The efficacy and safety of the dipeptidyl peptidase-4 inhibitor saxagliptin in treatment-naïve patients with type 2 diabetes mellitus: a randomized controlled trial

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

The aim of this study was to assess efficacy and safety of saxagliptin monotherapy for up to 76 weeks in patients with type 2 diabetes mellitus (T2DM) and inadequate glycemic control, with main efficacy assessment at 24 weeks.

Methods

365 treatment-naïve patients with T2DM (HbA _1c 7.0%–10.0%) were treated with saxagliptin 2.5 mg q.A.M., saxagliptin 2.5 mg q.A.M. with possible titration to saxagliptin 5 mg, saxagliptin 5 mg q.A.M., saxagliptin 5 mg q.P.M., or placebo. After week 24, patients in all groups were eligible for titration to saxagliptin 10 mg based on HbA _1c ≥7%, and all unrescued placebo patients began blinded metformin 500 mg/day. Rescue with open-label metformin was available for patients with inadequate glycemic control.

Results

At week 24, placebo-subtracted mean HbA _1c reduction from baseline (LOCF) was significantly greater in the saxagliptin treatment groups vs placebo, and remained greater through week 76. Serious adverse events (AEs) and discontinuations due to AEs were similar in saxagliptin and control groups; incidence of confirmed hypoglycemia was low across all treatment groups (saxagliptin-treated, 2 [0.7]; control, 1 [1.4]).

Conclusions

In treatment-naïve patients with T2DM, saxagliptin monotherapy demonstrated statistically significant improvement in HbA _1c compared with placebo at 24 weeks and was generally well tolerated for up to 76 weeks.

Trial registration

ClinicalTrials.gov Identifier: NCT00316082

Related collections

Most cited references 12

Record: found
Abstract: found
Article: not found

U.K. prospective diabetes study 16. Overview of 6 years' therapy of type II diabetes: a progressive disease. U.K. Prospective Diabetes Study Group.

UK Prospective Diabetes (1995)

The objective of the U.K. Prospective Diabetes Study is to determine whether improved blood glucose control in type II diabetes will prevent the complications of diabetes and whether any specific therapy is advantageous or disadvantageous. The study will report in 1998, when the median duration from randomization will be 11 years. This report is on the efficacy of therapy over 6 years of follow-up and the overall incidence of diabetic complications. Subjects comprised 4,209 newly diagnosed type II diabetic patients who after 3 months' diet were asymptomatic and had fasting plasma glucose (FPG) 6.0-15.0 mmol/l. The study consists of a randomized controlled trial with two main comparisons: 1) 3,867 patients with 1,138 allocated to conventional therapy, primarily with diet, and 2,729 allocated to intensive therapy with additional sulfonylurea or insulin, which increase insulin supply, aiming for FPG < 6 mmol/l; and 2) 753 obese patients with 411 allocated to conventional therapy and 342 allocated to intensive therapy with metformin, which enhances insulin sensitivity. In the first comparison, in 2,287 subjects studied for 6 years, intensive therapy with sulfonylurea and insulin similarly improved glucose control compared with conventional therapy, with median FPG at 1 year of 6.8 and 8.2 mmol/l, respectively (P < 0.0001). and median HbA1c of 6.1 and 6.8%, respectively (P < 0.0001). During the next 5 years, the FPG increased progressively on all therapies (P < 0.0001) with medians at 6 years in the conventional and intensive groups, FPG 9.5 and 7.8 mmol/l, and HbA1c 8.0 and 7.1%, respectively. The glycemic deterioration was associated with progressive loss of beta-cell function. In the second comparison, in 548 obese subjects studied for 6 years, metformin improved glucose control similarly to intensive therapy with sulfonylurea or insulin. Metformin did not increase body weight or increase the incidence of hypoglycemia to the same extent as therapy with sulfonylurea or insulin. A high incidence of clinical complications occurred by 6-year follow-up. Of all subjects, 18.0% had suffered one or more diabetes-related clinical endpoints, with 12.1% having a macrovascular and 5.7% a microvascular endpoint. Sulfonylurea, metformin, and insulin therapies were similarly effective in improving glucose control compared with a policy of diet therapy. The study is examining whether the continued improved glucose control, obtained by intensive therapy compared with conventional therapy (median over 6 years HbA1c 6.6% compared with 7.4%), will be clinically advantageous in maintaining health.

0 comments Cited 235 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology Consensus Panel on Type 2 Diabetes Mellitus: An Algorithm for Glycemic Control

Helena Rodbard, Paul S. Jellinger, Jaime Davidson … (2009)

This report presents an algorithm to assist primary care physicians, endocrinologists, and others in the management of adult, nonpregnant patients with type 2 diabetes mellitus. In order to minimize the risk of diabetes-related complications, the goal of therapy is to achieve a hemoglobin A1c (A1C) of 6.5% or less, with recognition of the need for individualization to minimize the risks of hypoglycemia. We provide therapeutic pathways stratified on the basis of current levels of A1C, whether the patient is receiving treatment or is drug naïve. We consider monotherapy, dual therapy, and triple therapy, including 8 major classes of medications (biguanides, dipeptidyl-peptidase-4 inhibitors, incretin mimetics, thiazolidinediones, alpha-glucosidase inhibitors, sulfonylureas, meglitinides, and bile acid sequestrants) and insulin therapy (basal, premixed, and multiple daily injections), with or without orally administered medications. We prioritize choices of medications according to safety, risk of hypoglycemia, efficacy, simplicity, anticipated degree of patient adherence, and cost of medications. We recommend only combinations of medications approved by the US Food and Drug Administration that provide complementary mechanisms of action. It is essential to monitor therapy with A1C and self-monitoring of blood glucose and to adjust or advance therapy frequently (every 2 to 3 months) if the appropriate goal for each patient has not been achieved. We provide a flow-chart and table summarizing the major considerations. This algorithm represents a consensus of 14 highly experienced clinicians, clinical researchers, practitioners, and academicians and is based on the American Association of Clinical Endocrinologists/American College of Endocrinology Diabetes Guidelines and the recent medical literature.

