Τίτλος:
Efficacy and safety of once-weekly semaglutide 2.0 mg versus 1.0 mg in
patients with type 2 diabetes (SUSTAIN FORTE): a double-blind,
randomised, phase 3B trial
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background Semaglutide is an effective treatment for type 2 diabetes;
however, 20-30% of patients given semaglutide 1.0 mg do not reach
glycaemic treatment goals. We aimed to investigate the efficacy and
safety of once-weekly semaglutide 2.0 mg versus 1.0 mg in adults with
inadequately controlled type 2 diabetes on a stable dose of metformin
with or without a sulfonylurea.
Methods We did a 40-week, randomised, active-controlled, parallel-group,
double-blind, phase 3B trial (SUSTAIN FORTE) at 125 outpatient clinics
in ten countries. Participants (>= 18 years) with inadequately
controlled type 2 diabetes (HbA1c 8.0-10.0%) with metformin and with or
without sulfonylurea were randomly assigned (1:1) by an interactive
web-response system to 2.0 mg or 1.0 mg once-weekly semaglutide.
Participants, site personnel, the clinical study group, and
investigators were masked to the randomised treatment. Outcomes included
change from baseline at week 40 in HbA1c (primary outcome) and
bodyweight (secondary confirmatory outcome), evaluated through trial
product estimand (no treatment discontinuation or without rescue
medication) and treatment policy estimand (regardless of treatment
discontinuation or rescue medication) strategies. This study is
registered with ClinicalTrials.gov, NCT03989232; EudraCT,
2018-004529-96; and WHO, U1111-1224-5162.
Findings Between June 19 and Nov 28, 2019, of 1515 adults assessed for
eligibility, 961 participants (mean age 58.0 years [SD 10.0]; 398
[41%] women) were included. Participants were randomly assigned to
once-weekly semaglutide 2.0 mg (n=480 [50%]) or 1.0 mg (n=481
[50%]); 462 (96%) patients in the semaglutide 2.0 mg group and 471
(98%) in the semaglutide 1.0 mg group completed the trial. Mean
baseline HbA1c was 8.9% (SD 0.6; 73.3 mmol/mol [SD 6.9]) and BMI was
34.6 kg/m2 (SD 7.0). Mean change in HbA1c from baseline at week 40 was
-2.2 percentage points with semaglutide 2.0 mg and -1.9 percentage
points with semaglutide 1.0 mg (estimated treatment difference [ETD]
-0.23 percentage points [95% CI -0.36 to -0.11]; p=0.0003; trial
product estimand) and -2.1 percentage points with semaglutide 2.0 mg and
-1.9 percentage points with semaglutide 1.0 mg (ETD -0.18 percentage
points [-0.31 to -0.04]; p=0.0098; treatment policy estimand). Mean
change in bodyweight from baseline at week 40 was -6.9 kg with
semaglutide 2.0 mg and -6.0 kg with semaglutide 1.0 mg (ETD -0.93 kg
[95% CI -1.68 to -0.18]; p=0.015; trial product estimand) and -6.4 kg
with semaglutide 2.0 mg and -5.6 kg with semaglutide 1.0 mg (ETD -0.77
kg [-1.55 to 0.01]; p=0.054; treatment policy estimand).
Gastrointestinal disorders were the most commonly reported adverse
events (163 [34%] in the 2.0 mg group and 148 [31%] in the 1.0 mg
group). Serious adverse events were similar between treatment groups,
reported for 21 (4%) participants given semaglutide 2.0 mg and 25 (5%)
participants given semaglutide 1.0 mg. Three deaths were reported during
the trial (one in the semaglutide 1.0 mg group and two in the
semaglutide 2.0 mg group).
Interpretation Semaglutide 2.0 mg was superior to 1.0 mg in reducing
HbA1c, with additional bodyweight loss and a similar safety profile.
This higher dose provides a treatment intensification option for
patients with type 2 diabetes treated with semaglutide in need of
additional glycaemic control. Copyright (C) 2021 Elsevier Ltd. All
rights reserved.
Συγγραφείς:
Frias, Juan P.
Auerbach, Pernille
Bajaj, Harpreet S. and
Fukushima, Yasushi
Lingvay, Ildiko
Macura, Stanislava and
Sondergaard, Anette L.
Tankova, I, Tsvetalina
Tentolouris,
Nikolaos
Buse, John B.
Περιοδικό:
The Lancet Diabetes & Endocrinology
Εκδότης:
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
DOI:
10.1016/S2213-8587(21)00174-1
