The 24-week results of the Phase 3 DEPICT-1 and -2 trials, which studied the effects of treatment with the sodium–glucose cotransporter-2 inhibitor dapagliflozin (DAPA) as adjunct to adjustable insulin in patients with type 1 diabetes (T1D), have been reported elsewhere. Here we present results of the analyses of standard deviation (SD) of glucose readings from pooled data from DEPICT-1 and -2 at Weeks 12 and 24 for DAPA vs placebo (PBO).
Methods : As the DEPICT studies were of similar design and patients had similar baseline characteristics, post-hoc analyses of pooled continuous glucose monitoring (CGM) data from the first 24 weeks can be readily performed. All patients had CGM for 2-week periods at baseline and prior to the Week 12 and 24 visits. The efficacy analyses set from these studies included 1591 patients (DAPA 5 mg: N=530; DAPA 10 mg: N=529; PBO: N=532). Data were analysed using mixed model repeated measures.
Treatment with DAPA 5 and 10 mg improved the SD of glucose from 67.16 (+/-12.288) mg/dL and 67.45 (+/-12.831) mg/dL at baseline to 59.89 (+/-13.357) mg/dL and 60.06 (+/-12.654) mg/dL, respectively at Week 12, and 61.15 (+/-14.308) mg/dL and 61.16 (+/-13.494) mg/dL, respectively at Week 24. For PBO, the SD of glucose was 66.33 (+/-12.737) mg/dL at baseline, 65.45 (+/-12.473) mg/dL at Week 12, and 66.12 (+/-13.112) mg/dL at Week 24. Difference in SD vs PBO was −6.01 (95% CI: −7.27, −4.76) mg/dL with DAPA 5 mg and −5.90 (−7.15, −4.65) mg/dL with DAPA 10 mg at Week 12, and −5.53 (−6.93, −4.12) mg/dL and −5.69 (−7.10, −4.28) mg/dL, respectively, at Week 24.
Previous analyses of pooled CGM data from the DEPICT studies have shown that DAPA 5 and 10 mg vs PBO improves time-in-range (TIR) by 9.07% and 10.67% (corresponding to 2.11 hrs and 2.48 hrs), respectively, without increasing time in the hypoglycemic range. International consensus on use of CGM recommends assessing variability in addition to TIR. Variability as assessed by mean amplitude of glucose excursion (MAGE) has previously been shown to be reduced with DAPA vs PBO. Here we also show improvements in SD.
Conclusion : Consistent with the improvements seen in TIR and MAGE, treatment with DAPA in patients with T1D improves the SD of interstitial glucose.
Yehuda Handelsman– Medical Director & Principal Investigator, Metabolic Institute of America, Tarzana, California, USA, Los Angeles, California
Paresh Dandona– Chief of the Division of Endocrinology, Metabolism and Diabetes, State University of New York at Buffalo, Williamsville, New York
Chantal Mathieu– Chair of Endocrinology at the University Hospital Gasthuisberg Leuven, KU Leuven, Leuven, Belgium
Marcus Lind– Senior lecturer/ Chief physician, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; Department of Medicine, NU-Hospital Group, Uddevalla, Sweden, Uddevalla, Sweden
Moshe Phillip– Director, Institute for Endocrinology and Diabetes National Center for Childhood Diabetes, Schneider Children’s Medical Center of Israel; Professor and Vice Dean for Research and Development, Sackler Faculty of Medicine Tel Aviv University, Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel; Sackler Faculty of Medicine Tel Aviv University, Petah Tikva, Israel
Markus Scheerer– Global Medical Affairs Lead, Medical Department, AstraZeneca GmbH, Wedel, Germany, Wedel, Germany
Niki Arya– Principal Statistician, AstraZeneca, MD, Maryland
Fredrik Thorén– Research Physician-Specialist in Internal Medicine and Endocrinology, AstraZeneca, Mölndal, Sweden
Anna-Maria Langkilde– Global Clinical Leader, AstraZeneca Gothenburg, Sweden, Mölndal, Sweden
Medical Director & Principal Investigator
Metabolic Institute of America, Tarzana, California, USA
Los Angeles, California
Yehuda Handelsman, MD, FACP, FNLA, FASPC, MACE is an endocrinologist in private practice, and Medical Director & Principal Investigator of the Metabolic Institute of America. He is a nationally and internationally recognized authority on Diabetes, Lipids, Obesity, hypertension and it's complications, and management and prevention of Cardiovascular disease. He has published over 120 peer reviewed original research & review papers, editorials, and book chapters. His Book ‘Clinical Management of Cardiovascular Risk in Diabetes and Obesity’ is published by Professional Communications, Inc. He chaired the consensuses on SGLT2i & DKA, Diabetes, Obesity & Cancer, Insulin Resistance Syndrome, lipodystrophy and Pre-Diabetes and holds/has held the following positions:
• A Master of the American College of Endocrinology
• Fellow of the American Society of Preventive Cardiology,
• Fellow of the American College of Physicians
• Fellow of the The National lipid Association
• Immediate Past President of the Pacific Lipid Association
• Member Board of Directors, American Association for Preventive Cardiology,
• Chair of the American Association of Clinical Endocrinologists (AACE) Lipid & CV Health Disease network
• Member of the AACE Diabetes & Obesity Disease networks.
