Long-term efficacy of sitagliptin as either monotherapy or add-on therapy to metformin: improvement in glycemic control over 2 years in patients with type 2 diabetes

Abstract

Objective:

To evaluate the efficacy of once daily sitagliptin 100 mg as monotherapy or as add-on to metformin in patients with type 2 diabetes mellitus (T2DM) over 2 years of treatment.

Research design and methods:

The monotherapy analysis used pooled 104 week data from 64 patients in two randomized, double-blind trials evaluating the safety and efficacy of sitagliptin monotherapy. Data used were from patients who were randomized to sitagliptin 100 mg/day, were not on an antihyperglycemic agent at the screening visit, had baseline A1C of 7.0%–10.0%, and had Week 104 A1C measurements. The add-on to metformin analysis used pooled data from 347 patients in two randomized double-blind trials evaluating the safety and efficacy of sitagliptin + metformin combination therapy. Data used were from patients who were randomized to sitagliptin 100 mg/day + metformin ≥1500 mg/day, had baseline A1C of 7%–10%, and had Week 104 A1C measurements. Excluded from either analysis were patients who discontinued prior to 2 years (e.g., due to lack of efficacy, a need for rescue medications, or adverse experiences). Analysis endpoints were A1C, fasting plasma glucose (FPG), HOMA-β, proinsulin/insulin (P/I) ratio, and for monotherapy, 2 hour post-meal plasma glucose (PMG).

Results:

For the pooled monotherapy cohort, after 2 years of treatment, mean A1C, FPG, and 2 hour PMG decreased from baseline values of 7.9%, 156 mg/dL, and 223 mg/dL to 6.9%, 143 mg/dL, and 191 mg/dL, respectively, while HOMA-β increased from 67% to 85% and P/I ratio improved from 0.57 to 0.28. For the pooled add-on to metformin cohort, after 2 years of treatment, mean A1C and FPG decreased from baseline values of 7.7% and 160 mg/dL to 6.9% and 140 mg/dL, respectively, while HOMA-β increased from 50% to 62% and P/I ratio improved from 0.33 to 0.28. These analyses are limited in that only patients who were able to complete 104 weeks of study were included.

Conclusion:

In the subset of patients with T2DM who maintained and completed treatment for 2 years with sitagliptin as monotherapy or as add-on to metformin, improvements in glycemic control and measures of β-cell function were observed over the course of treatment.

Keywords: :

• DPP-4
• Beta-cell function
• HOMA-β
• Incretins
• P/I ratio
• Type 2 diabetes disease progression

Transparency

Declaration of funding

These analyses were funded by Merck Sharp & Dohme Corp., Kenilworth, NJ, USA.

Declaration of financial/other relationships

H.L.K., D.W.-H., L.X., G.T.G., H.W., Q.D., J.R.J., E.A.O’N., K.D.K., S.S.E., and B.J.G. have disclosed that they are employees of Merck & Co., Inc., Kenilworth, NJ, USA, or were at the time this study was conducted.

CMRO peer reviewer 1 has disclosed that he has received grants from Eli Lilly, Boehringer Ingelheim, Janssen and Merck. He has also disclosed that he is a consultant to and on the Speakers’ Bureau of Novo Nordisk, Eli Lilly, Boehringer Ingelheim, Janssen and Merck. CMRO peer reviewer 2 has disclosed that he has received consulting fees or lecture fees from Sanofi, Novo Nordisk, Eli Lilly, GlaxoSmithKline, Astellas, Takeda, Boehringer Ingelheim, Johnson & Johnson, Becton Dickinson, AstraZeneca, Taisho Toyama and Taisho.

Acknowledgments

The authors gratefully acknowledge the assistance of Sheila Erespe at Merck & Co., Inc. in submission of the manuscript.

Previous presentation: Some of the material reported here was presented at the ADA Scientific Sessions, 5–9 June 2009, New Orleans, LA, USA; and at the IDF World Congress, 18–22 October 2009, Montreal, Canada.