ORLANDO, Fla., June 24, 2018 /PRNewswire-USNewswire/
-- People with type 1 diabetes (T1D) who take 200 mg or
400 mg of sotagliflozin in addition to optimized insulin therapy
have statistically lower HbA1c levels and weight, as well as low
incidence of severe hypoglycemia after a year of treatment,
compared to those who take a placebo with optimized insulin,
according to the study, "Fifty-Two-Week Efficacy and Safety of
Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapy
to Insulin in Adults with Type 1 Diabetes (inTandem1)," presented
today at the American Diabetes Association's® (ADA's)
78th Scientific Sessions® at the Orange County Convention Center. The study
results are outlined in detail in an article published online today
in Diabetes Care, the ADA's peer-reviewed research journal
dedicated to diabetes treatment and prevention.
Sotagliflozin is an investigational dual inhibitor of sodium
glucose transport proteins 1 and 2 (SGLT1 and SGLT2)—two proteins
responsible for glucose regulation. Inhibition of SGLT1 delays and
reduces glucose absorption in the proximal intestine, improving
postprandial (post meal) glycemic control. SGLT2 inhibition results
in loss of glucose into the urine. Sotagliflozin is the first dual
SGLT1/SGLT2 inhibitor to be extensively studied in humans.
The inTandem1 study, a double-blind, phase 3 trial conducted at
75 sites in the U.S. and Canada,
compared the safety and efficacy of two different doses of oral
sotagliflozin—each used in addition to optimized insulin—to
optimized insulin alone. The study enrolled a total of 793 adults
with T1D who used an insulin pump or were on multiple-injection
therapy (meaning they used one or two injections of long-acting
insulin along with injections of rapid or short-acting insulin
before each meal throughout a 24-hour period). The participants had
HbA1c levels between 7.0 and 11 percent prior to the study. After
six weeks of insulin optimization, participants were randomly
assigned to one of three groups: 268 received a placebo; 263
received 200 mg of sotagliflozin; and 262 received 400 mg of
sotagliflozin, each taken once daily before the first meal of the
day.
In 2017, a comparison of the treatment groups after 24 weeks was
reported, and the results for the primary endpoints of inTandem 1,
2 and 3 were disclosed. After 24 weeks, HbA1c levels, body weight
and systolic blood pressure were significantly reduced with
sotagliflozin added to optimized insulin compared to optimized
insulin alone.
This latest study investigated the effects of the treatment for
a total of 52 weeks and evaluated change in average blood glucose
(HbA1c levels) and body weight, as well as safety. After 52 weeks,
patients who received sotagliflozin in addition to optimized
insulin had sustained reduction in HbA1c levels and body weight,
and lower total daily insulin dose compared to optimized insulin
alone.
Sotagliflozin use was also associated with fewer low blood
glucose events requiring assistance (severe hypoglycemia), despite
lower average blood glucose. A total of 17 participants, each from
the 200 mg sotagliflozin and 400 mg groups (6.5 percent from each
group), reported episodes of severe hypoglycemia compared to 26
participants (9.7 percent) from the placebo group, who reported
severe hypoglycemia events.
Researchers noted that there is an increased risk of diabetic
ketoacidosis (DKA) through SGLT2 inhibition, and the study results
showed that DKA was seen in a greater proportion of patients
treated with sotagliflozin added to optimized insulin than those
patients treated with optimized insulin alone. Of the participants,
nine patients (3.4 percent) from the 200 mg group and 11 patients
(4.2 percent) in the 400 mg group experienced DKA compared to one
patient (0.4 percent) from the placebo group. According to the
study authors, this increased risk of DKA could potentially be
managed with patient education and increased monitoring.
Overall, the data indicated that more of the patients taking
sotagliflozin added to optimized insulin therapy achieved the
combined goal (the net clinical benefit) of an average blood
glucose below the ADA-recommended target without severe
hypoglycemia and without DKA. For net clinical benefit, 69 patients
(26.2 percent) from the 200 mg group and 85 (32.4 percent) from the
400 mg group achieved this endpoint compared to 51 (19 percent)
from the placebo group at 52 weeks.
