VIDEO: Meta-analysis: Mortality, safety data may favor SGLT2 inhibitors in T2DM

 

Sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide–1 (GLP-1) agonists were both associated with a lower mortality risk, compared with that seen with dipeptidyl peptidase–4 (DPP-4) inhibitors and in controls, in patients with type 2 diabetes, according to findings from a large network meta-analysis.

In addition, the GLP-1 agonists were associated with a higher risk of adverse events that led to study withdrawal, compared with SGLT2 inhibitors, according to the analysis conducted by Sean L. Zheng, BM BCh, of the department of endocrinology at the Imperial College Healthcare NHS Foundation Trust, London, and his coinvestigators.

“Of the 3 classes tested, SGLT2 inhibition may be preferred over the incretin-based therapies based on their association with lower mortality and their favorable adverse-event profile,” Dr. Zheng and his coinvestigators wrote in a report on the study published in JAMA.

Source: JAMA
For patients with type 2 diabetes who don’t achieve target glycemic control on metformin, Dr. Zheng and his coauthors noted, international guidelines recommend SGLT2 inhibitors or incretin-based treatments as a next step.

However, there has been little exploration of the relative clinical effectiveness of these drug classes, which has led to uncertainty about what treatment approach is optimal. “When no head-to-head trial exists, network meta-analysis can be used to estimate the effect,” the authors wrote.

To compare the efficacy of the drug classes in reducing mortality and cardiovascular outcomes, Dr. Zheng and his colleagues conducted a systematic review and meta-analysis of 236 randomized clinical trials including 176,310 participants.

The primary outcome of the study was all-cause mortality.

 

Both SGLT2 inhibitors and GLP-1 agonists were associated with significantly lower all-cause mortality than that seen in controls (placebo or no treatment), while DPP-4 inhibitors were not, investigators found in the meta-analysis.

For that endpoint, SGLT2 inhibitors had an absolute risk difference of –1.0%, with a hazard ratio of 0.80, and GLP-1 agonists had an absolute RD of –0.6% and an HR of 0.88. By contrast, DPP-4 inhibitors had an absolute RD of 0.1% and an HR of 1.02, according to the published report.

Moreover, when compared with DPP-4 inhibitors, SGLT2 inhibitors and GLP-1 agonists were associated with reduced all-cause mortality, with an absolute risk difference of –0.9% and –0.5%, respectively, they found.

SGLT2 inhibitors and GLP-1 agonists also were significantly associated with lower cardiovascular mortality than controls were, while SGLT2 inhibitors were significantly associated with lower heart failure event rates versus those seen controls, they also found.

 

Safety outcomes analysis showed that GLP-1 agonists, compared with SGLT2 inhibitors and DPP-4 inhibitors, had a higher risk of adverse events that led patients to withdraw from the study.

The DPP-4 inhibitors were associated with increased acute pancreatitis risk, according to the safety analysis. “SGLT2 inhibitors were associated with increased risk of genital infections but not urinary tract infections. There was a high degree of heterogeneity for lower-limb amputations driven by the significant increase in events with canagliflozin but neutral effects of empagliflozin,” they said.

“Careful treatment selection may be necessary to minimize these outcomes in at-risk patients,” Dr. Zheng and his coauthors concluded.

One author reported potential conflicts of interest with Roche Diabetes, Dexcom, Medtronics Diabetes, and others. Another was supported by a grant from the British Heart Foundation. No other conflicts were reported.

SOURCE: Zheng SL et al. JAMA. 2018;319(15):1580-91.

 

Sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide–1 (GLP-1) agonists were both associated with a lower mortality risk, compared with that seen with dipeptidyl peptidase–4 (DPP-4) inhibitors and in controls, in patients with type 2 diabetes, according to findings from a large network meta-analysis.

In addition, the GLP-1 agonists were associated with a higher risk of adverse events that led to study withdrawal, compared with SGLT2 inhibitors, according to the analysis conducted by Sean L. Zheng, BM BCh, of the department of endocrinology at the Imperial College Healthcare NHS Foundation Trust, London, and his coinvestigators.

“Of the 3 classes tested, SGLT2 inhibition may be preferred over the incretin-based therapies based on their association with lower mortality and their favorable adverse-event profile,” Dr. Zheng and his coinvestigators wrote in a report on the study published in JAMA.

Source: JAMA
For patients with type 2 diabetes who don’t achieve target glycemic control on metformin, Dr. Zheng and his coauthors noted, international guidelines recommend SGLT2 inhibitors or incretin-based treatments as a next step.

However, there has been little exploration of the relative clinical effectiveness of these drug classes, which has led to uncertainty about what treatment approach is optimal. “When no head-to-head trial exists, network meta-analysis can be used to estimate the effect,” the authors wrote.

To compare the efficacy of the drug classes in reducing mortality and cardiovascular outcomes, Dr. Zheng and his colleagues conducted a systematic review and meta-analysis of 236 randomized clinical trials including 176,310 participants.

The primary outcome of the study was all-cause mortality.

 

Both SGLT2 inhibitors and GLP-1 agonists were associated with significantly lower all-cause mortality than that seen in controls (placebo or no treatment), while DPP-4 inhibitors were not, investigators found in the meta-analysis.

