Safety and efficiency of SGLT2 inhibitor combining with insulin in subjects with diabetes

Abstract

Background:We aimed to assess the safety and efficiency of the novel sodium glucose co-transporter 2 (SGLT2) inhibitor in combinations with insulin for type 1 and type 2 diabetes mellitus (T1DM and T2DM).Methods:We searched Medline, Pubmed, Embase, and the Cochrane Collaboration Library from January 2010 to December 2016 without restriction of language. FDA data and Clinical Trials (http://www.clinicaltrials.gov) were also searched. Study selection, data extraction, and evaluation of risk of bias were performed by 2 persons independently. The risk of bias was assessed by Cochrance System Evaluate Method and Q test was used to evaluate the heterogeneity between studies. We used random effect model to analyze the results by Revman 5.3. This meta-analysis has been registered at online public registry PROSPERO (registration number is: CRD42017054718).Results:Nine trials including 3069 patients were analyzed. Compared with control group, SGLT2 inhibitor produced absolute reduction in glycosylated hemoglobin A1c (HbA1c) (MD −1.35%, 95% confidence interval [CI] [−2.36 to −0.34], P = .009), fasting plasma glucose (FPG) (MD −1.01 mmol/L, 95%CI [−1.98 to 0.04], P = .04), insulin dosage (MD −4.85 U/24 hours, 95%CI [−7.42 to −2.29], P = .002), and body weight (MD −2.30 kg, 95%CI [−3.09 to −1.50], P < .00001). But the risk of hypoglycemia (OR 1.18, 95%CI [0.86, 1.61], P = . 30) and urinary tract infection (UTI) (OR 1.34, 95%CI [0.79, 2.27], P = .28) were proved as no difference and genital tract infection (GTI) with SGLT2 inhibitors was higher than control group (OR 2.96, 95%CI [1.05, 8.37], P = .04), in which cases were mild and responded to the therapy. According to the subgroup analysis, SGLT2 inhibitors had a similar effect in effective factors of both T1DM and T2DM, but the risk of GTI mainly increased in T2DM versus T1DM (T1DM OR 0.27 [0.01, 7.19], P = .43 vs T2DM OR 4.28 [2.00, 9.16], P = .0002).Conclusion:SGLT2 inhibitors have improved the HbA1c, FPG, and body weight when combined with insulin and decreased the dose of insulin without increasing the risk of hypoglycemia. However, SGLT2 inhibitor was proved to be related to the events of GTI, despite SGLT2 inhibitors appeared to be well tolerated. We suggest that more monitoring should be done to prevent the events of GTI, and more randomized controlled trials should be planned next step.

Safety and efficacy of sodium glucose co‐transporter 2 inhibitors combined with insulin in adults with type 1 diabetes: A meta‐analysis of randomized controlled trials

“…Because SGLT2 inhibitors decreased total insulin dose, hypoglycemia induced by high insulin dose was unlikely to happen in theory. In our analysis, combination therapy of SGLT2 inhibitors and insulin indeed did not increase the rate of hypoglycemia, and the same conclusion was also made for SH, which is consistent with other meta‐analysis . In addition, for cardiovascular disease, bone fracture and all‐cause mortality, due to most included trials being of short duration, patients administrated SGLT2 inhibitors did not present an increased risk.…”

“…It is a pity that this analysis just performed a rough discussion on high and low doses, along with a small sample size and poor information on adverse events. 5 Compared with the previous reports, [5][6][7][8][9] the present analysis not only presented so far the largest sample size and more extracted parameters, but also provided a more detailed subgroup analysis for high, medium and low doses on the safety and efficacy of SGLT2 inhibitors.…”

“…Compared with the previous reports, the present analysis not only presented so far the largest sample size and more extracted parameters, but also provided a more detailed subgroup analysis for high, medium and low doses on the safety and efficacy of SGLT2 inhibitors.…”

Sodium‐glucose co‐transporter‐2 inhibitors as add‐on therapy to insulin for type 1 diabetes mellitus: Systematic review and meta‐analysis of randomized controlled trials

“…Two other meta‐analyses have been reported, but these differed from the present meta‐analysis in the following two ways. First, both previous studies analysed a small number of papers and did not detect significant differences for any event because of insufficient power.…”

The Safety and Efficacy of SGTL2 Inhibitors in Diabetes Mellitus Management

“…That being said it has been demonstrated that SGLT2 inhibitor use within T1DM can lead to decreased insulin requirements of up to 16%, this is particularly of benefit in the young who often omit insulin for fear of its anabolic effects (7). In addition in T1DM it was found that use of compounds such as dapagliflozin could increase glucosuriaby 88mg/day and a recent meta-analysis found that the improvements SGLT2i could have on DM management when used as an add on therapy to insulin were dose independent with body weight reductions increased in T2DM patients versus T1DM and improved glucose control in particularly eastern Asian patients (13).…”