Efficacy and tolerability of sitagliptin monotherapy in elderly patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial

Abstract

Objective:

Type 2 diabetes in the elderly is an important and insufficiently studied public health problem. This study evaluated sitagliptin monotherapy in patients with type 2 diabetes aged ≥65 years.

Research design and methods:

This was a randomized, double-blind, placebo-controlled, parallel-group study conducted at 52 sites in the United States. Patients were treated with once-daily sitagliptin (100 or 50 mg, depending on renal function) or placebo for 24 weeks. Key endpoints included change from baseline in glycated hemoglobin (HbA_1c), 2-hour post-meal glucose (2-h PMG) and fasting plasma glucose (FPG) at week 24, and average blood glucose on treatment days 3 and 7.

Clinical trial registration: NCT00305604.

Results:

Among randomized patients (N = 206), mean age was 72 years and mean baseline HbA_1c was 7.8%. At week 24, HbA_1c decreased by 0.7%, 2-h PMG by 61 mg/dL, and FPG by 27 mg/dL in sitagliptin-treated patients compared with placebo (all p < 0.001). On day 3 of treatment, mean average blood glucose was decreased from baseline by 20.4 mg/dL in sitagliptin-treated patients compared with placebo (p < 0.001). In subgroups defined by baseline HbA_1c <8.0% (n = 132), ≥8.0% to <9.0% (n = 42), and ≥9.0% (n = 18), the placebo-adjusted reductions in HbA_1c with sitagliptin treatment were 0.5%, 0.9%, and 1.6%, respectively. Patients in the sitagliptin and placebo groups had similar rates of adverse events overall (46.1% and 52.9%, respectively); serious adverse events were reported in 6.9% and 13.5%, respectively. No adverse events of hypoglycemia were reported. Potential study limitations include a relatively small number of patients with more severe hyperglycemia (HbA_1c ≥9.0%) and the exclusion of patients with severe renal insufficiency.

Conclusion:

In this study, sitagliptin treatment significantly and rapidly improved glycemic measures and was well tolerated in patients aged ≥65 years with type 2 diabetes.

Key words::

• DPP-4 inhibitor
• Elderly
• Glycemic control
• Incretins
• Sitagliptin

Transparency

Declaration of funding

This study was sponsored by Merck & Co., Inc. USA.

Declaration of financial/other relationships

NB has disclosed that he has received honoraria/consulting fees from Merck & Co., Inc. for his services on scientific panels. H.G., E.M.M., S.C., G.T.G., R.B.L., D.W-H., K.D.K., J.M.A., B.J.G., and H.S. have disclosed that they are employees or former employees of Merck & Co., Inc. In addition to more direct forms of compensation, these employees may also hold stock and stock options in Merck & Co., Inc. N.B., D.W-H., K.D.K., and J.M.A. contributed to the study concept and design. E.M.M. and H.S. contributed to the acquisition of subjects and/or data. All authors contributed to the analysis and interpretation of data and to the writing and editing of the manuscript. CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

The authors gratefully acknowledge Dr Anne E. de Papp of Merck & Co., Inc. for her contributions to the conceptualization and design of this study, and the study's primary investigators for their diligent efforts: G.M. Abernathy, O.P. Alvarado, S.L. Aronoff, S. Banarer, C.J. Baumgartner, H. Bays, C.M. Chappel, D.A. Claassen, H. Collins, S.E. Conard, C.N. Corder, P.S. Denker, J.K. Earl, M.N. Feinglos, J. Fidelholtz, R.K. Garcia, J.A. Girgis, D.E. Gorman, R.J. Graf, M.W. Greenwald, P.A. Hartley, K.S. Hershon, M.C. Hess, R.K. Hibbert, B.S. Horowitz, R.K. Ison, S.A. Jabbour, L. Kage, R.A. Kaplan, M.J. Kelly, J.W. Ketchum, J.M. Labuda, A.P. Levine, A.J. Lewin, J.E. Lilijenquist, D.H. Linden, T.W. Littlejohn, L. Wynstock, D.W. McCarty, J.H. Mersey, W.F. Miser, D.A. Montgomery, B.J. Nevins, J.E. Pappas, S. Patel, K.K. Pudi, G.L. Raad, J.B. Rosen, M. Samson, D.R. Schumacher, T.R. Smith, D.H. Sugimoto, C.J. Superczynski, E. Szoke, J.C. Ugarte, M.U. Weerasinghe, R.W. Wentworth, J. West, S.A. Yarows, and B.M. Zamora.

Preliminary reports of data from this study were made at the national scientific meetings of the Gerontological Society of America in National Harbor, Maryland, November 21, 2008 and the American Diabetes Association in New Orleans, Louisiana, June 7, 2009.