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The efficacy and safety of SGLT2 inhibitors for adjunctive treatment of type 1 diabetes: a systematic review and meta-analysis.

ABSTRACT: To assess the efficacy and safety of the SGLT-2 inhibitors as adjunct therapy to insulin in T1DM, clinical trials indexed in PubMed, Cochrane Library, EMbase from inception through April 5, 2016. A meta-analysis was conducted on trials of SGLT-2 inhibitors in patients with T1DM on insulin therapy using RevMan 5.3 software. Of the 371 articles identified, ten met eligibility criteria. Seven clinical trials including four randomized controlled trials and 581 patients were included. Compared with the control group, SGLT-2 inhibitors group had significantly reduced fasting plasma glucose by 0.69?mmol/L [1.32; 0.07], glycosylated hemoglobin A1C by 0.37% [0.54; 0.20], body weight by 2.54?kg [3.48; 1.60] and total daily insulin dose by 6.22 IU [8.04; 4.40]. The total incidence of adverse events (AEs), hypoglycemia, and genital and urinary infections were also similar to placebo, while an increased incidence of diabetic ketoacidosis (DKA) (n?=?16) was seen in SGLT-2 inhibitors group. The present study demonstrates that SGLT-2 inhibitors are effective as adjunct therapy to insulin in T1DM, heralding improved glycemic control, reduced body weight and total daily insulin dose without an increase in total AEs, hypoglycemia, or genital and urinary infections. However, the risk of DKA should be carefully monitored in future clinical trials.

SUBMITTER: Chen J

PROVIDER: S-EPMC5343472 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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The efficacy and safety of SGLT2 inhibitors for adjunctive treatment of type 1 diabetes: a systematic review and meta-analysis.

Chen Jiao J Fan Fang F Wang J Y JY Long Yang Y Gao C L CL Stanton R C RC Xu Yong Y

Scientific reports 20170309

To assess the efficacy and safety of the SGLT-2 inhibitors as adjunct therapy to insulin in T1DM, clinical trials indexed in PubMed, Cochrane Library, EMbase from inception through April 5, 2016. A meta-analysis was conducted on trials of SGLT-2 inhibitors in patients with T1DM on insulin therapy using RevMan 5.3 software. Of the 371 articles identified, ten met eligibility criteria. Seven clinical trials including four randomized controlled trials and 581 patients were included. Compared with t ...[more]

PMID: 28276512

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Project description:BackgroundType 2 diabetes is closely related to an increased risk of atrial fibrillation (AF) and atrial flutter (AFL). Whether sodium-glucose cotransporter 2 (SGLT2) inhibitors can attenuate AF/AFL progression remains unclear.MethodsWe searched electronic databases (PubMed, Embase and ClinicalTrials.gov) from their inception to January 2020 for trials evaluating the AF outcomes of SGLT2 inhibitors in patients with type 2 diabetes. The data search and extraction were conducted with a standardized data form and any conflicts were resolved by consensus. Relative risks (RRs) with 95% confidence intervals (CIs) were used for binary variables, and the weighed mean differences (WMDs) with the standard deviation (SDs) were applied for continuous variables.ResultsWe included data from 16 identified trials consisting of 38,335 patients with type 2 diabetes. Incorporated data demonstrated that compared to placebo, SGLT2 inhibitors significantly reduced AF/AFL (RR: 0.76; 95% CI 0.65-0.90; p = 0.001) and all-cause mortality (RR: 0.91; 95% CI 0.83-0.99; p = 0.03). AF/AFL reductions were not modified by age, body weight, glycated haemoglobin (HbA1c), or systolic blood pressure (SBP) at baseline (all p-interactions > 0.3). SGLT2 inhibitors also significantly reduced heart failure events (RR: 0.73; 95% CI 0.64-0.84; p < 0.00001), HbA1c (WMD: - 0.62%; 95% CI - 0.89 to - 0.34; p < 0.00001), body weight (WMD: - 2.12 kg; 95% CI - 2.91 to - 1.34; p < 0.00001), SBP (WMD: - 3.34 mmHg; 95% CI - 4.12 to - 2.56; p < 0.00001), and diastolic blood pressure (DBP) (WMD: - 1.11 mmHg; 95% CI - 1.62 to - 0.60; p < 0.0001). Of note, cerebrovascular events and myocardial infarction did not increase in patients taking SGLT2 inhibitors.ConclusionSGLT2 inhibitors may confer a specific AF/AFL-reduction benefit in the susceptible type 2 diabetes population, regardless of age, body weight, HbA1c, and systolic blood pressure at baseline. Such an AF/AFL-reduction benefit may be partly attributed to pharmacological effects on reductions in HbA1c, body weight, blood pressure, and the occurrence of heart failure.

Project description:IntroductionThe aim of this study was to evaluate the efficacy and safety of initial combination therapy compared with monotherapy in drug-naïve type 2 diabetes patients.MethodsMEDLINE, Embase and the Cochrane Central Register of Controlled Trials were searched for randomized clinical trials of initial combination therapy with hypoglycemic agents compared with monotherapy. Those which satisfied the search criteria were included in the meta-analysis. Weighted mean difference and relative risks were calculated.ResultsA total of 36 studies were included in the meta-analysis. Compared with metformin monotherapy, initial combination therapy with metformin plus another anti-diabetes drug exhibited significant reductions in glycated hemoglobin (HbA1c) (p < 0.001). Most of the combination therapies had a similar risk of hypoglycemia (p > 0.05), with the exception of combinations of sulfonylurea/glinide and metformin or combinations of thiazolidinedione and metformin. Compared with dipeptidyl peptidase-4 (DPP-4) inhibitor monotherapy, initial combination therapy with DPP-4 inhibitor plus another anti-diabetes drug showed a significant decrease in HbA1c (p < 0.001) and a similar risk of hypoglycemia (p > 0.05). Compared with monotherapy with other anti-diabetes drugs, initial combination therapies also resulted in significant HbA1c reductions, a similar risk of hypoglycemia and similar risks of other adverse events.ConclusionCompared with monotherapy, all initial combination therapies resulted in significant HbA1c reductions. Compared with metformin monotherapy, initial combination therapies with DPP-4 inhibitors plus metformin, sodium/glucose cotransporter 2 inhibitors and metformin, respectively, were associated with similar risks of hypoglycemia, but initial combination therapies with sulfonylurea plus metformin, thiazolidinedione and metformin, respectively, were associated with higher risks of hypoglycemia.FundingAstraZeneca Ltd. (China).Trial registrationRegistration number CRD42017060717 in PROSPERO.

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The efficacy and safety of SGLT2 inhibitors for adjunctive treatment of type 1 diabetes: a systematic review and meta-analysis.

Publications

The efficacy and safety of SGLT2 inhibitors for adjunctive treatment of type 1 diabetes: a systematic review and meta-analysis.

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