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ORLANDO, Fla., June 24, 2018 /PRNewswire-USNewswire/ -- Adding the selective SGLT2 inhibitor dapagliflozin to intensive insulin therapy in adults with type 1 diabetes (T1D) who had sub-optimal glycemic control reduced blood glucose levels, aided in weight loss and led to a reduction in insulin doses, yet also correlated with a slight increase in diabetic ketoacidosis risk compared to placebo, according to the study "Efficacy and Safety of Dapagliflozin in Patients with Inadequately Controlled Type 1 Diabetes—DEPICT-2 Study," presented today at the American Diabetes Association's^® (ADA's) 78th Scientific Sessions^® at the Orange County Convention Center Convention Center..

Dapagliflozin is a selective inhibitor of SGLT2—a protein responsible for glucose regulation. SGLT2 inhibitors block the SGLT2 protein involved in glucose reabsorption in the proximal renal tubule of the kidney, which results in an increase in renal glucose excretion and lower blood glucose levels.

DEPICT-2 was a phase 3, double-blind, global study conducted among 137 sites in North America, South America, Europe and Asia to evaluate the efficacy and safety of dapagliflozin as an add-on to insulin therapy in people with T1D. The trial was similar in design to the DEPICT-1 study, which was published in September 2017.

DEPICT-2 enrolled 813 adults between the ages of 18 and 75 with T1D who had an HbA1c level from 7.5 to 10.5 percent. Patients were randomly assigned to receive daily, oral doses of either 5 mg of dapagliflozin (271 patients), 10 mg of dapagliflozin (270 patients) or a placebo (272 patients), in addition to their usual insulin, for 52 weeks. The insulin dose could be adjusted by clinicians based on the patient's self-monitored blood glucose readings, local guidance and individual circumstances.

This study evaluated patients after 24 weeks on the regimen, and the results showed that compared to placebo, patients treated with 5 mg and 10 mg of dapagliflozin had a decrease in HbA1c levels by .37 to .42 percent, respectively. The addition of dapagliflozin was also accompanied by weight loss, with the patients on 5 mg losing an average of 3.2 percent of their body weight, and the patients who received 10 mg losing 3.7 percent of their body weight, compared to an average weight loss of .02 percent in the placebo group. There was also a reduction in insulin doses in the dapagliflozin 5 mg and 10 mg group (-10.78 percent to -11.08 percent, compared to placebo). Continuous glucose monitoring showed more improved, stable glycemic values among dapagliflozin-treated patients, leading to an increased time-in-range over 24 hours of 2h 10min with dapagliflozin 5mg, and a little over 2h 30min with dapagliflozin 10mg, compared to placebo.

The safety analysis showed no significant increased risk of hypoglycemia, and in particular, severe hypoglycemia among patients treated with dapagliflozin: 17 patients (6.3 percent) from the dapagliflozin 5 mg group, 23 patients (8.5 percent) from the dapagliflozin10 mg group, and 21 patients (7.7 percent) from the placebo group experienced one or more episodes of severe hypoglycemia over the 24-week period. However, the dapagliflozin patients did have an increased risk of diabetic ketoacidosis (DKA), a known complication for patients with diabetes that affects those with type 1 diabetes more frequently than patients with type 2 diabetes. No patients from the placebo group experienced DKA, compared to 2.6 percent for the dapagliflozin 5 mg group and 2.2 percent for the dapagliflozin10 mg group.

"The results of our study add to a growing body of evidence showing that SGLT2 inhibitors have the potential to serve as promising adjunct therapies in people with T1D who are not consistently in their target blood glucose range," said Chantal Mathieu, MD, PhD, professor of medicine at the Catholic University of Leuven, Belgium. "Results of the DEPICT-2 study were consistent with those of its twin study, DEPICT-1, which followed mostly European and American patients with type 1 diabetes. This new study had a greater global reach, with about a quarter of patients being from Asia. The benefits seen in both studies are important to people with T1D. Introduction of dapagliflozin as an adjunct therapy could be an interesting and exciting new treatment for T1D, almost 100 years after the discovery of life-saving insulin. However, adding dapagliflozin to the insulin regimen needs to be balanced against the increased risk of DKA, and this therapy should be coupled with intensive educational measures to cope with the small, but real risks."

The study has been accepted for publication and will be featured in its entirety in an upcoming issue of Diabetes Care, the ADA's peer-reviewed research journal dedicated to diabetes treatment and prevention. To speak with Dr. Mathieu, 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). 

78th Scientific Sessions
News Briefing: Adjunctive Therapies in Type 1 and Type 2 Diabetes, Sunday, June 24, 7:15 a.m.

