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Canagliflozin and Its Effects on Weight Loss and BP

Treatment with canagliflozin, an SGLT-2 inhibitor, was associated with reductions in body weight, HbA1c and systolic blood pressure….

Pooled data from four placebo-controlled Phase 3 studies (N = 2,250) in patients with type 2 diabetes were used in the analyses. In each study, patients were treated with placebo, canagliflozin 100 mg or canagliflozin 300 mg, once daily for 26 weeks. Changes from baseline in body weight, HbA1c and SBP were measured at week 26, and the contribution of weight loss to the lowering of HbA1c and SBP was obtained using ANCOVA. Each study had a primary assessment at 26 weeks and evaluated canagliflozin 100 and 300 mg vs placebo as monotherapy, add-on to metformin, add-on to metformin plus sulfonylurea, or add-on to metformin plus pioglitazone. Eligible patients were aged 18–80 years, and generally had HbA1c ≥7.0% and ≤10.5% and estimated glomerular filtration rate ≥55 ml/min. During the study, changes in body weight, HbA1c, and systolic blood pressure were assessed several times between baseline and week 26 of the study.

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Patients had mild to moderate hyperglycemia at baseline (mean HbA1c, 8.0%). Of the patients included in these analyses, ≥30% of patients were overweight (BMI ≥25 and <30 kg/m2) and ≥50% of patients in each study were obese (BMI ≥30 kg/m2). Changes in body weight, HbA1c, and systolic blood pressure were seen using either 100mg or 300mg of canagliflozin compared to the placebo group. Most patients who were treated saw a reduction in HbA1c. More patients treated with canagliflozin 100 and 300 mg vs placebo had ≥ 5% weight loss (25%, 33% and 6%, respectively) and≥10% weight loss (3%, 3% and 1%,). Also, a reduction in systolic blood pressure was 0.062mmHg.

Most antihyperglycemic agents are found to cause weight gain in patients with type 2 diabetes. As reported, canagliflozin treatment was associated with reductions in body weight, HbA1c and systolic blood pressure.

Practice Pearls:

  • Most antihyperglycemic therapies are considered either weight loss or neutral (i.e., biguanides, bile acid sequestrants, bromocriptine, dipeptyl-peptidase inhibitors, α-glucosidase inhibitors).
  • Prior to the introduction of SGLT2 inhibitors, glucagon-like peptide-1 receptor (GLP-1) agonists were the only class consistently associated with body-weight reduction in patients with type 2 diabetes.

Cefaula W, Stenloaf K, Leiter L et al. Effects of canagliflozin on body weight and relationship to HbA1c and blood pressure changes in patients with type 2 diabetes. Diabetologia June 2015. 58:3547. DOI: 10.1007/s00125-015-3547-2.