"More than 1.25 million adults in the U.S. live with T1D, and
more than 75 percent of these people who use insulin alone have
blood glucose levels above target," said lead study investigator
John Buse, MD, PhD, director of the
Diabetes Center, director of the NC Translational and Clinical
Sciences Institute, and executive associate dean for clinical
research at the University of North
Carolina School of Medicine in Chapel Hill. "Despite recent advances, the
challenges of T1D management, specifically hypoglycemia or fear of
hypoglycemia, weight gain, glucose variability and patient burden,
prevent many patients from reaching their treatment goals. The
profile of sotagliflozin to improve glucose control beyond what can
be achieved with intensified insulin alone while addressing these
challenges has the potential to improve the lives of people with
T1D."
To speak with Dr. Buse, please contact the ADA Press Office
on-site at the Orange County
Convention Center on June 22 - 26, by
phone at 407-685-4010 or by email at press@diabetes.org.
The American Diabetes Association's 78th Scientific Sessions, to
be held June 22-26, 2018, at the
Orange County Convention Center in
Orlando, is the world's largest
scientific meeting focused on diabetes research, prevention and
care. During the five-day meeting, more than 16,000 health care
professionals from around the world will have exclusive access to
more than 3,000 original diabetes research presentations,
participate in provocative and engaging exchanges with leading
diabetes experts, and can earn Continuing Medical Education (CME)
or Continuing Education (CE) credits for educational sessions. The
program is grouped into eight theme areas: Acute and Chronic
Complications; Behavioral Medicine, Clinical Nutrition, Education
and Exercise; Clinical Diabetes/Therapeutics;
Epidemiology/Genetics; Immunology/Transplantation; Insulin
Action/Molecular Metabolism; Integrated Physiology/Obesity; and
Islet Biology/Insulin Secretion. Felicia
Hill-Briggs, PhD, ABPP, President of Health Care and
Education, will deliver her address, "The American Diabetes
Association in the Era of Health Care Transformation," on
Saturday, June 23, and Jane E.B. Reusch, MD, President of Medicine and
Science, will present her address, "24/7/365 – Lifetime with
Diabetes," on Sunday, June 24. In
total, the 2018 Scientific Sessions includes 375 oral
presentations; 2,117 poster presentations, including 47 moderated
poster discussions; and 297 published-only abstracts. Join the
Scientific Sessions conversation on social media using
#2018ADA.
About the American Diabetes Association
Nearly half of
American adults have diabetes or prediabetes; more than 30 million
adults and children have diabetes; and every 21 seconds, another
individual is diagnosed with diabetes in the U.S. Founded in 1940,
the American Diabetes Association (ADA) is the nation's leading
voluntary health organization whose mission is to prevent and cure
diabetes, and to improve the lives of all people affected by
diabetes. The ADA drives discovery by funding research to treat,
manage and prevent all types of diabetes, as well as to search for
cures; raises voice to the urgency of the diabetes epidemic; and
works to safeguard policies and programs that protect people with
diabetes. In addition, the ADA supports people living with
diabetes, those at risk of developing diabetes, and the health care
professionals who serve them through information and programs that
can improve health outcomes and quality of life. For more
information, please call the ADA at 1-800-DIABETES (1-800-342-2383)
or visit diabetes.org. Information from both of these sources is
available in English and Spanish. Find us on Facebook (American
Diabetes Association), Twitter (@AmDiabetesAssn) and Instagram
(@AmDiabetesAssn).
212-OR
|
Fifty-Two-Week
Efficacy and Safety of Sotagliflozin, a Dual SGLT1 and SGLT2
Inhibitor, as
Adjunct Therapy to Insulin in Adults with Type 1 Diabetes
(inTandem1)
|
78th Scientific Sessions
News
Briefing: Adjunctive Therapies in Type 1 and Type 2
Diabetes, Sunday, June 24,
7:15 a.m., ET
Session Type: Oral Presentations
Session Title: Clinical Trials in Type 1 Diabetes
Location: W308
Session Time: Sunday, June 24, 2018,
2:15 pm - 4:15 pm
JOHN B. BUSE, SATISH K. GARG, JULIO
ROSENSTOCK, TIMOTHY S.
BAILEY, PHILLIP L. BANKS,
BRUCE W. BODE, THOMAS DANNE, JAKE A.