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
Presentation Number: 213-OR

CHANTAL MATHIEU, PARESH DANDONA, PIETER GILLARD, PETER A. SENIOR, CHRISTOPH HASSLACHER, EIICHI ARAKI, MARCUS LIND, STEPHEN C. BAIN, SERGE JABBOUR, NIKI ARYA, FREDRIK A. THOREN, ANNA MARIA LANGKILDE, ON BEHALF OF THE DEPICT-2 INVESTIGATORS, Leuven, Belgium, Buffalo, NY, Edmonton, AB, Canada,
 Heidelberg, Germany, Kumamoto, Japan, Gothenburg, Sweden, Swansea, United Kingdom, Philadelphia, PA, Gaithersburg, MD, Mölndal, Sweden

The DEPICT-2 trial (NCT02460978) evaluated the efficacy and safety of dapagliflozin as add-on to adjustable insulin (INS) in patients (pts) with inadequately controlled T1D (A1c 7.5-10.5%) over 24 weeks. This phase 3 study randomized pts 1:1:1 to dapagliflozin5 mg (n=271), 10 mg (n=270) or placebo (PBO; n=272) plus INS. INS dose could be adjusted by the investigator according to self-monitored blood glucose readings, local guidance and individual circumstances. At Week 24, dapagliflozin5 and 10 mg significantly decreased A1c (0.37% and 0.42% reductions in the DAPA 5 mg and 10 mg groups respectively), total daily insulin dose (TDD), and body weight (Table). As measured by masked continuous glucose monitoring (CGM), mean interstitial glucose, mean amplitude of glucose excursion (MAGE) and mean percent of readings within target glycemic range (>70-≤180 mg/dL) vs. PBO were improved. There was an increase in pts who reduced their A1c by ≥0.5% without severe hypoglycemia (odds ratios [95% CI]: 2.71 [1.81, 4.06] and 3.07 [2.05, 4.60] for dapagliflozin 5 and 10 mg respectively). Hypoglycemic events, including severe hypoglycemia were balanced between treatment groups. There were more adjudicated definite diabetic ketoacidosis (DKA) events on dapagliflozin.
In conclusion, dapagliflozin vs. PBO as add-on to INS in pts with T1D was well tolerated, improved glycemic control and decreased variability without increasing hypoglycemia but with more DKA events.

Author Disclosures:  C. Mathieu: Research Support; Self; Novo Nordisk A/S. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Research Support; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Advisory Panel; Self; Sanofi. Research Support; Self; Merck Sharp & Dohme Corp. Speaker's Bureau; Self; Merck Sharp & Dohme Corp. Advisory Panel; Self; Merck Sharp & Dohme Corp. Research Support; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; Novartis AG. Speaker's Bureau; Self; Novartis AG. Advisory Panel; Self; Novartis AG, Bristol-Myers Squibb Company. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; AstraZeneca, Pfizer Inc., Janssen Pharmaceuticals, Inc., Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Hanmi Pharmaceutical. Research Support; Self; Roche Diagnostics Corporation. Advisory Panel; Self; Roche Diagnostics Corporation. Research Support; Self; Medtronic. Advisory Panel; Self; Medtronic, MannKind Corporation. Research Support; Self; Intrexon. Advisory Panel; Self; Intrexon, Dianax, UCB, Inc. Research Support; Self; Abbott. P. Dandona: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca. Research Support; Self; AstraZeneca. P. Gillard: None. P.A. Senior: Consultant; Self; Abbott, AstraZeneca. Research Support; Self; AstraZeneca, Prometic Life Sciences Inc., Novo Nordisk Inc., Sanofi. Consultant; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. Consultant; Self; Novo Nordisk Inc., Janssen Pharmaceuticals, Inc. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Speaker's Bureau; Self; AstraZeneca, Merck & Co., Inc., Abbott. Research Support; Self; Viacyte, Inc. C. Hasslacher: None. E. Araki: Speaker's Bureau; Self; Astellas Pharma US, Inc., MSD K.K., Kowa Pharmaceuticals America, Inc., Sanofi, Novo Nordisk Inc. Research Support; Self; Astellas Pharma US, Inc., MSD K.K., Ono Pharmaceutical Co., Ltd., Shionogi & Co., Ltd., Takeda Pharmaceuticals U.S.A., Inc., Daiichi Sankyo Company, Limited, Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Novo Nordisk Inc., Sanofi, Mitsubishi Tanabe Pharma Corporation, Sumitomo Dainippon Pharma Co., Ltd., Taisho Toyama Pharmaceutical Co. M. Lind: Consultant; Self; AstraZeneca. Research Support; Self; AstraZeneca. Consultant; Self; Novo Nordisk Inc. Advisory Panel; Self; Novo Nordisk Inc. Research Support; Self; Novo Nordisk Inc. Consultant; Self; Eli Lilly and Company. Research Support; Self; Dexcom, Inc. Consultant; Self; Eli Lilly and Company. Advisory Panel; Self; MSD K.K. Research Support; Self; Pfizer Inc. Consultant; Self; Medtronic. S.C. Bain: Research Support; Self; Novo Nordisk Inc., AstraZeneca. S. Jabbour: None. N. Arya: Employee; Self; AstraZeneca. F.A. Thoren: Employee; Self; AstraZeneca. A. Langkilde: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca.

Press Office in Orlando
June 22 - 26, 2018
407-685-4010

Contact:
Michelle Kirkwood
(703) 299-2053
mkirkwood@diabetes.org

SOURCE American Diabetes Association