A Randomized Controlled Trial of Dapagliflozin Plus Once-Weekly Exenatide Versus Placebo in Individuals with Obesity and Without Diabetes: Metabolic Effects and Markers Associated with Bodyweight Loss.

Published on Jun 13, 2018in Diabetes Therapy3.179
· DOI :10.1007/S13300-018-0449-6
Maria J. Pereira17
Estimated H-index: 17
(Uppsala University),
Per Lundkvist5
Estimated H-index: 5
(Uppsala University)
+ 7 AuthorsJan W. Eriksson47
Estimated H-index: 47
(Uppsala University)
Sources
Abstract
Introduction The sodium-glucose cotransporter 2 inhibitor dapagliflozin and the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide reduce bodyweight via differing and complementary mechanisms. This post hoc analysis investigated the metabolic effects and baseline associations with bodyweight loss on coadministration of dapagliflozin and exenatide once weekly (QW) among adults with obesity and without diabetes.
📖 Papers frequently viewed together
37 Citations
21 Citations
4 Citations
References56
Newest
Obesity is a chronic disease with serious consequences and although lifestyle modification is considered first line treatment, it is often ineffective, especially in the long term. Relatively few people with obesity will undergo the most effective currently available treatment of bariatric surgery. Pharmacotherapy can bridge the gap between lifestyle modification and surgery, but many monotherapies have only modest efficacy or require high doses with unacceptable side effects. As with many other...
19 CitationsSource
#1Per Lundkvist (Uppsala University)H-Index: 5
#2Maria J. Pereira (Uppsala University)H-Index: 17
Last. Jan W. Eriksson (Uppsala University)H-Index: 47
view all 6 authors...
Aims Dapagliflozin and exenatide reduce body weight by differing mechanisms. Dual therapy with these agents reduces body weight, adipose tissue volume, glycaemia and systolic blood pressure (SBP) over 24 weeks. Here, we examined these effects over 1 year in obese adults without diabetes. Materials and methods Obese adults without diabetes (N = 50; aged 18-70 years; body mass index, 30-45 kg/m2) were initially randomized to double-blind oral dapagliflozin 10 mg once daily plus subcutaneous long-a...
29 CitationsSource
#1Robert S. Busch (Albany Medical College)H-Index: 16
#2Michael P. Kane (Albany College of Pharmacy and Health Sciences)H-Index: 16
ABSTRACTAmong persons with type 2 diabetes (t2d), the development of glucose intolerance involves dysfunction in several organs and tissues, including the muscle, liver, pancreas, kidney, gastrointestinal tract, adipose tissue, and brain. individuals with t2d typically have a number of comorbidities, including hypertension, hyperlipidemia, and being overweight or obese, and are, consequently, at high cardiovascular risk. guidelines recommend a comprehensive care strategy that includes treatment ...
26 CitationsSource
#1Karel A. Erion (BU: Boston University)H-Index: 4
#2Barbara E. Corkey (BU: Boston University)H-Index: 84
Purpose of Review This perspective is motivated by the need to question dogma that does not work: that the problem is insulin resistance (IR). We highlight the need to investigate potential environmental obesogens and toxins.
64 CitationsSource
#1Priscilla Hollander (Baylor University Medical Center)H-Index: 28
#2Harold E. BaysH-Index: 70
Last. Ngozi Erondu (Janssen Pharmaceutica)H-Index: 7
view all 7 authors...
OBJECTIVE To assess the efficacy and safety of coadministration of canagliflozin (CANA) and phentermine (PHEN) compared with placebo (PBO) and CANA or PHEN monotherapies in individuals who were overweight and obese without type 2 diabetes. RESEARCH DESIGN AND METHODS This 26-week, phase 2a, randomized, double-blind, PBO-controlled, multicenter, parallel-group study enrolled individuals who were obese or overweight without type 2 diabetes ( N = 335, aged 18–65 years, BMI ≥30 to 2 or BMI ≥27 to 2 ...
44 CitationsSource
#1Stefania Camastra (UniPi: University of Pisa)H-Index: 37
#2Brenno Astiarraga (UniPi: University of Pisa)H-Index: 18
Last. Ele FerranniniH-Index: 110
view all 8 authors...
Aims To investigate the effect of exenatide on glucose disposal, insulin secretion, s-cell function, lipolysis, and hormone concentrations in non-diabetic, morbidly obese subjects under physiological conditions. Materials and methods Patients were assigned to exenatide 10 µg twice daily (EXE, n = 15) or control (CT, n = 15) for 3 months. Patients received a meal test/tracer study (MTT) to measure endogenous glucose production (EGP), rate of oral glucose appearance (RaO), insulin secretion rate (...
9 CitationsSource
#1Per Lundkvist (Uppsala University)H-Index: 5
#2C. David Sjöström (AstraZeneca)H-Index: 16
Last. Jan W. Eriksson (Uppsala University)H-Index: 47
view all 6 authors...
