Effect of saxagliptin as add-on therapy in patients with poorly controlled type 2 diabetes on insulin alone or insulin combined with metformin

Abstract

Objective:

To evaluate efficacy and safety of saxagliptin as add-on therapy in patients with type 2 diabetes (T2D) with inadequate glycemic control on insulin alone or combined with metformin.

Methods:

Adults (n = 455) with HbA_1c 7.5–11% on stable insulin therapy (30–150 U/day ± metformin) for at least 8 weeks were stratified by metformin use and randomly assigned 2:1 to receive saxagliptin 5 mg or placebo once daily for 24 weeks. Patients were to maintain stable insulin doses but these could be decreased to reduce risk of hypoglycemia. Patients with hyperglycemia or substantially increased insulin use were rescued with a flexible insulin regimen and remained in the study. Metformin doses were kept stable. The primary efficacy endpoint was change in HbA_1c from baseline to week 24 (or rescue).

Results:

Patients treated with saxagliptin versus placebo had significantly greater reductions in adjusted mean HbA_1c (difference: −0.41%, p < 0.0001), postprandial glucose (PPG) 180-minute area under the curve (−3829.8 mg·min/dL, p = 0.0011), and 120-minute PPG (−23.0 mg/dL, p = 0.0016) at 24 weeks. Treatment with saxagliptin resulted in similar reductions in HBA_1c relative to placebo, irrespective of metformin treatment. At 24 weeks, difference in adjusted mean fasting plasma glucose for saxagliptin versus placebo was −4.02 mg/dL (p = 0.3958); 17.3% and 6.7% of patients in the saxagliptin and placebo groups, respectively, achieved HbA_1c < 7%. Mean change from baseline in body weight at week 24 was 0.39 kg for saxagliptin and 0.18 kg for placebo. Hypoglycemia was reported in 18.4% and 19.9% of patients in the saxagliptin and placebo groups, respectively (confirmed hypoglycemia: 5.3%, 3.3%). Other adverse events reported in at least 5% of patients were urinary tract infection (saxagliptin, placebo: 5.9%, 6.0%), influenza (3.0%, 6.6%), and pain in extremity (1.6%, 6.0%).

Conclusions:

Saxagliptin 5-mg once-daily add-on therapy improves glycemic control in T2D patients on insulin alone or combined with metformin and is generally well-tolerated.

NCT00757588

Keywords::

• Dipeptidyl peptidase-4 inhibitor – DPP-4 – Hypoglycemia – Insulin – Saxagliptin – Type 2 diabetes

Transparency

Declaration of funding

Funding for the study was provided by Bristol-Myers Squibb and AstraZeneca.

Declaration of financial/other relationships

A.H.B. has disclosed that he received research funding from Bristol-Myers Squibb and AstraZeneca and served on advisory panels and speaker’s bureaus for Bristol-Myers Squibb, AstraZeneca, Merck Sharp & Dohme, and Novartis. B.C. has disclosed that he received research funding from Bristol-Myers Squibb and AstraZeneca and served as a consultant, on advisory panels, and on speaker’s bureaus for Bristol-Myers Squibb, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Novo Nordisk, Roche, Sanofi-Aventis, and Takeda. M.D., D.F., and R.C. have disclosed that they are employees of Bristol-Myers Squibb, and R.C. has disclosed that he is a stock shareholder of Bristol-Myers Squibb.

Acknowledgment

The authors thank Karen May for management of the CV181–057 study protocol and Jia Li for biostatistical assistance (both of Bristol-Myers Squibb). Writing support was provided by Susan Leinbach, Clinical Solutions Group, Inc.; and editorial support was provided by Judy Fallon, Complete Healthcare Communications, Inc. Funding for this study was provided by Bristol-Myers Squibb and AstraZeneca.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed any relevant financial relationships.

The results of this study were presented as a poster at the 71st Scientific Sessions of the American Diabetes Association, San Diego, CA, USA, June 24–28, 2011.