A Scoping Review Evaluating the Effect of SGLT-2 Inhibitors on Insulin Dose Requirements in Insulin-Dependent Patients With Type 2 Diabetes

A Scoping Review Evaluating the Effect of SGLT-2 Inhibitors on Insulin Dose Requirements in Insulin-Dependent Patients With Type 2 Diabetes
Anna Lange, PharmD, Goodrich Pharmacy

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2-I) are commonly used as an adjunct medication for patients with type 2 diabetes. Currently, there are four SGLT2-Is on the market in the US: canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin. These medications have been proven to lower blood glucose levels, reduce cardiovascular risk, reduce progression of chronic kidney disease, and improve outcomes in heart failure with both preserved and reduced ejection fraction. To date, there have not been any large randomized controlled trials assessing SGLT2-Is and total daily insulin (TDI) requirements, though there are various smaller studies that have looked at these endpoints.

Objective: The objective of this scoping review was to assess evidence on the effect of SGLT2-Is on TDI requirements in patients with type 2 diabetes who are insulin dependent.

Study Design: This scoping review examined studies from January 1, 2005 to April 12, 2021 assessing insulin dose requirements with concurrent use of an SGLT2-I. There were 16 studies included in the scoping review based on inclusion criteria of patients with type 2 diabetes, concurrent use of insulin and SGLT2-I, a study design of 12 weeks or longer, and a description of changes in insulin dose. Three studies were prospective open-label trials, one trial used a retrospective design, and the other 12 studies were prospective, randomized, double-blind, placebo-controlled trials. All studies evaluated insulin doses at baseline and follow-up. Ten studies included dapagliflozin as the SGLT2-I.

ResultsThree studies found a statistically significant decrease in mean insulin dose from baseline to follow-up, with decreases of 2.8 units at 16 weeks, 6.6 units at 24 weeks, and 18.4 units at 12 weeks. In Pujante et al, there was a statistically significant decrease in TDI for patients with an A1c <7.5%, but no statistically significant decrease for the patients with an A1c of >7.5%. In the 13 remaining studies, baseline TDI ranged from 27 units to 93 units. The mean insulin dose change from baseline to follow-up in the SGLT2-I groups ranged from an increase of 4.7 units to a decrease of 2.33 units. Changes in total daily rapid insulin versus total daily basal insulin individually were not found to be significant. Two studies found a reduction in TDI of >10% that was significant.

Of 12 studies, eight reported a significant decrease in TDI requirements. The difference in TDI requirements between insulin with placebo versus insulin with SGLT2-I ranged from -0.72 units to -19.2 units. Across all studies, hypoglycemic events varied, but adverse events were minimal.

Conclusion: SGLT2-Is, in addition to insulin in uncontrolled insulin-dependent type 2 diabetes patients, significantly reduced TDI requirements in the majority of studies and across all study designs in this review. Larger randomized controlled trials are needed to assess the effect on insulin dosing, including assessing for differences in the reduction of basal insulin versus bolus insulin when adding an SGLT2-I.

Key Point: SGLT2-Is, in addition to insulin therapy in type 2 diabetes patients above their A1c goal, may reduce TDI requirements in addition to the known cardiovascular and renal benefits.

Reference:

  1. Moulton MK, Johnson BR, Lavender DL, et al. A scoping review evaluating the effect of SGLT-2 inhibitors on insulin dose requirements in insulin-dependent patients with type 2 diabetes. Ann Pharmacother. Published online Jan 18, 2022. doi: 10.1177/10600280211071089.