KUSHNER, WENDY LANE,
PABLO LAPUERTA, DARREN K. MCGUIRE, ANNE
L. PETERS, JOHN H. REED,
SANGEETA SAWHNEY, PAUL STRUMPH, Chapel
Hill, NC, Aurora, CO,
Dallas, TX, Escondido, CA, The
Woodlands, TX, Atlanta, GA,
Hannover, Germany, Houston, TX, Asheville, NC, Basking Ridge, NJ, Los Angeles, CA, Roswell, GA
Sotagliflozin (SOTA) is a dual SGLT1 and SGLT2 inhibitor in
development as adjunct therapy to insulin in T1D. In this
double-blind, 52-week North American trial, 793 adults with T1D
treated with multiple daily insulin injections (40%) or pump (60%)
were randomized 1:1:1 to placebo (n=268), SOTA 200 mg (n=263) or
SOTA 400 mg (n=262) once daily after 6 weeks of insulin
optimization. Primary endpoint was change from baseline in A1C at
Week 24. Other endpoints included A1C, weight, bolus insulin and
FPG changes at Week 52, patient (pt) reported outcomes and net
clinical benefit (NCB), assessing the proportion of pts with A1C
<7.0% without severe hypoglycemia (SH) or diabetic ketoacidosis
(DKA).
Baseline characteristics were similar between groups. Compared
with placebo, SOTA 200 and 400 mg improved A1C and pt satisfaction
at Week 24 and reduced A1C, weight, bolus insulin, FPG and pt
distress at Week 52. More pts achieved NCB with SOTA vs. placebo
(each P<0.05; Table). The highest incidence of SH was in the
placebo arm; more genital mycotic infections, diarrhea and DKA
events (more with pump than MDI) were in the SOTA arms (Table).
In conclusion, SOTA 200 and 400 mg were associated with
statistically significant A1C reductions that were sustained
(P<0.05) at Week 52, with an increased (but low) rate of DKA,
and a lower incidence of SH, when compared with placebo.
Efficacy (mITT
population) and Safety (safety population) Results
|
|
Placebo
n=268
|
SOTA 200
mg
n=263
|
SOTA 400
mg
n=262
|
Mean A1C at Baseline,
after 6-week insulin
optimization, %
|
7.54
|
7.61
|
7.56
|
Outcomes at Week
24
|
A1C LSM difference
from placebo, % ± SE (P-
value)
|
-
|
-0.36±0.05(<0.001)
|
-0.41±0.05
(<0.001)
|
Outcomes at Week
52
|
A1C LSM difference
from placebo, % ± SE (P-value)
|
-
|
-0.25±0.06
(P<0.001)
|
-0.31±0.06
(P<0.001)
|
FPG LSM difference
from placebo, mmol/L ±
SE
|
-
|
-0.68±0.31
(P=0.028)
|
-1.08±0.31
(P<0.001)
|
Body weight LSM
difference from placebo,
kg ± SE (P-value)
|
-
|
-3.14±0.34
(P<0.001)
|
-4.32±0.35
(P<0.001)
|
Mean daily bolus
insulin dose at Baseline, IU
|
31.7
|
30.3
|
30.8
|
Bolus insulin dose
mean change from
Baseline, % ± SE
|
7.01±3.40
|
-1.48±3.40
|
-8.63±3.42
|
Bolus insulin dose
LSM difference from
placebo, % ± SE (P-value)
|
-
|
-5.53±4.59
(P=0.23)
|
-15.63±4.60
(P<0.001)
|
Net clinical
benefit at Week 52
|
A1C <7.0% without
SH and without DKA, n
(%)
|
51 (19.0)
|
69 (26.2)
|
85 (32.4)
|
Safety outcomes
over 52 weeks
|
Any TEAE, n
(%)
|
216 (80.6)
|
215 (81.7)
|
209 (79.8)
|
TEAEs leading to
study discontinuation, n
(%)
|
11 (4.1)
|
13 (4.9)
|
17 (6.5)
|
Treatment-emergent
serious adverse
events, n (%)
|
20 (7.5)
|
27 (10.3)
|
29 (11.1)
|
Death, n
(%)
|
1 (0.4)
|
0
|
0
|
DKA, n
(%)1
|
1 (0.4)
|
9 (3.4)
|
11 (4.2)
|
Severe hypoglycemia,
n (%)1
|
26 (9.7)
|
17 (6.5)
|
17 (6.5)
|
Diarrhea2,
n (%)
|
18 (6.7)
|
22 (8.4)
|
27 (10.3)
|
Genital mycotic
infection, n (%)
|
9 (3.4)
|
24 (9.1)
|
34 (13.0)
|
Patient reported
outcomes
|
DTSQ score LSM
difference from placebo at
Week 24 ± SE (P-value)
|
-
|
2.5±0.40
(P<0.001)
|
2.5±0.40
(P<0.001)
|
DDS2 score LSM
difference from placebo at
