Journal ArticleDOI
Efficacy and safety of canagliflozin when used in conjunction with incretin-mimetic therapy in patients with type 2 diabetes
Greg Fulcher,David R. Matthews,Vlado Perkovic,Dick de Zeeuw,Kenneth W. Mahaffey,Chantal Mathieu,Vincent Woo,Carol Wysham,George Capuano,Mehul Desai,Wayne Shaw,Frank Vercruysse,Gary Meininger,Bruce Neal +13 more
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TLDR
Patients with type 2 diabetes enrolled in the CANagliflozin cardioVascular Assessment Study (CANVAS) who were on an incretin mimetic or glucagon‐like peptide‐1 (GLP‐1) receptor agonist are studied.Abstract:
Aims
To assess the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes enrolled in the CANagliflozin cardioVascular Assessment Study (CANVAS) who were on an incretin mimetic [dipeptidyl peptidase-4 (DPP-4) inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist].
Methods
CANVAS is a double-blind, placebo-controlled study that randomized participants to canagliflozin 100 or 300 mg or placebo added to routine therapy. The present post hoc analysis assessed the efficacy and safety of canagliflozin 100 and 300 mg compared with placebo in subsets of patients from CANVAS who were taking background DPP-4 inhibitors or GLP-1 receptor agonists with or without other antihyperglycaemic agents at week 18.
Results
Of the 4330 patients in CANVAS, 316 were taking DPP-4 inhibitors and 95 were taking GLP-1 receptor agonists. At 18 weeks, canagliflozin 100 and 300 mg provided larger placebo-subtracted reductions in glycated haemoglobin (HbA1c) in patients taking DPP-4 inhibitors [−0.56% (95% confidence interval [CI]: −0.77, −0.35), and −0.75% (95% CI: −0.95, −0.54), respectively] and GLP-1 receptor agonists [−1.00% (95% CI: −1.35, −0.65), and −1.06% (95% CI: −1.43, −0.69), respectively]. Body weight and blood pressure (BP) reductions were seen with canagliflozin versus placebo in both subsets. Higher incidences of genital mycotic infections and osmotic diuresis–related adverse events (AEs) were seen with canagliflozin compared with placebo. The incidence of hypoglycaemia was numerically higher with canagliflozin versus placebo; nearly all events occurred in patients on background insulin or insulin secretagogues.
Conclusions
In patients on background incretin mimetics, canagliflozin improved HbA1c, body weight and BP, with an increased incidence of AEs related to SGLT2 inhibition.read more
Citations
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Journal ArticleDOI
Exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy (DURATION-8): a 28 week, multicentre, double-blind, phase 3, randomised controlled trial
TL;DR: Exenatide plus dapagliflozin was significantly superior to either drug alone for all secondary efficacy endpoints, with greater reductions in fasting plasma and postprandial glucose, more patients with an HbA1c less than 7·0%.
Journal ArticleDOI
Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus
TL;DR: The pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM are assessed within the context of disease pathogenesis and natural history.
Journal ArticleDOI
Dulaglutide as add-on therapy to SGLT2 inhibitors in patients with inadequately controlled type 2 diabetes (AWARD-10): a 24-week, randomised, double-blind, placebo-controlled trial.
Bernhard Ludvik,Juan P. Frias,Francisco J. Tinahones,Julio Wainstein,Honghua Jiang,Kenneth E. Robertson,Luis-Emilio Garcia-Perez,D. Bradley Woodward,Zvonko Milicevic +8 more
TL;DR: The safety and efficacy of the addition of the once-weekly GLP-1 receptor agonist dulaglutide to the ongoing treatment regimen in patients whose diabetes is inadequately controlled with SGLT2 inhibitors, with or without metformin is assessed.
Journal ArticleDOI
SGLT2 inhibition in the diabetic kidney—from mechanisms to clinical outcome
Erik J.M. van Bommel,Marcel H. A. Muskiet,Lennart Tonneijck,Mark H. H. Kramer,Max Nieuwdorp,Daniël H. van Raalte +5 more
TL;DR: Interestingly, in the recently reported first cardiovascular safety trial with a sodium-glucose cotransporter type 2 inhibitor, empagliflozin improved both renal and cardiovascular outcomes in patients with type 2 diabetes and established cardiovascular disease.
Journal ArticleDOI
Emerging Role of SGLT-2 Inhibitors for the Treatment of Obesity
Maria J. Pereira,Jan W. Eriksson +1 more
TL;DR: The weight loss is clinically important, as most individuals with type 2 diabetes are overweight or obese, but also because there is an unmet need for safe, effective, and durable weight loss interventions in obese individuals without diabetes.
References
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Journal ArticleDOI
Management of Hyperglycemia in Type 2 Diabetes, 2015: A Patient-Centered Approach: Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes
Silvio E. Inzucchi,Richard M. Bergenstal,John B. Buse,Michaela Diamant,Ele Ferrannini,Michael A. Nauck,Anne L. Peters,Apostolos Tsapas,Richard C. Wender,David R. Matthews +9 more
TL;DR: This briefer article should be read as an addendum to the previous full account on the management of hyperglycemia, which described the need to individualize both treatment targets and treatment strategies with an emphasis on patient-centered care and shared decision making.
Management of Hyperglycemia in Type 2 Diabetes, 2015: A Patient- Centered Approach
Journal ArticleDOI
Intensive glucose control and macrovascular outcomes in type 2 diabetes
Fiona Turnbull,Carlos Abraira,Robert J. Anderson,Robert J. Anderson,Robert P. Byington,John Chalmers,William C. Duckworth,Gregory W. Evans,Hertzel C. Gerstein,Rury R. Holman,Thomas E. Moritz,Bruce Neal,Toshiharu Ninomiya,Anushka Patel,Sanjoy K. Paul,F. Travert,Mark Woodward,Mark Woodward +17 more
TL;DR: Targeting more-intensive glucose lowering modestly reduced major macrovascular events and increased major hypoglycaemia over 4.4 years in persons with type 2 diabetes, and suggests that glucose-lowering regimens should be tailored to the individual.
Journal ArticleDOI
Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial
William T. Cefalu,William T. Cefalu,Lawrence A. Leiter,Kun-Ho Yoon,Pablo Arias,Leo Niskanen,John Xie,Dainius Balis,William Canovatchel,Gary Meininger +9 more
TL;DR: Findings support the use of canagliflozin as a viable treatment option for patients who do not achieve sufficient glycaemic control with metformin therapy, and provide greater HbA1c reduction than does glimepiride, and is well tolerated in patients with type 2 diabetes receiving meetformin.