How effective and safe are SGLT2 inhibitors combined with insulin for type 1 diabetes?

This study investigated the effectiveness and safety of adding SGLT2 inhibitors to insulin in type 1 diabetes (T1D). The authors concluded that add-on SGLT-2 inhibitor therapy may be helpful for T1D, but should be carefully considered due to potential side effects.

The goal of T1D management is to reach and maintain normal glucose levels. Typically, this is achieved through insulin injection. However, insulin therapy is associated with hypoglycemia (low blood sugar) and weight gain, making long-term management difficult.

Sodium-glucose co-transporter 2 inhibitors (SGLT2 inhibitors) are a type of treatment that help the kidneys remove glucose from the body through the urine. SGLT-2 inhibitors have been shown to improve blood sugar control and body weight in type 2 diabetes. It is not clear whether they are also effective in T1D.

This study analyzed the results of 14 other studies comparing SGLT-2 inhibitor therapy to placebo (substance with no active effect) in patients with T1D. There were 4,591 patients included in the studies. Therapies included sotagliflozin, dapagliflozin (Farxiga), canagliflozin (Invokana), and empagliflozin (Jardiance). In each study, the follow-up period was at least 2 weeks or more.

SGLT-2 inhibitor therapy reduced HbA1c levels by 0.4%, and fasting blood sugar levels by 1.14 mmol/l. Bolus insulin (insulin taken at mealtimes) doses decreased by 3.6 units per day. Basal insulin (long-acting insulin) doses decreased by 4.2 units per day. Body weight decreased by 2.68 kg, and systolic blood pressure (blood pressure when the heart beats) lowered by 3.37 mmHg. These were all statistically significant.

There was no significant difference in the risk of hypoglycemia. SGLT-1 inhibitors were associated with 3.38-fold higher odds of ketoacidosis (a serious condition that occurs when the cells of the body do not get enough glucose for energy and the body begins to burn fat at a high rate). The odds of genital infections were 3.44-times higher.

The authors concluded that add-on SGLT-2 inhibitor therapy may be advantageous for type 1 diabetes, particularly overweight or obese patients. However, it should be carefully considered due to increased risks of ketoacidosis and genital infections.

Most of the studies analyzed here received industry funding. Further studies are needed to determine the benefits of SGLT-2 inhibitor therapy versus the risk of side effects.