Week 52 ± SE (P-value)
|
-
|
-0.4±0.15
(P=0.003)
|
-0.5±0.15
(P<0.001)
|
DDS2, two-item
Diabetes Distress Screening Scale (positive scores indicate
improvement); DKA, diabetic
ketoacidosis; DTSQ, diabetes treatment satisfaction questionnaire;
FPG, fasting plasma glucose; LSM,
least squares mean; mITT, modified intent-to-treat; SD, standard
deviation; SE, standard error; SH, severe
hypoglycemia; SOTA, sotagliflozin; TEAE, treatment emergent adverse
events. 1Positively-adjudicated
events (defined as an adjudicator assessment of yes/certainly or
yes/probably); 2Discontinuation of drug
due to diarrhea was: 0.4% placebo, 0% SOTA 200 mg, and 0.4% SOTA
400 mg.
|
Author Disclosures: J.B. Buse: Other Relationship; Self;
ADOCIA, AstraZeneca, Dexcom, Inc., Elcelyx Therapeutics, Inc., Eli
Lilly and Company, Fractyl Laboratories, Inc., Intarcia
Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Metavention,
NovaTarg, Novo Nordisk A/S, Sanofi, VTV Therapeutics. Research
Support; Self; Boehringer Ingelheim GmbH, Johnson & Johnson
Services, Inc., Theracos, Inc.. Other Relationship; Self; Shenzhen
Hightide Biopharmaceutical, Ltd.. Research Support; Self; National
Heart, Lung, and Blood Institute, National Center for Advancing
Translational Sciences. Other Relationship; Self; National
Institute of Diabetes and Digestive and Kidney Diseases, American
Diabetes Association. Research Support; Self; Patient-Centered
Outcomes Research Institute. Other Relationship; Self; National
Institute of Environmental Health Sciences. S.K. Garg: Research
Support; Self; Dexcom, Inc., Eli Lilly and Company, Sanofi US.
Advisory Panel; Self; Sanofi US. Research Support; Self; MannKind
Corporation, Diasome Pharmaceuticals, Inc., Labstyle Innovations,
Lexicon Pharmaceuticals, Inc., Medtronic. Advisory Panel; Self;
Novo Nordisk A/S. J. Rosenstock: Advisory Panel; Self; Eli Lilly
and Company. Consultant; Self; Eli Lilly and Company. Research
Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk
Inc.. Advisory Panel; Self; Sanofi. Consultant; Self; Sanofi.
Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Consultant;
Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self;
Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self;
Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self;
Intarcia Therapeutics, Inc.. Consultant; Self; Intarcia
Therapeutics, Inc.. Research Support; Self; Merck & Co., Inc.,
Pfizer Inc., Sanofi, Novo Nordisk Inc., Bristol-Myers Squibb
Company, Eli Lilly and Company, Intarcia Therapeutics, Inc.,
Genentech, Inc. T.S. Bailey: Research Support; Self; Abbott. Consultant; Self; Abbott. Speaker's Bureau; Self; Abbott. Research Support; Self; Ambra
BioScience, Ascensia Diabetes Care, Becton, Dickinson and Company. Consultant; Self;
Becton, Dickinson and Company.
Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.,
Calibra Medical. Consultant; Self; Calibra Medical. Research
Support; Self; Companion Medical, Dexcom, Inc., Glooko, Inc.,
GlySens Incorporated, Lexicon Pharmaceuticals, Inc., Eli Lilly and
Company. Consultant; Self; Eli Lilly and Company. Speaker's Bureau;
Self; Eli Lilly and Company. Research Support; Self; Medtronic
MiniMed, Inc.. Consultant; Self; Medtronic MiniMed, Inc.. Speaker's
Bureau; Self; Medtronic MiniMed, Inc.. Research Support; Self; Novo
Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Speaker's
Bureau; Self; Novo Nordisk Inc.. Research Support; Self; Sanofi.
