Category: Diabetes/Prediabetes/Hypoglycemia

Monitor: 25

25 - Dapagliflozin induces an increase in plasma concentrations of ghrelin in patients with type 1 diabetes

Thursday, Apr 25
1:30 PM – 2:00 PM

Objective : In view of the fact that liraglutide suppresses appetite and food intake and acutely suppresses ghrelin concentrations in patients with type 1 diabetes, we have now investigated whether liraglutide and dapagliflozin exert an effect on plasma concentrations of ghrelin in the long term since we have used liraglutide in combination with dapagliflozin in  patients with type 1 diabetes.


Methods : Thirty type 1 diabetes patients were treated with insulin and liraglutide for 6 months randomized to 12 weeks of treatment with dapagliflozin 10 mg daily (n=20) or placebo (n=10).


Results : Liraglutide caused a fall in HbA1c by 0.34±0.11% (NS) compared to baseline while weight fell by 4.45±0.72kg (p<0.05 vs baseline). In the dapagliflozin group, HbA1c fell by an additional 0.66±0.08% from 7.8±0.21% (p<0.01 vs placebo) while body weight also fell by and additional 1.9±0.54kg (p<0.05 vs placebo).There was no significant change in fasting ghrelin concentrations after 6 months of liraglutide treatment. There was, however, a significant increase in ghrelin concentrations by 41±13% (from 412±48 to 587±53 pg/ml, p<0.05 compared to placebo) during the 12 weeks treatment with dapagliflozin. There was no significant change in carbohydrate intake following liraglutide while it increased by 21±12g/day (NS) following dapagliflozin


Discussion : Therefore, while liraglutide has an acute suppressive effect on plasma ghrelin concentrations, it has no sustained effect on fasting ghrelin concentrations in the long term. On the other hand, dapagliflozin has a marked stimulatory effect on plasma concentrations of ghrelin.


Conclusion : Whether this observation has any implications regarding food intake in patients on dapagliflozin needs further investigation.

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Husam A. Ghanim

ASSOCAITE PROFESSOR
State University of NY at Buffalo
Buffalo, New York

Dr. Ghanim is a research Associate Professor in the division of Endocrinology, Diabetes and Metabolism at University at Buffalo

Kelly Green

Research Associate
State University of NY at Buffalo

Research Associate at the University at Buffalo

Sanaa Abuaysheh

Research Associate
State University of NY at Buffalo

Research Associate at SUNY at Buffalo

Nitesh Kuhadiya

Endocrinology Program Director
Renown

Endocrinologist at Renown medical center, Director of Endocrinology

Manav Batra

Assistant Professor
University at Buffalo,SUNY
Williamsville, New York

Assistant Professor

Paresh Dandona

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.