Aims: To explore the effects of dual therapy with dapagliflozin and exenatide on body weight, body composition, glycaemic variables and systolic blood pressure (SBP) in obese adults without diabete ...
44 CitationsSource
#1Amalia Gastaldelli (University of Texas Health Science Center at San Antonio)H-Index: 85
#2Melania GagginiH-Index: 18
Last. Patricia IozzoH-Index: 46
view all 11 authors...
Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1-RAs) act on multiple tissues, in addition to the pancreas. Recent studies suggest that GLP-1-RAs act on liver and adipose tissue to reduce insulin resistance (IR). Thus, we evaluated the acute effects of exenatide (EX) on hepatic (Hep-IR) and adipose (Adipo-IR) insulin resistance and glucose uptake. Fifteen male subjects (age = 56 ± 8 years; body mass index = 29 ± 1 kg/m2; A1c = 5.7 ± 0.1%) were studied on two occasions, with a double-blin...
53 CitationsSource
#1Juan P. FriasH-Index: 26
#2Cristian Guja (UMFCD: Carol Davila University of Medicine and Pharmacy)H-Index: 23
Last. Serge Jabbour (Thomas Jefferson University)H-Index: 25
view all 7 authors...
Summary Background Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce glycaemia and weight, and improve cardiovascular risk factors via different mechanisms. We aimed to compare the efficacy and safety of co-initiation of the GLP-1 receptor agonist exenatide and the SGLT2 inhibitor dapagliflozin with exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled by metformin. Methods DURATION-8 was a 28 week,...
224 CitationsSource
#1David Polidori (Janssen Pharmaceutica)H-Index: 28
#2Arjun Sanghvi (NIH: National Institutes of Health)H-Index: 5
Last. Kevin D. Hall (NIH: National Institutes of Health)H-Index: 49
view all 4 authors...
Objective To quantify the feedback control of energy intake in response to long-term covert manipulation of energy balance in free-living humans. Methods A validated mathematical method was used to calculate energy intake changes during a 52-week placebo-controlled trial in 153 patients treated with canagliflozin, a sodium glucose co-transporter inhibitor that increases urinary glucose excretion, thereby resulting in weight loss without patients being directly aware of the energy deficit. The re...
96 CitationsSource
Cited By5
Newest
#1Prabhsimran Kaur (Central University of Punjab)H-Index: 1
#2Bidwan Sekhar Behera (Central University of Punjab)H-Index: 1
Last. Anjana Munshi (Central University of Punjab)H-Index: 24
view all 4 authors...
Diabetes, characterized by high glucose levels, has been listed to be one of the world's major causes of death. Around 1.6 million deaths are attributed to this disease each year. Persistent hyperglycemic conditions in diabetic patients affect various organs of the body leading to diabetic complications and worsen the disease condition. Current treatment strategies for diabetes include biguanides, sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, insulin and its analogs, DPP-4(dip...
Source
CONTEXT Glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors reduce weight and improve insulin sensitivity via different mechanisms. OBJECTIVE The efficacy of once-weekly exenatide (EQW) and dapagliflozin (DAPA) alone and co-administered (EQW/DAPA), DAPA/extended release metformin (DAPA/MET), and phentermine topiramate extended release (PHEN/TPM) on metabolic parameters, body composition, and sex hormones were examined in obese women with PCOS. RESEARCH DESIGN...
Source
Type 2 diabetes mellitus (T2D) is a chronic metabolic disease resulting from insulin resistance and progressively reduced insulin secretion, which leads to impaired glucose utilization, dyslipidemia and hyperinsulinemia and progressive pancreatic beta cell dysfunction. The incidence of type 2 diabetes mellitus is increasing worldwide and nowadays T2D already became a global epidemic. The well-known interindividual variability of T2D drug actions such as biguanides, sulfonylureas/meglitinides, DP...
7 CitationsSource
#1Maria J. Pereira (Uppsala University)H-Index: 17
#2Jan W. Eriksson (Uppsala University)H-Index: 47
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are glucose-lowering drugs that reduce plasma glucose levels by inhibiting glucose and sodium reabsorption in the kidneys, thus resulting in glucosuria. Their effects consequently include reductions in HbA1c, blood glucose levels, and blood pressure, but also reductions in body weight and adiposity. The ability to reduce body weight is consistently observed in individuals taking SGLT2 inhibitors, but this weight loss is moderate due to counter-r...
57 CitationsSource
Last. Biyue Wei
view all 3 authors...
Obesity has become a major topic of medical research in the world. In addition to diet control, exercising and behavioral therapy, many scholars now believe that drug therapy should be added to the routine treatment of obesity. It is confirmed that weight-loss drugs can help improve the health of obese patients, and patients who fail to intervene in lifestyle alone can benefit from drug treatment. Glucagon-like peptide-1 (GLP-1) is currently used in clinical blood glucose control drugs, but it h...
Source