Consultant; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research
Support; Self; Senseonics. Consultant; Self; Intarcia Therapeutics,
Inc.. Research Support; Self; Versartis, Inc., Xeris
Pharmaceuticals, Inc., MannKind Corporation. P.L. Banks: Employee;
Self; Lexicon Pharmaceuticals, Inc. B.W. Bode: Research Support;
Self; Abbott. Advisory Panel;
Self; ADOCIA. Research Support; Self; Boehringer Ingelheim
Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals,
Inc.. Research Support; Self; GlaxoSmithKline plc., Lexicon
Pharmaceuticals, Inc., Medtronic MiniMed, Inc., Novo Nordisk Inc.,
Diasome Pharmaceuticals, Inc., Sanofi US, Eli Lilly and Company,
MannKind Corporation, Dexcom, Inc., OmniPod, Senseonics. T. Danne:
Speaker's Bureau; Self; A. Menarini Diagnostics. Advisory Panel;
Self; Abbott, AstraZeneca, Bayer
AG, Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Dexcom,
Inc.. Research Support; Self; Eli Lilly and Company.
Stock/Shareholder; Self; DreaMed Diabetes, Ltd.. Research Support;
Self; Insulet Corporation. Speaker's Bureau; Self; Menarini Group.
J.A. Kushner: Advisory Panel; Self; Lexicon Pharmaceuticals, Inc..
Consultant; Self; KNOW Foods, Inc. W. Lane: Advisory Panel; Self;
Novo Nordisk A/S, Insulet Corporation, Intarcia Therapeutics, Inc.,
Sanofi. Research Support; Self; Novo Nordisk A/S, Eli Lilly and
Company, Lexicon Pharmaceuticals, Inc., Sanofi, Dexcom, Inc..
Speaker's Bureau; Self; Novo Nordisk A/S, Insulet Corporation. P.
Lapuerta: Employee; Self; Lexicon Pharmaceuticals, Inc..
Stock/Shareholder; Self; Lexicon Pharmaceuticals, Inc., Merck &
Co., Inc. D.K. McGuire: Consultant; Self; AstraZeneca,
Sanofi-Aventis, Eli Lilly and Company, Boehringer Ingelheim
Pharmaceuticals, Inc., Merck & Co., Inc., Pfizer Inc., Novo
Nordisk A/S. Research Support; Self; AstraZeneca, Sanofi-Aventis,
Janssen Pharmaceuticals, Inc., Boehringer Ingelheim
Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S,
Lexicon Pharmaceuticals, Inc., Eisai Inc., GlaxoSmithKline plc.,
Esperion Therapeutics. A.L. Peters:Advisory Panel; Self;
Abbott, Bigfoot Biomedical.
Research Support; Self; Dexcom, Inc.. Advisory Panel; Self; Eli
Lilly and Company, Insulin Algorithms, JDRF, Lexicon
Pharmaceuticals, Inc., Livongo Health. Research Support; Self;
MannKind Corporation. Other Relationship; Self; Medscape. Advisory
Panel; Self; Merck & Co., Inc.. Research Support; Self;
National Institute of Diabetes and Digestive and Kidney Diseases.
Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self;
Novo Nordisk Inc., Omada Health, Inc., Optum Rx, Inc., Sanofi.
Research Support; Self; T1D Exchange. Advisory Panel; Self; The
Endocrine Society. Research Support; Self; The Leona M. and Harry
B. Helmsley Charitable Trust. Advisory Panel; Spouse/Partner;
Johnson & Johnson Diabetes Institute, LLC.. J.H. Reed: None. S.
Sawhney: Employee; Self; Lexicon Pharmaceuticals, Inc..
Stock/Shareholder; Spouse/Partner; GlaxoSmithKline plc.,
AstraZeneca, Pfizer Inc., Eli Lilly and Company, Novartis
Pharmaceuticals Corporation. P. Strumph: Employee; Self; Lexicon
Pharmaceuticals, Inc.. Stock/Shareholder; Self; Lexicon
Pharmaceuticals, Inc.. Board Member; Self; College Diabetes
Network.
Press Office in Orlando
June 22 - 26, 2018
407-685-4010
Contact:
Michelle Kirkwood
(703) 299-2053
mkirkwood@diabetes.org
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SOURCE American Diabetes Association