0 comments Cited 187 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Effect of saxagliptin monotherapy in treatment-naïve patients with type 2 diabetes.

J List, Patricia Klein, Hector Aguilar … (2009)

To evaluate the efficacy and safety of once-daily saxagliptin monotherapy in treatment-naïve patients with type 2 diabetes (T2D) and inadequate glycemic control. This study included a main treatment cohort (MTC) with 401 patients (HbA(1c) > or = 7% and 10% and < or =12%) who received saxagliptin 10 mg once daily for 24 weeks. Primary endpoint was HbA(1c) change from baseline to week 24. Secondary endpoints included change from baseline to week 24 in fasting plasma glucose (FPG), proportion of patients achieving HbA(1c) < 7%, and changes in postprandial glucose area-under-the-curve (PPG-AUC). Efficacy analyses for continuous variables were performed using an ANCOVA model with last-observation-carried-forward methodology. In the MTC, saxagliptin demonstrated statistically significant decreases in adjusted mean HbA(1c) changes from baseline (mean, 7.9%) to week 24 (-0.43%, -0.46%, -0.54%) for saxagliptin 2.5, 5, and 10 mg, respectively, vs. +0.19% for placebo (all p < 0.0001). Adjusted mean FPG was significantly reduced from baseline (-15, -9, -17 mg/dL) for saxagliptin 2.5, 5, and 10 mg, respectively, vs. +6 mg/dL for placebo (p = 0.0002, p = 0.0074, p < 0.0001, respectively). More saxagliptin-treated patients achieved HbA(1c) < 7% at week 24 (35% [p = NS], 38% [p = 0.0443], 41% [p = 0.0133]) for saxagliptin 2.5, 5, and 10 mg, respectively, than placebo (24%). PPG-AUC was reduced for saxagliptin 2.5, 5, and 10 mg (-6868, -6896, -8084 mg x min/dL, respectively) vs. placebo (-647 mg x min/dL) with statistical significance demonstrated for saxagliptin 5 mg (p = 0.0002) and 10 mg (p < 0.0001). HbA(1c), FPG, and PPG-AUC reductions were also observed in the OLC at 24 weeks. In the MTC, adverse event frequency was similar across all study arms. No cases of confirmed hypoglycemia (symptoms, with fingerstick glucose < or =50 mg/dL) were observed in either cohort. Saxagliptin was not associated with weight gain. Study limitations included the lack of a control group for the OLC and the use of prespecified rescue criteria, which limited the exposure time during which patients could remain on their originally randomized medication without the introduction of additional antihyperglycemic rescue treatment. Once-daily saxagliptin monotherapy for 24 weeks was generally well tolerated and demonstrated clinically meaningful reductions in key parameters of glycemic control vs. placebo. Clinical Trials NCT00121641

0 comments Cited 67 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Diabetol Metab Syndr

Journal ID (iso-abbrev): Diabetol Metab Syndr

Title: Diabetology & Metabolic Syndrome

Publisher: BioMed Central

ISSN (Electronic): 1758-5996

Publication date Collection: 2012

Publication date (Electronic): 24 July 2012

Volume: 4

Page: 36

Affiliations

[1 ]Bristol-Myers Squibb, Route 206 & Province Line Road, Princeton, NJ, 08543, USA

[2 ]PMG Research of Salisbury, 401 Mocksville Ave., Salisbury, NC, 28144, USA

[3 ]AstraZeneca R&D, Kärragatan 5, 431 83, Mölndal, Sweden

Article

Publisher ID: 1758-5996-4-36

DOI: 10.1186/1758-5996-4-36

PMC ID: 3541110

PubMed ID: 22828124

SO-VID: 4f69b4e6-a2c4-4e53-ac3f-0f9e19dc7a95

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The efficacy and safety of the dipeptidyl peptidase-4 inhibitor saxagliptin in treatment-naïve patients with type 2 diabetes mellitus: a randomized controlled trial

Read this article at

Abstract

Background

Methods

Results

Conclusions

Trial registration

Related collections

Karger: Nutrition and Dietetics

Most cited references 12

U.K. prospective diabetes study 16. Overview of 6 years' therapy of type II diabetes: a progressive disease. U.K. Prospective Diabetes Study Group.

Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology Consensus Panel on Type 2 Diabetes Mellitus: An Algorithm for Glycemic Control

Effect of saxagliptin monotherapy in treatment-naïve patients with type 2 diabetes.

Author and article information

Journal

Affiliations

Article

History

Categories

Comments

Comment on this article

Similar content 204

Cited by 19

Most referenced authors 1,039