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Lower mortality with SGLT2 inhibitors, GLP-1 agonists than DPP-IV inhibitors in diabetes
Among patients with type 2 diabetes, the use of SGLT2 inhibitors and GLP-1 receptor agonists is associated with lower risk for all-cause mortality and cardiovascular mortality vs. DPP-IV inhibitors, according to a systematic review of randomized controlled trials published in JAMA.
“Doctors are now presented with many treatment options for their patients with type 2 diabetes,” Sean L. Zheng, BM BCh, MA, MRCP, told Endocrine Today. “The focus of diabetes management has been the reduction of glycated hemoglobin levels. Recent research suggests that some of these medications may provide additional cardiovascular benefits in the short to medium term. This study provides insight in how three of the newest and most frequently used therapies compare when it comes to survival and cardiovascular disease and will allow clinicians to make better-informed decisions regarding the care of their patients with diabetes.”
In a meta-analysis, Zheng and colleagues analyzed data from 236 randomized controlled trials conducted through October 2017 assessing 258 drug-class comparisons in people with type 2 diabetes followed for at least 12 weeks (n = 176,310), including 14 trials comparing a GLP-1 receptor agonist with a DPP-IV inhibitor and eight trials comparing an SGLT2 inhibitor with a GLP-1 receptor agonist. Nine of the studies were CV outcomes trials (n = 87,162) with participants at increased risk for a CV event or who had established CVD, including EMPA-REG, CANVAS, ELIXA, LEADER, SUSTAIN-6, EXSCEL, SAVOR-TIMI 53, EXAMINE and TECOS. Primary outcome was all-cause mortality. Secondary outcomes were CV mortality, heart failure events, myocardial infarction, unstable angina and stroke. Safety endpoints were adverse events and hypoglycemia.
Researchers found that SGLT2 inhibitor use was associated with a lower risk for all-cause mortality vs. control arms across trials, with an absolute risk difference of –1% (HR = 0.8; 95% credible interval [CrI], 0.71-0.89), as were GLP-1 receptor agonists, with an absolute risk difference of –0.6% (HR = 0.88; 95% CrI, 0.81-0.94), whereas DPP-IV inhibitors were not associated with risk reduction compared with control arms (HR = 1.02; 95% CrI, 0.94-1.11).
Additionally, SGLT2 inhibitors were associated with a lower risk for all-cause mortality vs. DPP-IV inhibitors, with an absolute risk reduction of –0.9% (HR = 0.78; 95% CrI, 0.68-0.9), as were GLP-1 receptor agonists, with an absolute risk difference of –0.5% vs. DPP-IV inhibitors (HR = 0.86; 95% CrI, 0.77-0.96).
In assessing CV mortality, SGLT2 inhibitors and GLP-1 receptor agonists were associated with lower CV mortality vs. DPP-IV inhibitors, with absolute risk differences of –0.8% and –0.5%, respectively.
The use of SGLT2 inhibitors was also associated with lower rates of HF events vs. control arms, with an absolute risk difference of –1.1% (HR = 0.62; 95% CrI, 0.54-0.72) and lower risk for MI vs. control arms, with an absolute risk difference of –0.6% (HR = 0.86; 95% CrI, 0.77-0.97).
Researchers also found that GLP-1 receptor agonists were associated with a higher risk for adverse events leading to trial withdrawal vs. SGLT2 inhibitors (absolute risk difference, 5.8%; HR = 1.8; 95% CrI, 1.44-2.25) and DPP-IV inhibitors (absolute risk difference, 3.1%; HR = 1.93; 95% CrI, 1.59-2.35).
“Although preferable, it is unlikely that drugs from these three classes will be tested against each other in well-powered randomized clinical trials,” Zheng said. “Real-world data with long follow-up will be important to provide evidence and support for the conclusions drawn from our study. In fact, results from the CVD-REAL study, a prospective observational study with propensity-matching, has shown similar findings to ours. Long-term data is essential to demonstrate whether these mortality benefits persist, and that these drugs are safe.” – by Regina Schaffer
For more information:
Sean L. Zheng, BM BCh , MA, MRCP, can be reached at Royal Brompton Hospital, Department of Cardiology, Sydney Street, London, U.K., SW3 6NP; email: sean.zheng@nhs.net.
Disclosures: One of the study authors reports he has received speaking fees and honoraria from Dexcom, Medtronic Diabetes, Novo Nordisk, Roche Diabetes, Sanofi and Takeda.