted did not find the rates of upper respiratory tract infections or urinary tract infections to be increased with DPP-IV inhibitors.[42] Longer term studies will be vital in assessing whether these concerns are valid.