Effects of sodium‐glucose cotransporter (SGLT) inhibitors in addition to insulin therapy on glucose control and safety outcomes in adults with type 1 diabetes: A meta‐analysis of randomized controlled trials

Background: Several clinical trials have tested the safety profile of sodium-glucose co-transport inhibitors’ (SGLTis) in adult type 1 diabetes mellitus (T1DM) patients. However, no systematic review has yet compared its variation between large and low dose SGLTis. Henceforth, a review protocol is proposed here to review it. Methods: Different electronic databases will be searched for randomized-controlled trials (published in the English language) studying the above objective, irrespective of their publication date. After selecting the eligible trials, their data on the study design, population characteristics, compared interventions, and outcomes of interest will be extracted. Then, utilizing the Cochrane tool, each trial's risk of selection bias, detection bias, performance bias, attrition bias, reporting bias, and other bias will be judged. Next, depending on clinical heterogeneity among the trials, a random-effect or fixed-effect model meta-analysis will be used to compare the respective outcomes. Via the Chi2 and I2 statistics, the statistical inconsistency among the trials will be estimated. When this is substantial, subgroup analysis will follow. Publication bias will be evaluated by funnel plots and Egger’s test. A sensitivity analysis will be done to check different assumptions. If a quantitative juxtaposition is not possible, a narrative reporting will ensue. Conclusion: The proposed study will perform a dose-wise juxtaposition of the safety profile of SGLTis in insulin-treated T1DM patients. Registration: Prospective Register of Systematic Reviews (PROSPERO) (Registration no. CRD42019146578)

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A Systematic Review and Meta-Analysis of Randomized Controlled Trials Comparing the Safety of Dapagliflozin in Type 1 Diabetes Patients

Iranian Journal Of Health Sciences ◽

10.18502/jhs.v8i2.4028 ◽

2020 ◽

Author(s):

Sumanta Saha ◽

Sujata Saha

Keyword(s):

Systematic Review ◽

Type 1 Diabetes ◽

Side Effects ◽

Randomized Controlled Trials ◽

Meta Analysis ◽

Random Effect ◽

Risk Of Bias ◽

Controlled Trials ◽

Randomized Controlled

Background and Purpose: The dapagliflozin’s safety profile in insulin-treated adult type-1 diabetes mellites (T1DM) patients remains poorly explored. Therefore, this systematic review and meta-analysis compared the risk of all-cause side effects, study discontinuation of participants due to side effects, urinary tract infection (UTI), diabetic ketoacidosis, and hypoglycemia between dapagliflozin 10 mg and dapagliflozin 5 mg, dapagliflozin 10 mg and placebo, and dapagliflozin 5 mg and placebo.Materials and Methods: Parallel-arm randomized controlled trials juxtaposing the above outcomes between the afore-mentioned interventions were eligible for inclusion in this study and were searched in PubMed, Embase, and Scopus. Utilizing the Cochrane tool, the risk of bias was assessed in the recruited trials. Finally, by random-effect meta-analysis, each outcome was compared among the above interventions, and the risk ratio was estimated.Results: Four trials of varying length (1-52 weeks) sourcing data from almost 1760 participants from about 32 nations were reviewed. Overall, the trials had a low or unclear risk of bias, and only one was at a high risk of bias. Compared to the placebo, the risk of side effects was higher in those treated with dapagliflozin 5 mg (RR=1.10; 95% CI=1.02-1.18; p=0.014; I2=0%). UTI risk was less with the 10mg dapagliflozin than its lower dose (RR=0.50; 95% CI=0.32-0.79; p-value=0.003; I2=0%). All the remaining comparisons were statistically not significantly different between the juxtaposed intervention pairs.Conclusion: In contrast to placebo, dapagliflozin 5mg increased the risk of overall adversities in insulin-treated type-1 diabetes, and dapagliflozin 10 mg had a reduced risk of UTI than its 5mg preparation.

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