Comparative safety of the sodium glucose co-transporter 2 (SGLT2) inhibitors: a systematic review and meta-analysis.

BMJ Open
Jennifer R DonnanJohn-Michael Gamble

Abstract

To estimate the association between the use of sodium glucose co-transporter-2 (SGLT2) inhibitors and postmarket harms as identified by drug regulatory agencies. We conducted a systematic review and meta-analysis of randomised controlled trials (RCT). Six large databases were searched from inception to May 2018. Random effects models were used to estimate pooled relative risks (RRs). SGLT2 inhibitors, compared with placebo or active comparators. Acute kidney injury (AKI), diabetic ketoacidosis (DKA), urinary tract infections (UTI), bone fractures and lower limb amputations. We screened 2418 citations of which 109 were included. Most studies included one of four SGLT2 inhibitors, dapagliflozin, canagliflozin, empagliflozin and ipragliflozin. When compared with placebo, SGLT2 inhibitors were found to be significantly protective against AKI (RR=0.59; 95% CI 0.39 to 0.89; I2=0.0%), while no difference was found for DKA (RR 0.66; 95% CI 0.30 to 1.45, I2=0.0%), UTI (RR 1.02; 95% CI 0.95 to 1.09, I2=0.0%) or bone fracture (RR 0.87; 95% CI 0.69 to 1.09, I2=1.3%). Three studies reported on amputation, with one finding a significant increase risk. No increased risk for either outcome was found when compared with active controls. Subgroup...Continue Reading

References

Sep 27, 2000·Journal of Clinical Epidemiology·D MoherA Liberati
Sep 6, 2003·BMJ : British Medical Journal·Julian P T HigginsDouglas G Altman
Jul 7, 2007·BMC Medical Research Methodology·Yoon K LokeUNKNOWN Cochrane Adverse Effects Methods Group
Dec 31, 2008·Diabetes Care·James F ListFred T Fiedorek
Jul 23, 2009·Annals of Internal Medicine·David MoherUNKNOWN PRISMA Group
Oct 20, 2011·BMJ : British Medical Journal·Julian P T HigginsUNKNOWN Cochrane Statistical Methods Group
Jan 5, 2012·BMJ : British Medical Journal·Beth HartLisa Bero
May 9, 2012·International Journal of Technology Assessment in Health Care·Andra MorrisonDanielle Rabb
May 17, 2012·Systematic Reviews·Sara KhanguraDavid Moher
May 15, 2013·Diabetes, Obesity & Metabolism·H J Lambers HeerspinkJ List
Jul 11, 2013·Diabetes Therapy : Research, Treatment and Education of Diabetes and Related Disorders·Tim HeiseKlaus Dugi
Aug 6, 2013·Diabetes, Obesity & Metabolism·J P H WildingUNKNOWN Dapagliflozin 006 Study Group
Jun 21, 2014·The Lancet. Diabetes & Endocrinology·Martin RidderstråleUNKNOWN EMPA-REG H2H-SU trial investigators

❮ Previous
Next ❯

Citations

May 3, 2019·Diabetes, Obesity & Metabolism·Richard E Gilbert, Kevin E Thorpe
Mar 5, 2020·Diabetes Therapy : Research, Treatment and Education of Diabetes and Related Disorders·Sanjay KalraJignesh K Ved
Nov 9, 2019·The International Journal of Lower Extremity Wounds·Eleni PapadokostakiEvangelos N Liberopoulos
May 22, 2020·Diabetes, Obesity & Metabolism·Clare ArnottBruce Neal
Jul 11, 2020·Expert Opinion on Drug Discovery·Karl Sebastian JohanssonMikkel Bring Christensen
Jul 28, 2020·Current Osteoporosis Reports·Kristen Jackson, Kendall F Moseley
Dec 5, 2019·Diabetic Medicine : a Journal of the British Diabetic Association·S JavedR A Malik
Feb 1, 2020·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Jose Luis GórrizMaria Jose Soler
Sep 15, 2020·Modern Rheumatology·Hiroyuki NakamuraTatsuya Atsumi
Sep 1, 2020·The New England Journal of Medicine·Milton PackerUNKNOWN EMPEROR-Reduced Trial Investigators
Jun 20, 2020·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Takahiro Masuda, Daisuke Nagata
Sep 17, 2019·World Journal of Diabetes·Silvia Costantini, Caterina Conte
Aug 28, 2020·World Journal of Diabetes·Petra Grubić RotkvićIvana Ćelap
Oct 8, 2020·Diabetes Therapy : Research, Treatment and Education of Diabetes and Related Disorders·Ajitesh RoyUNKNOWN Working Group of the Endocrine Society of Bengal
Oct 24, 2020·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Tamara Y MilderJerry R Greenfield
Dec 2, 2020·International Journal of Clinical Pharmacy·Ai-Yu Yang, Hung-Chun Chen
Feb 17, 2021·Deutsche medizinische Wochenschrift·Melina MertensKarsten Müssig
Nov 24, 2020·Cardiovascular Diabetology·Francesco GiorginoAnna Solini
Feb 9, 2021·Therapeutic Advances in Drug Safety·Ryan PelletierJohn-Michael Gamble
Feb 11, 2021·The Journal of the American Osteopathic Association·Donald S NelinsonRobert J Chilton
Mar 4, 2021·European Heart Journal Supplements : Journal of the European Society of Cardiology·Gloria Vassiliki' CoutsoumbasGiuseppe Di Pasquale
Apr 30, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Ahmed S AhmedRasha A Elsisy
May 1, 2021·International Journal of Molecular Sciences·Antonia DonatJohannes Keller
Jun 3, 2021·Journal of Clinical Medicine·Henri LuRoger Hullin

❮ Previous
Next ❯

Methods Mentioned

BETA
amputations
amputation

Clinical Trials Mentioned

NCT01422876

Software Mentioned

DistillerSR
R
ProQuest
CANVAS

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.