Efficacy and safety of canagliflozin as add‐on therapy to a glucagon‐like peptide‐1 receptor agonist in Japanese patients with type 2 diabetes mellitus: A 52‐week, open‐label, phase IV study

Abstract

Sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors and glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) are antihyperglycaemic agents with weight‐lowering effects. The efficacy and safety of the SGLT2 inhibitor canagliflozin as add‐on therapy in Japanese patients with type 2 diabetes mellitus (T2DM) and inadequate glycaemic control with a GLP‐1RA (≥12 weeks) were evaluated in this phase IV study. Patients received canagliflozin 100 mg once daily for 52 weeks. Efficacy endpoints included change in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), body weight, systolic blood pressure (SBP) and HDL cholesterol from baseline to week 52. Safety endpoints included adverse events (AEs), hypoglycaemia and laboratory tests. Of the 71 patients treated with canagliflozin, 63 completed the study. At 52 weeks, HbA1c was significantly reduced from baseline (−0.70%; paired t test, P < .001). Significant changes were also observed in FPG (−34.7 mg/dL), body weight (−4.46%), SBP (−7.90 mm Hg), and HDL cholesterol (7.60%; all P < .001). The incidence of AEs, adverse drug reactions and hypoglycaemia was 71.8%, 32.4% and 9.9%, respectively. All hypoglycaemic events were mild. These findings suggest that the long‐term combination of canagliflozin with a GLP‐1RA is effective and well tolerated in Japanese patients with T2DM.

Combination therapy with SGLT-2 inhibitors and GLP-1 receptor agonists as complementary agents that address multi-organ defects in type 2 diabetes

“…In the AWARD-10 study, addition of dulaglutide 1.5 mg to SGLT-2i therapy was associated with significant reductions compared with placebo in body weight (-3.1 vs -2.1 kg; p = 0.028) and systolic BP (-4.5 vs -1.4 mm Hg; p = 0.021) [64]. Other studies in which SGLT-2i therapy was added to GLP-1RA treatment showed similar results, with significant improvements in BP and body weight (Table 1) [62,63,67].…”

“…In the Assessment of Weekly Administration of LY2189265 (dulaglutide) in Diabetes-10 (AWARD-10) study, addition of the GLP-1RA dulaglutide to stable SGLT-2i therapy was associated with significantly greater reductions in A1c from baseline to 24 weeks (-1.21% and -1.34% for the 0.75-mg and 1.5-mg doses, respectively) compared with placebo (-0.54%; p < 0.0001 for both doses) [64]. In real-world observational studies, in which an SGLT-2i was added to GLP-1RA background therapy (with or without other glucose-lowering therapies), the mean incremental change in A1c with the combination ranged from -0.39% to −1.5% [62,63,[65][66][67].…”

“…[61][62][63][64]. In the Exenatide Once Weekly Plus Dapagliflozin Once Daily Versus Exenatide or Dapagliflozin Alone in Patients With Type 2 Diabetes Inadequately Controlled With Metformin Monotherapy…”

Revisão sobre a eficácia e segurança no uso de inibidores de co-transportadores de sódio-glicose-2 na fisiopatologia da diabetes mellitus tipo II

“…Os desfechos mostraram reduções significativas na HbA1c em todos os momentos, incluindo redução de peso e de pressão arterial. Contudo, foram identificados eventos adversos como candidíase vulvovaginal e hipoglicemia em 10% dos pacientes (HARASHIMA et al, 2018).…”

Efficacy of Canagliflozin as an Add-on to Triple Drug Treatment With Glimepiride, Metformin and Teneligliptin

“…8 Several national and international studies have demonstrated the long-term effectiveness of canagliflozin as an add-on to dipeptidyl peptidase-4 inhibitors and glucagonlike peptide-1 receptor agonists. 10,11 Canagliflozin is commonly used at daily doses of 100 and 300 mg. 12 The drug has demonstrated remarkable reduction in blood pressure, body weight and has lower risk of hypoglycaemia. 13 Kadowaki et al (2018) have reported the long-term safety and efficacy of canagliflozin, as an add-on to teneligliptin, in Japanese T2DM patients with inadequate glycemic control.…”