Canagliflozin

To the Editor: In a recent CCJM review of canagliflozin,¹ this novel antihyperglycemic medication was noted to be associated with a dose-dependent increase in low-density lipoprotein (LDL) cholesterol, with an increase in LDL of 8.3 mg/dL (0.215 mmol/L) seen with the 300-mg/day dose of canagliflozin.

The Cholesterol Treatment Trialists’ (CTT) meta-analysis² showed a significant 21% proportional reduction in major vascular events per 1.0 mmol/L reduction in LDL cholesterol in people with diabetes treated with statins over an average of 4.3 years. If we assume that raising LDL cholesterol by 1.0 mmol/L has the opposite effect, then patients taking 300 mg per day of canagliflozin would be expected to suffer an increase in major vascular events of about 4.5% over 4.3 years. Put another way, for every 22 diabetic patients treated with canagliflozin over 4.3 years, one additional major vascular event would be expected on the basis of the associated increase in LDL cholesterol.

The CTT data also showed a significant 9% decrease in all-cause mortality for every 1.0 mmol/L decrease in LDL cholesterol. Again, assuming that raising LDL has the opposite effect of lowering it, then we should expect an additional death for each 52 diabetic patients treated with 300 mg/day of canagliflozin per day for 4.3 years.

The hypotensive side effect of canagliflozin might tend to mitigate some of the above adverse effects, as might its antihyperglycemic effect. Still, it would seem prudent to use this novel agent only as a second- or third-line choice, particularly in diabetic patients who have already suffered a major vascular event.

To the Editor: In a recent CCJM review of canagliflozin,¹ this novel antihyperglycemic medication was noted to be associated with a dose-dependent increase in low-density lipoprotein (LDL) cholesterol, with an increase in LDL of 8.3 mg/dL (0.215 mmol/L) seen with the 300-mg/day dose of canagliflozin.

The Cholesterol Treatment Trialists’ (CTT) meta-analysis² showed a significant 21% proportional reduction in major vascular events per 1.0 mmol/L reduction in LDL cholesterol in people with diabetes treated with statins over an average of 4.3 years. If we assume that raising LDL cholesterol by 1.0 mmol/L has the opposite effect, then patients taking 300 mg per day of canagliflozin would be expected to suffer an increase in major vascular events of about 4.5% over 4.3 years. Put another way, for every 22 diabetic patients treated with canagliflozin over 4.3 years, one additional major vascular event would be expected on the basis of the associated increase in LDL cholesterol.

The CTT data also showed a significant 9% decrease in all-cause mortality for every 1.0 mmol/L decrease in LDL cholesterol. Again, assuming that raising LDL has the opposite effect of lowering it, then we should expect an additional death for each 52 diabetic patients treated with 300 mg/day of canagliflozin per day for 4.3 years.

The hypotensive side effect of canagliflozin might tend to mitigate some of the above adverse effects, as might its antihyperglycemic effect. Still, it would seem prudent to use this novel agent only as a second- or third-line choice, particularly in diabetic patients who have already suffered a major vascular event.

To the Editor: In a recent CCJM review of canagliflozin,¹ this novel antihyperglycemic medication was noted to be associated with a dose-dependent increase in low-density lipoprotein (LDL) cholesterol, with an increase in LDL of 8.3 mg/dL (0.215 mmol/L) seen with the 300-mg/day dose of canagliflozin.

The Cholesterol Treatment Trialists’ (CTT) meta-analysis² showed a significant 21% proportional reduction in major vascular events per 1.0 mmol/L reduction in LDL cholesterol in people with diabetes treated with statins over an average of 4.3 years. If we assume that raising LDL cholesterol by 1.0 mmol/L has the opposite effect, then patients taking 300 mg per day of canagliflozin would be expected to suffer an increase in major vascular events of about 4.5% over 4.3 years. Put another way, for every 22 diabetic patients treated with canagliflozin over 4.3 years, one additional major vascular event would be expected on the basis of the associated increase in LDL cholesterol.

The CTT data also showed a significant 9% decrease in all-cause mortality for every 1.0 mmol/L decrease in LDL cholesterol. Again, assuming that raising LDL has the opposite effect of lowering it, then we should expect an additional death for each 52 diabetic patients treated with 300 mg/day of canagliflozin per day for 4.3 years.

The hypotensive side effect of canagliflozin might tend to mitigate some of the above adverse effects, as might its antihyperglycemic effect. Still, it would seem prudent to use this novel agent only as a second- or third-line choice, particularly in diabetic patients who have already suffered a major vascular event.