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Addition of SGLT2 Inhibitor when Glycemic Control Cannot be Attained with Insulin Alone

Jun 2, 2018

Addition of sglt2 inhibitor (canagliflozin or dapagliflozin) as add-on therapy shows benefits in patients treated with insulin.

Current standards of diabetes care recommend the use of sodium glucose cotransporter (SGLT2) inhibitors in conjunction with insulin when glycemic goals are not reached with insulin monotherapy. A recent systematic review and meta-analysis, showed SGLT2 inhibitors are useful as both monotherapy and adjunctive diabetes treatment. Analysis of this class revealed significant reductions in HbA1c, fasting blood glucose, insulin dosage, and body weight.

Various studies have shown that addition of SGLT2 inhibitors can minimize insulin-associated weight gain and hypoglycemia all while reducing overall insulin requirements. However, according to a recent study, further examples of the benefits of SGLT2 inhibitors are lacking.

Harris et al. sought to evaluate the impact of adjunctive SGLT2 inhibitor use in patients treated with insulin with data derived from a web-based diabetes-specific electronic medical record from February 2014 to December 2016. While several SGLT2 inhibitors are currently available on the market, this study focused solely on the addition of either canagliflozin or dapagliflozin to the patient’s current treatment regimen. Ultimately, 411 patients with a HbA1c >7% were enrolled.

Statistical analysis, by way of multiple regression analysis, yielded significant results. Overall, following initiation of either SGLT2 inhibitor, significant reductions in HbA1c (p < 0.00), insulin dose, systolic blood pressure (p ≤ 0.00), diastolic blood pressure (p ≤ 0.00) and weight (p ≤ 0.00) were noted by 3 and 6 months for both canagliflozin and dapagliflozin.

A focus of the study was to determine the extent of insulin dose reduction with dual therapy. Patients on high insulin regimen (defined as >100 IU/day) showed striking results (shown below).


SGLT2 Inhibitor Insulin Dose (IU/day) Change from baseline at 3-month post initiation Change from baseline at 6-month post initiation

(N = 290)a

101-200 -17.22 (p < 0.00) -17.0 (p < 0.00)

(N = 121)b

>200 -77.2 (p = 0.02) -71.0 (p = 0.03)

Note: Significant insulin dose reductions were seen only with: (a) canagliflozin with 101-200 IU/day and (b) dapagliflozin with >200 IU/day. No significant reductions found at 0-100 IU/day for either treatment group.

Overall, data gleaned from this study confirms and supplements existing knowledge, ultimately providing additional evidence to support the use of SGLT2 inhibitors as an add-on therapy in patients unable to achieve glycemic control with insulin alone.

Practice Pearls:

  • In patients struggling to achieve glycemic goals, consider adjunct treatment with an SGLT2 inhibitor.
  • Weight gain associated with insulin treatment may be curtailed with agents from this drug class.
  • Evidence has shown that the combination of SGLT2 inhibitors and insulin may lead to significant hypoglycemia; however, this study did not note such an occurrence, which might suggest the need for further studies.

Kaytie A. Weierstahl, Pharm.D. Candidate, LECOM School of Pharmacy

Harris, S., Mequanint, S., Miller, K., Reichert, S., and Spaic, T. When Insulin Therapy Fails: The Impact of SGLT2 Inhibitors in Patients With Type 2 Diabetes. Diabetes Care. 40.10 (2018): e141-e142. https://doi.org/10.2337/dc17-0744.

Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2018. American Diabetes Association. Diabetes Care. 41(Supplement 1): S73-S85. http://care.diabetesjournals.org/content/41/Supplement_1/S73