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JAMA. 2016 Mar 1;315(9):898-907. doi: 10.1001/jama.2016.1252.

Effect of Insulin Glargine Up-titration vs Insulin Degludec/Liraglutide on Glycated Hemoglobin Levels in Patients With Uncontrolled Type 2 Diabetes: The DUAL V Randomized Clinical Trial.

Author information

1
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas2Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas.
2
Centro de Investigaciones Metabolicas, Buenos Aires, Argentina.
3
Servicio de Endocrinologia, Hospital Universitario de Monterrey "Dr José Eleuterio-González," Nuevo León, México.
4
Valley Research, Fresno, California.
5
Novo Nordisk A/S, Søborg, Denmark.
6
University of North Carolina School of Medicine, Chapel Hill.

Erratum in

Abstract

IMPORTANCE:

Achieving glycemic control remains a challenge for patients with type 2 diabetes, even with insulin therapy.

OBJECTIVE:

To assess whether a fixed ratio of insulin degludec/liraglutide was noninferior to continued titration of insulin glargine in patients with uncontrolled type 2 diabetes treated with insulin glargine and metformin.

DESIGN, SETTING, AND PARTICIPANTS:

Phase 3, multinational, multicenter, 26-week, randomized, open-label, 2-group, treat-to-target trial conducted at 75 centers in 10 countries from September 2013 to November 2014 among 557 patients with uncontrolled diabetes treated with glargine (20-50 U) and metformin (≥1500 mg/d) with glycated hemoglobin (HbA1c) levels of 7% to 10% and a body mass index of 40 or lower.

INTERVENTIONS:

1:1 randomization to degludec/liraglutide (n = 278; maximum dose, 50 U of degludec/1.8 mg of liraglutide) or glargine (n = 279; no maximum dose), with twice-weekly titration to a glucose target of 72 to 90 mg/dL.

MAIN OUTCOMES AND MEASURES:

Primary outcome measure was change in HbA1c level after 26 weeks, with a noninferiority margin of 0.3% (upper bound of 95% CI, <0.3%). If noninferiority of degludec/liraglutide was achieved, secondary end points were tested for statistical superiority and included change in HbA1c level, change in body weight, and rate of confirmed hypoglycemic episodes.

RESULTS:

Among 557 randomized patients (mean: age, 58.8 years; women, 49.7%), 92.5% of patients completed the trial and provided data at 26 weeks. Baseline HbA1c level was 8.4% for the degludec/liraglutide group and 8.2% for the glargine group. HbA1c level reduction was greater with degludec/liraglutide vs glargine (-1.81% for the degludec/liraglutide group vs -1.13% for the glargine group; estimated treatment difference [ETD], -0.59% [95% CI, -0.74% to -0.45%]), meeting criteria for noninferiority (P < .001), and also meeting criteria for statistical superiority (P < .001). Treatment with degludec/liraglutide was also associated with weight loss compared with weight gain with glargine (-1.4 kg for degludec/liraglutide vs 1.8 kg for glargine; ETD, -3.20 kg [95% CI, -3.77 to -2.64],P < .001) and fewer confirmed hypoglycemic episodes (episodes/patient-year exposure, 2.23 for degludec/liraglutide vs 5.05 for glargine; estimated rate ratio, 0.43 [95% CI, 0.30 to 0.61],P < .001). Overall and serious adverse event rates were similar in the 2 groups, except for more nonserious gastrointestinal adverse events reported with degludec/liraglutide (adverse events, 79 for degludec/liraglutide vs 18 for glargine).

CONCLUSIONS AND RELEVANCE:

Among patients with uncontrolled type 2 diabetes taking glargine and metformin, treatment with degludec/liraglutide compared with up-titration of glargine resulted in noninferior HbA1c levels, with secondary analyses indicating greater HbA1c level reduction after 26 weeks of treatment. Further studies are needed to assess longer-term efficacy and safety.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier: NCT01952145.

PMID:
26934259
DOI:
10.1001/jama.2016.1252
[Indexed for MEDLINE]

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