• Chair & program director of the annual World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease and
• Chair & program director The Heart in Diabetes- initiative and Medical Congress
• Chair & Founder the International Lipid Forum
• Past president of the American College of Endocrinology
• Past president of the AACE
Chief of the Division of Endocrinology, Metabolism and Diabetes
State University of New York at Buffalo
Williamsville, New York
Dr. Dandona is a Distinguished Professor of Medicine and chief of the Division of Endocrinology, Diabetes and Metabolism, at the University at Buffalo, The State University of New York. He is also the founder and director of the Diabetes–Endocrinology Center of Western New York in Buffalo. Previously, he served as director of Diabetes and Metabolism at the Royal Free Hospital School of Medicine at the University of London, England, for 14 years. One of the world’s leading experts in the treatment of diabetes and vascular disease, Dr. Dandona is a Rhodes Scholar from India, trained at the University of Oxford and the University of London.
The Diabetes Endocrinology Center of Western New York probably has the finest standards of diabetic care anywhere: it is 21 years since the last chronic diabetic foot ulcer, gangrene or amputation was observed, while it is 16 years since the last patient had diabetic end stage renal failure. Dr Dandona received the Valor Award of the American Diabetes Association for his contributions to the standards of care in diabetes and the establishment of a network of diabetes care in Western New York.
He received the Pharmacia-Pfizer/Endocrine Society Award for the discovery of the anti-inflammatory effect of insulin. This discovery has been extended into potential cardio-protective and neuro-protective effects of insulin in acute myocardial infarction, stroke and Alzheimer’s disease. Trials are under way to translate these concepts into clinical practice. His work on obesity, oxidative stress and inflammation, and the pro-inflammatory effects of macronutrients (foods) is now recognized globally. His team is currently busy investigating potential anti-inflammatory foods. The third major discovery by his team is that of low testosterone concentrations in males with Type 2 Diabetes and obesity. His team has demonstrated that this is the most common cause of male hypogonadism and potentially infertility. He is currently leading pioneering trials on the benefits of testosterone replacement and other treatments in such patients. These studies show that hypogonadal patients are more insulin resistant and that testosterone treatment reverses this defect. His group also leads the world in adjunct treatments of type 1 diabetes.
Most recently, his group has taken global lead in the area of adjunct therapies in patients with type 1 diabetes. Thus, liraglutide and dapagliflozin, the two drugs licensed for use in type 2 diabetes, have both been shown to improve glycemic control in patients with type1 diabetes. As a result, Dapagliflozin is likely to be approved by the European Medicines Agency to approve the use of dapagliglozin in type 1 diabetes. He has recently been awarded with the largest grant ever from the Juvenile Diabetes research Foundation to investigate the effect of ‘triple therapy’ (insulin, semaglutide and dapagliflozin) in patients with type 1 diabetes. He has ben recognized internationally by the Fernando Medal of the Ceylon (Sri Lanka) College of Physicians; the Banting Award of the Endocrine Society of India; the Viswanathan Medal of the Research Society for Diabetes in India; the Ricardo Fernando Medal of the Diabetes Society of Philippines; and as Global Eminent Scholar of Kyung Hee University of South Korea.
Dr. Dandona has published more than 590 publications in peer-reviewed medical journals, and has presented keynote lectures on diabetes and insulin resistance at many national and international conferences. He is the founder editor of Metabolic Syndrome and Related Disorders, and is or has been on the editorial boards of the Journal of Clinical Endocrinology and Metabolism, Diabetes Care, Current Diabetes Reviews and Journal of Diabetes.
