0

The full content of Annals is available to subscribers

Subscribe/Learn More  >
Reviews |

Sodium–Glucose Cotransporter 2 Inhibitors for Type 2 Diabetes: A Systematic Review and Meta-analysis

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; and Apostolos Tsapas, MD, PhD, MSc
[+] Article and Author Information

From Aristotle University Thessaloniki, Thessaloniki, Greece, and University of Oxford, Oxford, United Kingdom.

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, atsapas@auth.gr.

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.


Ann Intern Med. 2013;159(4):262-274. doi:10.7326/0003-4819-159-4-201308200-00007
Text Size: A A A

Background: Sodium–glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs.

Purpose: To assess the efficacy and safety of SGLT2 inhibitors in adults with type 2 diabetes.

Data Sources: MEDLINE, EMBASE, and the Cochrane Library from inception through April 2013 without language restrictions; regulatory authorities' reports; and gray literature.

Study Selection: Randomized trials comparing SGLT2 inhibitors with placebo or other medication for type 2 diabetes.

Data Extraction: 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.

Data Synthesis: 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.

Limitation: Most trials were rated as high risk of bias because of missing data and last-observation-carried-forward methods.

Conclusion: 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.

Primary Funding Source: None.

Figures

Grahic Jump Location
Appendix Figure.

Summary of evidence search and selection.

EMA = European Medicines Agency; FDA = U.S. Food and Drug Administration.

Grahic Jump Location
Grahic Jump Location
Figure 1.

Weighted mean difference in change in hemoglobin A1c level from baseline: SGLT2 inhibitors versus placebo.

Results are from IV random-effects meta-analysis. IV = inverse variance; SGLT2 = sodium–glucose cotransporter 2.

* Reference 48 includes 2 randomized trials of dapagliflozin at doses of 5 mg (study 1) and 10 mg (study 2).

Grahic Jump Location
Grahic Jump Location
Figure 2.

Weighted mean difference in change in hemoglobin A1c level from baseline: SGLT2 inhibitors versus other antidiabetic drugs.

Results are from IV random-effects meta-analysis. IV = inverse variance; SGLT2 = sodium–glucose cotransporter 2.

* Reference 48 includes 2 randomized trials of dapagliflozin at doses of 5 mg (study 1) and 10 mg (study 2).

Grahic Jump Location

Tables

References

Letters

CME Activities are only available to ACP members and Individual Annals subscribers. If you are a member or a subscriber please sign in. Otherwise please become a member or subscribe to Annals.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Comments

Submit a Comment
Submit a Comment

Summary for Patients

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.

Toolkit

Buy Now

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Advertisement
Related Articles
Related Point of Care
Topic Collections
PubMed Articles
Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.
(Required)
(Required)