Introduction
Methods
Searched Databases and Search Strategies
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Sitagliptin versus canagliflozin and diabetes mellitus
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Dipeptidyl peptidase-4 inhibitor and canagliflozin
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Sitagliptin and sodium-glucose transport (SGLT-2) inhibitors
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Dipeptidyl peptidase-4 inhibitor and sodium-glucose transport (SGLT-2) inhibitors
Criteria for Inclusion
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They were randomized controlled trials or observational cohorts comparing sitagliptin (100 mg) with canagliflozin (100 mg or 300 mg or both) in patients with T2DM.
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They reported adverse drug events among their clinical outcomes.
Criteria for Exclusion
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They were meta-analysis, review articles, review of the literatures, case–control studies, letters of correspondence.
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They did not compare sitagliptin (100 mg) with canagliflozin.
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They did not report adverse drug events among their clinical outcomes.
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They included patients with type 1 diabetes mellitus.
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They were repeated studies involving the same data.
Outcomes and Follow-up
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Any adverse events
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Adverse events leading to drug discontinuation
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Serious adverse events (potentially fatal and life-threatening)
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Urinary tract infections
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Hypoglycemia
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Genital mycotic infections
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Adverse events related to hypovolemia
Studies | Outcomes reported | Follow-up period |
---|---|---|
Lavalle-González [9] | Any AE, AE leading to drug discontinuation, serious AE, UTI, genital mycotic infection in men and women, postural dizziness, orthostatic hypotension | 52 weeks |
Rodbard [10] | Any AE, AE leading to drug discontinuation, serious AE, UTI, genital mycotic infection in men and women, documented hypoglycemia, severe hypoglycemia | 26 weeks |
Rosenstock [11] | Any AE, AE leading to drug discontinuation, serious AE, UTI, vulvovaginal mycotic infection, symptomatic hypoglycemia, AE related to hypovolemia, symptomatic genital infection | 12 weeks |
Schernthaner [12] | Any AE, AE leading to drug discontinuation, serious AE, death, UTI, genital mycotic infection in men and women, postural dizziness, orthostatic hypotension | 52 weeks |
Shao [13] | Any AE, AE leading to drug discontinuation, genital mycotic infection, UTI, AE related to hypovolemia, hypoglycemia | 24 weeks |
Data Extraction and Review
Statistical Analysis
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The Q statistic test whereby a P value greater than 0.05 was considered statistically significant
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The I2 statistic test whereby a low level of heterogeneity was denoted by a low I2 value
Compliance with Ethics Guidelines
Results
Searched Outcomes
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They were a review of the literature (2).
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They were letters of correspondence (2).
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They did not report the expected clinical outcomes (4).
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They did not compare sitagliptin with 100 or 300 mg canagliflozin (12).
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They were repeated studies involving similar data (16).
General Features
Studies | No. of patients treated with 100 mg CANA (n) | No. of patients treated with 300 mg CANA (n) | No. of patients treated with sitagliptin 100 mg (n) | Types of study | Background drugs |
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Lavalle-González [9] | 368 | 367 | 366 | RCT | Metformin monotherapy |
Rodbard [10] | 108 | – | 108 | RCT | Metformin and sitagliptin |
Rosenstock [11] | 64 | 64 | 65 | RCT | Metformin |
Schernthaner [12] | – | 377 | 378 | RCT | Metformin + sulfonylurea |
Shao [13] | – | 22 | 35 | Retrospective cohort | – |
Total no. of patients (n) | 540 | 830 | 952 |
Baseline Features of the Participants
Studies | Age (years) | Male (%) | HbA1c (%) | Duration of DM (years) | FPG (mmol/L) |
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C1/C3/S | C1/C3/S | C1/C3/S | C1/C3/S | C1/C3/S | |
Lavalle-González [9] | 55.5/55.3/55.5 | 47.3/45.0/47.0 | 7.9/7.9/7.9 | 6.7/7.1/6.8 | 9.3/9.6/9.4 |
Rodbard [10] | 57.4/–/57.5 | 61.7/–/51.9 | 8.5/–/8.4 | 9.8/–/10.1 | 10.3/–/10.0 |
Rosenstock [11] | 51.7/55.2/51.7 | 56.0/44.0/58.0 | 7.83/7.69/7.73 | 6.1/5.8/5.6 | – |
Schernthaner [12] | –/56.6/56.7 | –/45.1/43.1 | –/8.1/8.1 | –/9.4/9.7 | –/9.4/9.2 |
Shao [13] | –/45.2/45.5 | –/59.1/60.0 | –/9.4/9.3 | –12.6/9.4 | – |
Sitagliptin (100 mg) Versus 100 mg Canagliflozin
Outcomes assessed | RR with 95% CI | P value | I2 (%) |
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SITA 100 mg versus CANA 100 mg | |||
Any adverse event | 1.10 [1.00–1.21] | 0.05 | 21 |
AE leading to drug discontinuation | 1.20 [0.67–2.16] | 0.54 | 25 |
Serious AE | 0.90 [0.49–1.66] | 0.73 | 0 |
Urinary tract infection | 1.26 [0.77–2.08] | 0.36 | 0 |
Genital mycotic infection (overall) | 4.32 [2.11–8.83] | 0.0001 | 0 |
Hypoglycemia | 1.01 [0.30–3.43] | 0.99 | 36 |
AE related to hypovolemia | 1.76 [0.52–5.94] | 0.36 | 0 |
SITA 100 mg versus CANA 300 mg | |||
Any adverse event | 1.18 [0.93–1.49] | 0.17 | 85 |
AE leading to drug discontinuation | 1.14 [0.87–1.49] | 0.33 | 38 |
Serious AE | 0.95 [0.61–1.47] | 0.82 | 0 |
Urinary tract infection | 0.80 [0.52–1.23] | 0.31 | 0 |
Genital mycotic infection (overall) | 4.51 [2.67–7.63] | 0.00001 | 0 |
Hypoglycemia | 0.94 [0.32–2.78] | 0.91 | 0 |
AE related to hypovolemia | 1.08 [0.36–3.25] | 0.89 | 6 |