Treatment of elderly patients with type 2 diabetes mellitus: a systematic review of the benefits and risks of dipeptidyl peptidase-4 inhibitors

Background: Achievement of glycemic control in elderly patients with type 2 diabetes mellitus (DM) is complicated by many factors.

Objective: The aim of this article was to systematically review evidence on the effectiveness of dipeptidyl peptidase-4 (DPP-4) inhibitors (ie, lowering of glycosylated hemoglobin [HbA(1c)]), the risk of hypoglycemia associated with these agents, and the effects of these agents on body weight in elderly patients with type 2 DM.

Methods: The PubMed and Biosis databases were searched for reports of clinical trials and meeting presentations (eg, abstracts, posters) published in English between January 1, 2000, and October 25, 2009, that included elderly patients with type 2 DM who were treated with sitagliptin, saxagliptin, vildagliptin, alogliptin, BI-1356, DSP-7238, or PF-734200. Pharmacokinetic and pharmacodynamic studies were excluded from the review, as were studies that did not specifically provide quantitative clinical data on glycemic parameters or specifically list patients aged ≥65 years.

Results: Eighty-five articles and 5 presentations were identified in the search; of those, 18 articles and 3 presentations were included in the review. These publications described studies of DPP-4 inhibitors administered as monotherapy or in combination with metformin, a thiazolidinedione, glimepiride, glibenclamide, or insulin. Quantitative data indicated that, in these elderly patients (generally defined as ≥65 years of age) with type 2 DM, DPP-4 inhibitors were associated with significant HbA(1c) reductions that ranged from ~0.7% (baseline HbA(1c) = 7.8%; P < 0.001) to 1.2% (baseline HbA(1c) = 8.3%; P < 0.05). Additional studies that did not quantify the number of elderly patients (as would a subanalysis), but did specify that elderly patients were included and that patient age did not influence the results, were incorporated in this review to support the quantitative results. No significant differences were noted in the HbA(1c)-lowering effects of these agents between elderly and younger patients. Less information about the incidence of hypoglycemia or weight gain in elderly patients was reported, but the available results suggested that the risk of hypoglycemia with DPP-4 inhibitors was not significantly different from that with placebo (sitagliptin 50 or 100 mg/d [0%] vs placebo [0%]; saxagliptin 5 mg/d [6.3%] vs placebo [8.0%]; vildagliptin 100 mg/d [2.32 events per patient-year] vs placebo [2.64 events per patient-year]; alogliptin 12.5 mg/d [8.0%] vs placebo [10.5%]) and that these agents were weight neutral (change, ≤0.9 kg).

Conclusions: For elderly patients with type 2 DM, reductions in HbA(1c) after treatment with a DPP-4 inhibitor were not significantly different from those in younger patients. Use of DPP-4 inhibitors in these studies was associated with a low risk of hypoglycemia, and these agents were weight neutral.