Randomized, Double-Blind, Phase 3 Trial of Triple Therapy With Dapagliflozin Add-on to Saxagliptin Plus Metformin in Type 2 Diabetes.

Abstract

OBJECTIVE:

To compare the efficacy and safety of treatment with dapagliflozin versus that with placebo add-on to saxagliptin plus metformin in patients whose type 2 diabetes is inadequately controlled with saxagliptin plus metformin treatment.

RESEARCH DESIGN AND METHODS:

Patients receiving treatment with stable metformin (stratum A) (screening HbA1c level 8.0-11.5% [64-102 mmol/mol]) or stable metformin and a dipeptidyl peptidase-4 (DPP-4) inhibitor (stratum B) (HbA1c 7.5-10.5% [58-91 mmol/mol]) for ≥8 weeks received open-label saxagliptin 5 mg/day and metformin for 16 weeks (stratum A) or 8 weeks (stratum B) (saxagliptin replaced any DPP-4 inhibitor). Patients with inadequate glycemic control (HbA1c 7-10.5% [53-91 mmol/mol]) were randomized to receive placebo or dapagliflozin 10 mg/day plus saxagliptin and metformin. The primary end point was the change in HbA1c from baseline to week 24. Secondary end points included fasting plasma glucose (FPG) level, 2-h postprandial glucose (PPG) level, body weight, and proportion of patients achieving an HbA1c level of <7% (53 mmol/mol).

RESULTS:

Treatment with dapagliflozin add-on to saxagliptin plus metformin resulted in a greater mean HbA1c reduction than placebo (-0.82 vs. -0.10% [-9 vs. -1.1 mmol/mol], P < 0.0001). Significantly greater reductions in FPG level, 2-h PPG level, and body weight were observed, and more patients achieved an HbA1c level of <7% (53 mmol/mol) with treatment with dapagliflozin versus placebo. Adverse events were similar across treatment groups, with a low overall risk of hypoglycemia (∼1%). Genital infections developed in more patients with dapagliflozin treatment (5%) than with placebo (0.6%).

CONCLUSIONS:

Triple therapy with dapagliflozin add-on to saxagliptin plus metformin improves glycemic control and is well tolerated in patients whose type 2 diabetes is inadequately controlled with saxagliptin plus metformin therapy.

• Authors: Chantal Mathieu, Aurelian Emil Ranetti, Danshi Li, Ella Ekholm, William Cook, Boaz Hirshberg, Hungta Chen, Lars Hansen, Nayyar Iqbal
• Journal: Diabetes care (Diabetes Care) Vol. 38 Issue 11 Pg. 2009-17 (Nov 2015) ISSN: 1935-5548 [Electronic] United States
• PMID: 26246458 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Chemical References

• Benzhydryl Compounds
• Blood Glucose
• Dipeptides
• Glucosides
• Hypoglycemic Agents
• dapagliflozin
• Metformin
• saxagliptin
• Adamantane

Topics

• Adamantane (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Adult
• Aged
• Benzhydryl Compounds (administration & dosage, adverse effects)
• Blood Glucose (drug effects, metabolism)
• Diabetes Mellitus, Type 2 (drug therapy, epidemiology)
• Dipeptides (administration & dosage, adverse effects, therapeutic use)
• Double-Blind Method
• Drug Therapy, Combination (methods)
• Female
• Glucosides (administration & dosage, adverse effects)
• Humans
• Hypoglycemia (chemically induced, epidemiology)
• Hypoglycemic Agents (administration & dosage, adverse effects, therapeutic use)
• Male
• Metformin (administration & dosage, adverse effects, therapeutic use)
• Middle Aged
• Treatment Outcome
• Urinary Tract Infections (chemically induced, epidemiology)