For that endpoint, SGLT2 inhibitors had an absolute risk difference of –1.0%, with a hazard ratio of 0.80, and GLP-1 agonists had an absolute RD of –0.6% and an HR of 0.88. By contrast, DPP-4 inhibitors had an absolute RD of 0.1% and an HR of 1.02, according to the published report.

Moreover, when compared with DPP-4 inhibitors, SGLT2 inhibitors and GLP-1 agonists were associated with reduced all-cause mortality, with an absolute risk difference of –0.9% and –0.5%, respectively, they found.

SGLT2 inhibitors and GLP-1 agonists also were significantly associated with lower cardiovascular mortality than controls were, while SGLT2 inhibitors were significantly associated with lower heart failure event rates versus those seen controls, they also found.

 

Safety outcomes analysis showed that GLP-1 agonists, compared with SGLT2 inhibitors and DPP-4 inhibitors, had a higher risk of adverse events that led patients to withdraw from the study.

The DPP-4 inhibitors were associated with increased acute pancreatitis risk, according to the safety analysis. “SGLT2 inhibitors were associated with increased risk of genital infections but not urinary tract infections. There was a high degree of heterogeneity for lower-limb amputations driven by the significant increase in events with canagliflozin but neutral effects of empagliflozin,” they said.

“Careful treatment selection may be necessary to minimize these outcomes in at-risk patients,” Dr. Zheng and his coauthors concluded.

One author reported potential conflicts of interest with Roche Diabetes, Dexcom, Medtronics Diabetes, and others. Another was supported by a grant from the British Heart Foundation. No other conflicts were reported.

SOURCE: Zheng SL et al. JAMA. 2018;319(15):1580-91.

 

Sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide–1 (GLP-1) agonists were both associated with a lower mortality risk, compared with that seen with dipeptidyl peptidase–4 (DPP-4) inhibitors and in controls, in patients with type 2 diabetes, according to findings from a large network meta-analysis.

In addition, the GLP-1 agonists were associated with a higher risk of adverse events that led to study withdrawal, compared with SGLT2 inhibitors, according to the analysis conducted by Sean L. Zheng, BM BCh, of the department of endocrinology at the Imperial College Healthcare NHS Foundation Trust, London, and his coinvestigators.

“Of the 3 classes tested, SGLT2 inhibition may be preferred over the incretin-based therapies based on their association with lower mortality and their favorable adverse-event profile,” Dr. Zheng and his coinvestigators wrote in a report on the study published in JAMA.

Source: JAMA
For patients with type 2 diabetes who don’t achieve target glycemic control on metformin, Dr. Zheng and his coauthors noted, international guidelines recommend SGLT2 inhibitors or incretin-based treatments as a next step.

However, there has been little exploration of the relative clinical effectiveness of these drug classes, which has led to uncertainty about what treatment approach is optimal. “When no head-to-head trial exists, network meta-analysis can be used to estimate the effect,” the authors wrote.

To compare the efficacy of the drug classes in reducing mortality and cardiovascular outcomes, Dr. Zheng and his colleagues conducted a systematic review and meta-analysis of 236 randomized clinical trials including 176,310 participants.

The primary outcome of the study was all-cause mortality.

 

Both SGLT2 inhibitors and GLP-1 agonists were associated with significantly lower all-cause mortality than that seen in controls (placebo or no treatment), while DPP-4 inhibitors were not, investigators found in the meta-analysis.

For that endpoint, SGLT2 inhibitors had an absolute risk difference of –1.0%, with a hazard ratio of 0.80, and GLP-1 agonists had an absolute RD of –0.6% and an HR of 0.88. By contrast, DPP-4 inhibitors had an absolute RD of 0.1% and an HR of 1.02, according to the published report.

Moreover, when compared with DPP-4 inhibitors, SGLT2 inhibitors and GLP-1 agonists were associated with reduced all-cause mortality, with an absolute risk difference of –0.9% and –0.5%, respectively, they found.

SGLT2 inhibitors and GLP-1 agonists also were significantly associated with lower cardiovascular mortality than controls were, while SGLT2 inhibitors were significantly associated with lower heart failure event rates versus those seen controls, they also found.

 

Safety outcomes analysis showed that GLP-1 agonists, compared with SGLT2 inhibitors and DPP-4 inhibitors, had a higher risk of adverse events that led patients to withdraw from the study.

The DPP-4 inhibitors were associated with increased acute pancreatitis risk, according to the safety analysis. “SGLT2 inhibitors were associated with increased risk of genital infections but not urinary tract infections. There was a high degree of heterogeneity for lower-limb amputations driven by the significant increase in events with canagliflozin but neutral effects of empagliflozin,” they said.

“Careful treatment selection may be necessary to minimize these outcomes in at-risk patients,” Dr. Zheng and his coauthors concluded.

One author reported potential conflicts of interest with Roche Diabetes, Dexcom, Medtronics Diabetes, and others. Another was supported by a grant from the British Heart Foundation. No other conflicts were reported.

SOURCE: Zheng SL et al. JAMA. 2018;319(15):1580-91.