Chair of Endocrinology at the University Hospital Gasthuisberg Leuven
Chantal Mathieu is Professor of Medicine at the Katholieke Universiteit Leuven, Belgium. She is Chair of Endocrinology at the University Hospital Gasthuisberg Leuven. Prof. Mathieu received her medical degree and PhD at the University of Leuven, where she subsequently completed training in internal medicine and endocrinology. Prof. Mathieu’s clinical areas of interest include the organization of diabetes care, and she is involved in several clinical trials in type 1 and type 2 diabetes. Her basic research is focused on the prevention of type 1 diabetes, effects of vitamin D on the immune system and diabetes, and functioning of the insulin-producing beta cell. Prof. Mathieu has authored or co-authored more than 330 peer-reviewed publications in international journals. She is a past associate editor and advisory board member of Diabetologia. In 2013, Prof. Mathieu received the prestigious InBev-Baillet Latour Prize for Clinical Research for her pioneering research on the pathogenesis of type 1 diabetes. She presently coordinates the INNODIA project on prevention and intervention in type 1 diabetes in Europe.
Senior lecturer/ Chief physician
Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; Department of Medicine, NU-Hospital Group, Uddevalla, Sweden
Marcus Lind presented his thesis in 2009 at the University of Gothenburg with a focus on evaluating the effects of modern insulin analogues and HbA1c as a risk factor for diabetic complications. During his post-doc period he performed work at the Mid-America Heart Institute, Missouri University, US. Besides his research he has worked as a chief clinical physician of Diabetology at the NU (NÄL and Uddevalla)-Hospital Group. He became Associate Professor of Diabetology in 2014 at the University of Gothenburg and has performed essential research both in the epidemiologic field and in clinical randomized trials which have been presented in New England Journal of Medicine, Lancet, The Journal of the American Medical Association, and British Medical Journal. He has been in charge of over 40 studies.
Prize for good scientific methodology and presentation at the "National meeting for physicians in Sweden in 2006"
Prize as the “Diabetologist of the year” in Sweden in 2009 for research of metabolic memory and diabetic complications in the DCCT study
Prize for best diabetic publication in Sweden in 2011 regarding Heart Failure in Persons with Type 1 Diabetes. (Lind. M., Lancet, June, 2011)
Director, Institute for Endocrinology and Diabetes National Center for Childhood Diabetes, Schneider Children’s Medical Center of Israel; Professor and Vice Dean for Research and Development, Sackler Faculty of Medicine Tel Aviv University
Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel; Sackler Faculty of Medicine Tel Aviv University
Petah Tikva, Israel
A leading endocrinologist and the director of Israel’s Institute for Endocrinology and Diabetes at Schneider Children's Medical Center, with over 20 years of clinical experience treating type 1 diabetes patients using insulin pumps and continuous glucose sensors.
Global Medical Affairs Lead
Medical Department, AstraZeneca GmbH, Wedel, Germany
Dr. Markus Florian Scheerer, PhD, has a strong scientific background in Diabetes and Oncology and his interests include supporting LCM processes, disease education, and medical launches of new molecular entities, combinations or new indications of products for maximizing global patient benefit, including strategic in-licensing opportunities. He currently works as Global Medical Affairs Lead for AstraZeneca in Wedel.
Niki Arya has been working as a statistician in the Cardiovascular and Metabolic Diseases area at AstraZeneca since 2015. She has a BS in Chemistry from UNC-Chapel Hill, an MS in Epidemiology from the University of Virginia, and an MS in Biostatistics from UNC-Chapel Hill. Prior to her position at AstraZeneca, she was a statistician at GlaxoSmithKline for 11 years, where she worked in the Oncology, Metabolic Diseases, HIV, and Neurosciences therapeutic areas.
Research Physician-Specialist in Internal Medicine and Endocrinology
I have a university degree in Biology (BSc Adv Major) after which I obtained a Medical Degree (MD), both at Dalhousie University in Halifax, NS, Canada. I have conducted research in mitocondrial genetics and wheelchair stability and completed a residency in Internal Medicine followed by Endocrinology (Diabetology). I was active at the Diabetes and the Obesity outpatient clinics at the Sahlgrenska Hospital and worked part-time at the CRO, NMCT (Nordic Management of Clinical Trials). I have also done language reviews and translations of medical papers for publication either for European or US journals in particular for PhD theses. I have worked at AstraZeneca,since 2011, in Mölndal, Sweden, initially in Patient Safety, but since 2013 as a Research Physician in late stage diabetes studies as well as with Market Access.
Global Clinical Leader
AstraZeneca Gothenburg, Sweden
Anna Maria Langkilde, MD PhD, is Global Clinical and Scientific Lead for Oral Diabetes at AstraZeneca, Biopharmaceutical R&D. She earned her Medical Degree from Gothenburg University and Sahlgrenska University Hospital in Gothenburg, Sweden and has a clinical and scientific background in the field of Internal Medicine, with a focus on diabetes, obesity and metabolism.