Author + information
- Received February 14, 2018
- Revision received May 1, 2018
- Accepted May 10, 2018
- Published online September 24, 2018.
- Caroline K. Kramer, MD, PhDa,b,
- Chang Ye, MSca,
- Sara Campbell, MDa and
- Ravi Retnakaran, MDa,b,c,∗ ()
- aLeadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Canada
- bDivision of Endocrinology, University of Toronto, Toronto, Canada
- cLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada
- ↵∗Address for correspondence:
Dr. Ravi Retnakaran, University of Toronto, Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, 60 Murray Street, Suite L5-025, Mailbox-21, Toronto, Ontario M5T 3L9, Canada.
Objectives The authors conducted a systematic review and network meta-analysis of placebo-controlled, randomized clinical trials in the post–Food and Drug Administration (FDA) guidance era to formally compare the effects of 3 new classes of glucose-lowering drugs on hospitalization for heart failure (HF) in type 2 diabetes mellitus.
Background The 2008 FDA Guidance for Industry launched an era of cardiovascular outcome trials for new glucose-lowering drugs in T2DM, including glucagon-like peptide (GLP)-1 agonists, dipeptidyl peptidase (DPP)-4 inhibitors, and sodium glucose co-transporter (SGLT)-2 inhibitors.
Methods We searched Embase, PubMed, Cochrane Library, and clinicaltrials.gov between December 1, 2008, and November 24, 2017, for randomized placebo-controlled trials, and performed network meta-analyses by Bayesian approach using Markov-chain Monte Carlo simulation method to compare the effects of glucose-lowering drugs on risk of HF hospitalization and estimate the probability that each treatment is the most effective.
Results Nine studies were identified, yielding data on 87,162 participants. In the network meta-analysis, SGLT-2 inhibitors yielded the greatest risk reduction for HF hospitalization compared with placebo (relative risk [RR]: 0.56; 95% CrI [credibility interval]: 0.43 to 0.72). Moreover, SGLT-2 inhibitors were associated with significant risk reduction in pairwise comparisons with both GLP-1 agonists (RR: 0.59; 95% CrI: 0.43 to 0.79) and DPP-4 inhibitors (RR: 0.50; 95% CrI: 0.36 to 0.70). Ranking of the classes revealed 99.6% probability of SGLT-2 inhibitors being the optimal treatment for reducing the risk of this outcome, followed by GLP-1 agonists (0.27%) and DPP-4 inhibitors (0.1%).
Conclusions Current evidence suggests that SGLT-2 inhibitors are more effective than either GLP-1 agonists or DPP-4 inhibitors for reducing the risk of hospitalization for HF in type 2 diabetes mellitus.
- heart failure
- dipeptidyl peptidase-4 inhibitor
- glucagon-like peptide-1 agonist
- sodium glucose co-transporter-2 inhibitor
- type 2 diabetes
This study was supported by intramural funds from Mount Sinai Hospital. Dr. Kramer holds the Banting and Best Diabetes Centre New Investigator Award and the Canadian Diabetes Association Clinician-Scientist Award; and has received grants from Boehringer Ingelheim. Dr. Retnakaran is supported by a Heart and Stroke Foundation of Ontario Mid-Career Investigator Award; holds the Boehringer Ingelheim Chair in Beta-cell Preservation, Function and Regeneration at Mount Sinai Hospital; has received grants from Novo Nordisk, Boehringer Ingelheim, and Merck; and has received personal fees from Novo Nordisk, Eli Lilly, Takeda, Sanofi, and Merck. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received February 14, 2018.
- Revision received May 1, 2018.
- Accepted May 10, 2018.
- 2018 American College of Cardiology Foundation