Effectiveness and Tolerability of the Intensification of Canagliflozin Dose from 100 mg to 300 mg Daily in Patients with Type 2 Diabetes in Real Life: The INTENSIFY Study

Abstract

Aim: This study aimed to evaluate the effectiveness and tolerability of intensifying the dose of canagliflozin from 100 mg/day (CANA100) to 300 mg/day (CANA300) in patients with type 2 diabetes (T2DM) and suboptimal metabolic control in a real-world setting. Methods: A multicenter observational study was conducted on adult patients with T2DM who initiated treatment with CANA100 and subsequently required intensification to CANA300. The primary outcome measures were changes in HbA1c and weight at 6 months after the switch and at the end of the follow-up period. Results: A total of 317 patients met the inclusion criteria (59.6% male, mean age 62.2 years, baseline HbA1c 7.55%, weight 88.6 kg, median duration of treatment with CANA100 9.9 months). Switching to CANA300 resulted in a significant reduction in HbA1c (6 months: −0.33%; last visit: −0.47%, both p < 0.0001) and weight (6 months: −1.8 kg; last visit: −2.9 kg, both p < 0.0001) over a median follow-up period of 20.8 months. The proportion of patients that achieved HbA1c < 7% increased from 26.7% with CANA100 to 51.6% with CANA300 (p < 0.0001). Among individuals with poor baseline glycemic control (HbA1c > 8%, mean 9.0%), HbA1c was significantly reduced by −1.24% (p < 0.0001). Furthermore, significant improvements were observed in fasting plasma glucose (FPG), blood pressure (BP), liver enzymes, and albuminuria. No unexpected adverse events were reported. Conclusions: Intensifying the treatment to CANA300 in a real-world setting resulted in further significant and clinically relevant reductions in FPG, HbA1c, weight, and BP in patients with T2DM. The switch was particularly effective in patients with higher baseline HbA1c levels.

SGLT2 Inhibitors – The New Standard of Care for Cardiovascular, Renal and Metabolic Protection in Type 2 Diabetes: A Narrative Review

“…The CVD-REAL 3 study provided further real-world evidence concerning the impact of SGLT2is in decelerating kidney function decline ( p < 0.0001) and the risk of major kidney events ( p < 0.0001), compared with other oral glucose-lowering therapies [ 51 ]. Moreover, recent real-world data showed that increasing canagliflozin dosage to the highest approved level in individuals with T2DM and less-than-optimal metabolic results led to notable enhancements in key factors including fasting plasma glucose, HbA1c, body weight and blood pressure, complementing the existing cardiorenal protection offered by lower-dose therapy [ 52 ]. Real-world studies reaffirmed well-established data from large randomised controlled cardiovascular outcomes trials (CVOTs; EMPA-REG Outcome, CANVAS, DECLARE-TIMI 58), which have provided an ever-expanding body of evidence regarding SGLT2i-related reductions in CV events, including composite endpoints that encompass major adverse cardiovascular events (MACE), heart failure (HF) and CV death, HHF and worsening HF events [ 17 , 18 , 53 ].…”

“…The EMPA-KIDNEY (empagliflozin) and DAPA-CKD (dapagliflozin) trials showed similar results in individuals with CKD, whether or not they had T2DM [ 21 , 28 , 31 ]. SGLT2i use has also been typically associated with the lowering of other CV risk factors, such as blood pressure, and recipients often experience weight loss [ 2 , 12 , 17 , 18 , 34 , 35 , 49 , 52 , 53 , 57 – 60 ]. Organ protection remains the cornerstone objective for long-term management of T2DM and the wider implementation of SGLT2is early in the therapeutic pathway would support better outcomes through the lowering of both macrovascular risk and complication severity [ 1 – 4 , 12 , 17 – 23 , 28 , 31 , 35 , 52 , 53 , 56 , 61 ].…”