The SGLPT2 inhibitors are the newest class of drugs used to treat people with diabetes.
They work by inhibiting reabsorption of sugar from the kidneys by the SGLPT2 transporters.
Since these transporters account for 90% of sugar reabsorption, their blockage results in significant loss of sugar in the urine.
This effect is independent of insulin.
Clinically, this results in lower sugar levels in the blood, both before and after meals.
The average HA1c reduction is 0.
7-1.
2% in studies ranging from 4-90 weeks.
Because calories are being lost as increased amounts of sugar are excreted in the urine (50 grams of glucose in the urine is equivalent to 200 calories), the drugs are also associated with weight loss.
Weight loss averages 5 pounds at 12 weeks.
In 12 month trials, reported weight loss ranges from 6-10 pounds.
Small, but clinically significant reductions in blood pressure are also seen with the SGLPT2 inhibitors, presumably due to both fluid loss and weight loss.
Uric acid levels may also decline.
Slight increases in LDL-cholesterol and HDL-cholesterol levels have been reported.
Studies are underway to determine their clinical significance.
The most commonly used SGLPT2 inhibitors are canagliflozin (Invokana) and dapagliflozin (Farziga).
Clinical efficacy and side effects are similar.
Both are once daily oral formulations.
The most common side effects are genital yeast infections (10% of women and 4% of men), presumably due to increased concentration of sugar in the urine.
Most of the genital infections in men occur in men who aren't circumcised.
Increased risk has not been reported in all trials.
Some people note increased urination.
Since insulin secretion isn't increased, and reabsorption is only inhibited when blood sugar levels are 90 mg/dl or more, hypoglycemia (low blood sugar) is rare when the SGLPT2 inhibitors are used alone.
Symptoms of volume depletion may occur (dizzy with standing).
This is seen most often in people 65 years or older, people who are dehydrated or being treated with fluid pills (diuretics), and/or people with underlying kidney dysfunction.
High potassium levels have been reported, most often in people taking blood pressure medications that block the renin-angiotensin system.
The efficacy of SGLPT2 inhibitors is greatest in people with healthy kidneys.
If your kidneys aren't filtering normally, enough sugar won't be filtered to allow the drugs to have a significant impact on reabsorption.
The drugs are not toxic to the kidneys.
SGLPT2 inhibitors should not be used in people with significantly reduced kidney function (i.
e.
those with GFR's < 45-60 ml/min).
Specific recommendations include avoid canagliflozin with a GFR <45 ml/min, at dapagliflozin at <60 ml.
min.
Long-term efficacy and safety for the SGLPT2's are unknown at this time.
As with all medications, discuss the pros and cons of treatment with your physician before beginning therapy.
They work by inhibiting reabsorption of sugar from the kidneys by the SGLPT2 transporters.
Since these transporters account for 90% of sugar reabsorption, their blockage results in significant loss of sugar in the urine.
This effect is independent of insulin.
Clinically, this results in lower sugar levels in the blood, both before and after meals.
The average HA1c reduction is 0.
7-1.
2% in studies ranging from 4-90 weeks.
Because calories are being lost as increased amounts of sugar are excreted in the urine (50 grams of glucose in the urine is equivalent to 200 calories), the drugs are also associated with weight loss.
Weight loss averages 5 pounds at 12 weeks.
In 12 month trials, reported weight loss ranges from 6-10 pounds.
Small, but clinically significant reductions in blood pressure are also seen with the SGLPT2 inhibitors, presumably due to both fluid loss and weight loss.
Uric acid levels may also decline.
Slight increases in LDL-cholesterol and HDL-cholesterol levels have been reported.
Studies are underway to determine their clinical significance.
The most commonly used SGLPT2 inhibitors are canagliflozin (Invokana) and dapagliflozin (Farziga).
Clinical efficacy and side effects are similar.
Both are once daily oral formulations.
The most common side effects are genital yeast infections (10% of women and 4% of men), presumably due to increased concentration of sugar in the urine.
Most of the genital infections in men occur in men who aren't circumcised.
Increased risk has not been reported in all trials.
Some people note increased urination.
Since insulin secretion isn't increased, and reabsorption is only inhibited when blood sugar levels are 90 mg/dl or more, hypoglycemia (low blood sugar) is rare when the SGLPT2 inhibitors are used alone.
Symptoms of volume depletion may occur (dizzy with standing).
This is seen most often in people 65 years or older, people who are dehydrated or being treated with fluid pills (diuretics), and/or people with underlying kidney dysfunction.
High potassium levels have been reported, most often in people taking blood pressure medications that block the renin-angiotensin system.
The efficacy of SGLPT2 inhibitors is greatest in people with healthy kidneys.
If your kidneys aren't filtering normally, enough sugar won't be filtered to allow the drugs to have a significant impact on reabsorption.
The drugs are not toxic to the kidneys.
SGLPT2 inhibitors should not be used in people with significantly reduced kidney function (i.
e.
those with GFR's < 45-60 ml/min).
Specific recommendations include avoid canagliflozin with a GFR <45 ml/min, at dapagliflozin at <60 ml.
min.
Long-term efficacy and safety for the SGLPT2's are unknown at this time.
As with all medications, discuss the pros and cons of treatment with your physician before beginning therapy.