DPP-4 Inhibition as a Newly Emerging Therapy for Type 2 Diabetes

Carolyn F Deacon, Jens J Holst
US Endocrinology, 2007;(2):-
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Comparison with Existing Therapies
It is of considerable interest to know how effective DPP-4 inhibitors are compared with existing therapies. Treatment for one year with twice-daily vildagliptin or metformin monotherapy gave sustainable reductions in HbA1c levels (-1% and -1.4%, from baseline 8.7%), although the between-group difference failed to establish non-inferiority of vildagliptin to metformin (see Figure 2). There was no weight gain with vildagliptin (in contrast to modest weight loss with metformin), and while the overall incidence of side effects was similar, there were fewer gastrointestinal side effects with vildagliptin.64

Non-inferiority of vildagliptin to rosiglitazone was established in a 24-week study, with both treatments reducing mean HbA1c levels by 1.1% from baseline (8.7%). In a subset of patients (baseline HbA1c >9%), both drugs were equally effective (reductions of 1.8% (vildagliptin) and 1.9% (rosiglitazone)). Lipid profiles were improved more with vildagliptin, and in contrast to rosiglitazone, where patients gained weight, vildagliptin was weight neutral. The overall incidence of side effects was similar, although the incidence of edema with rosiglitazone was higher (4.9% versus 2.5%).73

In another study, sitagliptin was equally effective as glipizide when either agent was added to on-going metformin (mean HbA1c reductions of 0.7% from baseline, 7.5%), with greater red
ctions at higher baseline (~-0.2% from baseline <7%; ~-1.7% from baseline >9% in both groups). After one year, ~60% of patients in each group achieved target HbA1c levels of <7%, but the incidence of hypoglycemia was higher with glipizide (32%) than sitagliptin (5%).74

DPP-4 inhibitors have not yet been directly compared with the incretin mimetics. Exenatide entered the US market in June 2005 as add-on to existing therapy (metformin, sulfonylurea, or both), while liraglutide is in phase III trials. Combination therapy with exenatide lowers HbA1c levels by ~1.0% from baseline (8.4%) with 44% reaching 7% or below. Body weight is reduced, and both weight loss and glycemic improvements are sustained.75 Liraglutide monotherapy over 14 weeks also reduces HbA1c by up to 1.7% relative to placebo (baseline 8.1–8.5%), with ~50% achieving targets levels ≤7% (versus 8% on placebo). Body weight is also reduced.76

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