Despoina Vasilakou, MD, MSc; Thomas Karagiannis, MD, MSc; Eleni Athanasiadou, MSc; Maria Mainou, MD; Aris Liakos, MD; Eleni Bekiari, MD, PhD; Maria Sarigianni, MD, PhD, MSc; David R. Matthews, MD, DPhil; Apostolos Tsapas, MD, PhD, MSc
Note: All authors had full access to all of the data in the study and bear responsibility for the integrity of the data analysis.
Potential Conflicts of Interest: Dr. Matthews: Other: Novo Nordisk, Boehringer Ingelheim, AstraZeneca, SB Communications, Merck, Takeda Chemical Industries, Johnson & Johnson, GlaxoSmithKline, Servier. Dr. Tsapas: Grant: Boehringer Ingelheim, Novartis, Novo Nordisk, Sanofi-Aventis; Other: Novo Nordisk. All other authors have no disclosures. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-0277.
Requests for Single Reprints: Apostolos Tsapas, MD, PhD, MSc, Second Medical Department, Aristotle University Thessaloniki, 49 Konstantinoupoleos Street, 54642 Thessaloniki, Greece; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Vasilakou, Karagiannis, Mainou, Liakos, Bekiari, Sarigianni, and Tsapas and Ms. Athanasiadou: Second Medical Department, Aristotle University Thessaloniki, Hippokratio General Hospital, 49 Konstantinoupoleos Street, 54642 Thessaloniki, Greece.
Dr. Matthews: Harris Manchester College, Mansfield Road, Oxford OX1 3TD, United Kingdom.
Author Contributions: Conception and design: D. Vasilakou, T. Karagiannis, E. Athanasiadou, E. Bekiari, M. Sarigianni, D.R. Matthews, A. Tsapas.
Analysis and interpretation of the data: D. Vasilakou, T. Karagiannis, E. Athanasiadou, M. Mainou, A. Liakos, E. Bekiari, M. Sarigianni, D.R. Matthews, A. Tsapas.
Drafting of the article: D. Vasilakou, T. Karagiannis, M. Mainou, A. Tsapas.
Critical revision of the article for important intellectual content: D. Vasilakou, T. Karagiannis, E. Athanasiadou, A. Liakos, E. Bekiari, M. Sarigianni, D.R. Matthews, A. Tsapas.
Final approval of the article: D. Vasilakou, T. Karagiannis, E. Athanasiadou, A. Liakos, E. Bekiari, M. Sarigianni, A. Tsapas.
Provision of study materials or patients: D. Vasilakou, E. Athanasiadou, A. Liakos, A. Tsapas.
Statistical expertise: D. Vasilakou, E. Athanasiadou, M. Mainou, A. Liakos, M. Sarigianni, A. Tsapas.
Administrative, technical, or logistic support: D. Vasilakou, A. Liakos.
Collection and assembly of data: D. Vasilakou, T. Karagiannis, E. Athanasiadou, A. Liakos, A. Tsapas.
Vasilakou D, Karagiannis T, Athanasiadou E, Mainou M, Liakos A, Bekiari E, et al. Sodium–Glucose Cotransporter 2 Inhibitors for Type 2 Diabetes: A Systematic Review and Meta-analysis. Ann Intern Med. 2013;159:262-274. doi: 10.7326/0003-4819-159-4-201308200-00007
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Published: Ann Intern Med. 2013;159(4):262-274.
Sodium–glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs.
To assess the efficacy and safety of SGLT2 inhibitors in adults with type 2 diabetes.
MEDLINE, EMBASE, and the Cochrane Library from inception through April 2013 without language restrictions; regulatory authorities' reports; and gray literature.
Randomized trials comparing SGLT2 inhibitors with placebo or other medication for type 2 diabetes.
Three reviewers extracted or checked data for study characteristics, outcomes of interest, and risk of bias, and 3 reviewers summarized strength of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach.
Sodium–glucose cotransporter 2 inhibitors were compared with placebo in 45 studies (n = 11 232) and with active comparators in 13 studies (n = 5175). They had a favorable effect on hemoglobin A1c level (mean difference vs. placebo, −0.66% [95% CI, −0.73% to −0.58%]; mean difference vs. active comparators, −0.06% [CI, −0.18% to 0.05%]). Sensitivity analyses incorporating unpublished data showed similar effect estimates. Compared with other agents, SGLT2 inhibitors reduced body weight (mean difference, −1.80 kg [CI, −3.50 to −0.11 kg]) and systolic blood pressure (mean difference, −4.45 mm Hg [CI, −5.73 to −3.18 mm Hg]). Urinary and genital tract infections were more common with SGLT2 inhibitors (odds ratios, 1.42 [CI, 1.06 to 1.90] and 5.06 [CI, 3.44 to 7.45], respectively). Hypoglycemic risk was similar to that of other agents. Results for cardiovascular outcomes and death were inconclusive. An imbalance in incidence of bladder and breast cancer was noted with dapagliflozin compared with control.
Most trials were rated as high risk of bias because of missing data and last-observation-carried-forward methods.
Sodium–glucose cotransporter 2 inhibitors may improve short-term outcomes in adults with type 2 diabetes, but effects on long-term outcomes and safety are unclear.
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Cardiology, Endocrine and Metabolism, Nephrology, Diabetes, Coronary Risk Factors.
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