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SGLT2 Inhibitors in Treatment of Type 1

Feb 17, 2018
 

Meta-analysis explores safety and efficacy of sodium-glucose co-transporter 2 inhibitors in patients with type 1 diabetes.

Individuals living with type 1 diabetes most of their lives are exposed to numerous comorbidities that ultimately lead to a significant decrease in estimated life expectancy by approximately 12 years, as we have seen with former studies conducted on the subject. Moreover, considering that patients with type 1 are treated with insulin as their main option for managing blood sugar levels, these individuals have augmented peril to experience serious dose-dependent side-effects such as hypoglycemia or weight gain. Use of oral medications for management of T1D has been investigated before without much success, save for oral pramlintide. When used in combination with insulin for type 2, the new kids in town, SGLT2 inhibitors, have shown to decrease the insulin need, weight gain, and hypoglycemia. But, would the similar effects be produced in patients with type 1 following the combination therapy? To establish a place for SGLT2’s in type 1 diabetes, researchers conducted a systematic review and meta-analysis of randomized controlled trials.

Their findings were recently published in Diabetes Research and Clinical Practice.

El Masri and colleagues conducted a literature review of PubMed, Embase, Scopus, Web of Science and Cochrane library to screen for potential RCTs concerning the use of SGLT2-i in T1D to be included into the meta analysis. Studies that included patients with type 2, or those studies that did not include original data were excluded from the systematic review. Four randomized controlled trials were included with the primary outcome of the analysis being to establish the extent SGLT2-i lead to changes in body weight, insulin need, and HbA1c levels. Rate of adverse events, DKA, and hypoglycemia were the secondary outcomes of the study.

Four RCTs that were included in the study assessed canagliflozin, empagliflozin and sotagliflozin as add-ons to insulin, and dapagliflozin as an add-on to liraglutide and insulin. At conclusion of the analysis, investigators found that individuals treated with SGLT2 inhibitors plus insulin had significant decrease of their A1c levels when compared to placebo; weighted mean difference of 0.39. The highest benefit was observed with dapagliflozin, WMD of 0.66. When assessing body weight changes, all studies showed a statistical significant reduction in weight with SGLT2’s, WMD 2.76.  The greatest weight reduction was noted with canagliflozin, WMD of 4.39. Lastly, with respect to total daily insulin dose, all treatments led to statistically significant reduction.  Canagliflozin and dapagliflozin led to a significant decrease of insulin dose, as shown by WMD 5.03. Empagliflozin led to a decreased need of insulin dosage between 0.08 and 0.11 units/kg, p-value <0.05; while sotagliflozin reduced insulin by 15.3% from baseline, p-value of 0.002. When looking at secondary outcomes, each of the studies included did not report a significant difference of hypoglycemia risk, incidence of adverse events or increase in the frequency of DKA episodes.

The results of the meta analysis presented by El Marsi et al. provide promising evidence of SGLT2-i use in type 1 diabetes.  =Not only was there benefit in lowering insulin dosage need, reducing body weight, and bettering A1c outcomes in individuals with T1D, the addition of SGLT2-i did not result in significant increase in adverse reactions, hypoglycemia, or incidence of DKA. Prior to accepting the results from this systematic review on a large scare, bigger-prospective studies with longer durations will need to be completed to evaluate the usefulness of SGLT2’s in T1D on a population level.   Regardless of the limitation of including only 4 RCTs into this systemic review, compelling results that we have seen with this review should instigate researchers to further investigate the use of SGLT2 inhibitors in the treatment of type 1 diabetes.

Practice Pearls:

  • The addition of SGLT2 inhibitors to insulin resulted in reduction of baseline HbA1c levels, decreased insulin dose needed, and lowering of body weight in patients with type 1.
  • SGLT2-i did not increase the risk of DKA, hypoglycemic episodes, or adverse events.
  • Larger, prospective RCTs are needed to explore a true value of routine SGLT2-i use as an add-on therapy to insulin in individuals with type 1 diabetes.

References:

Dana El Masri, Samiran Ghosh, Linda Jaber.  “Safety and Efficacy of Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors in Type 1 Diabetes: A Systematic Review and Meta Analysis.” Diabetes Research and Clinical Practice. 2018.  http://www.diabetesresearchclinicalpractice.com/action/consumeSharedSessionAction?JSESSIONID=aaad8qvrKF2Y5dkLI8mfw&MAID=0S01sHlagcvzV9PsFQ4MOw%3D%3D&SERVER=WZ6myaEXBLGZpQFlLdJmhw%3D%3D&ORIGIN=196588977&RD=RD&rtc=0.  Accessed Jan 2018.

Shona Livingstone, Daniel Levin, Helen Looker, et al. “Estimated life expectancy in a Scottish cohort with type 1 diabetes, 2008-2010.” JAMA 2015.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4426486/. Accessed on Jan 2018.

Lamija Zimic PharmD(c), University of South Florida, College of Pharmacy