High dose canagliflozin effective in achieving good blood sugar control in T2 Diabetes

Intensifying the dose of canagliflozin therapy from 100 mg/day (CANA100) to 300 mg/day (CANA300) has effectively and significantly reduced the fasting plasma glucose levels, blood pressure, HbA1c, and weight in patients with type 2 diabetes (T2DM). The switch was particularly effective in patients with higher baseline HbA1c levels.The study was published in the Journal of Clinical Medicine. 

Sodium-glucose cotransporter type 2 (SGLT-2) inhibitors are orally administered glucose-lowering drugs (GLDs) that enhance urinary glucose excretion (UGE), leading to an effective reduction in pre- and postprandial glycemia, HbA1c, body weight, and blood pressure (BP) in patients with type 2 diabetes. These also have significant cardio- and renoprotective effects. Canagliflozin 300 mg (CANA300), an SGLT-2 inhibitor has the unique feature of inhibiting the sodium-glucose cotransporter type 1 (SGLT-1) in the small intestine, leading to reduced postprandial blood glucose levels. Real-world evidence from some studies has shown that intensifying the dose of canagliflozin from 100 mg/day to 300 mg/day in patients with suboptimal metabolic control will achieve better glycemic control. Hence researchers conducted a retrospective multicenter study in Madrid, Spain to assess the effectiveness and tolerability of increasing the canagliflozin dose from 100 mg/day to 300 mg/day in patients with T2DM and suboptimal metabolic control. 

Adult patients with T2DM who initiated treatment with CANA100 and subsequently required intensification to CANA300, an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 and with a duration of 6 months from the intensification were enrolled in the study. The primary outcome measures were changes in HbA1c and weight at 6 months after the switch and the end of the follow-up period. 

Key findings: 

• About 317 patients met the inclusion criteria. Out of them there were 59.6% male, mean age 62.2 years, baseline HbA1c 7.55%, weight 88.6 kg, median duration of treatment with CANA100 was 9.9 months. 
• There was a significant reduction in HbA1c and weight after switching to CANA300 over a median follow-up period of 20.8 months. 
• There was an increase in the proportion of patients that achieved HbA1c < 7% 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).
• Significant improvements were also observed in other factors like the fasting plasma glucose (FPG), blood pressure (BP), liver enzymes, and albuminuria.
• No unexpected adverse events were reported. 

Thus, in a real-world setting, intensifying the treatment and switching to CANA300  resulted in further significant and clinically relevant reductions in FPG, HbA1c, weight, and BP in patients with T2DM. 

Further reading: 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.J. Clin. Med. 2023, 12(13), 4248.  https://doi.org/10.3390/jcm12134248