London, UK—The ultimate goal in type 2 diabetes treatment is lowering the risk of mortality. Now, pharmacists can find out which commonly prescribed drugs are best at meeting that threshold.

The report, published in JAMA, focuses on different classes of drugs routinely used to lower blood sugar levels in patients with type 2 diabetes: sodium-glucose cotransporter 2 (SGLT-2) inhibitors, glucagon-like peptide 1(GLP-1) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors.

A study team led by researchers from Imperial College, London conducted a meta-analysis through October 2017 of 236 randomized clinical trials involving 176,310 study participants with type 2 diabetes.

Results indicated that SGLT-2 inhibitors or GLP-1 agonists had a greater association with lowered risk of death than DPP-4 inhibitors or the control groups receiving either placebos or no treatment. The researchers point to previous studies indicating that the treatments are currently prescribed to at least one in three patients with type 2 diabetes.

“Type 2 diabetes has become a global epidemic, with more cases than ever before. The three drug classes assessed here are being increasingly prescribed, yet until now there have been no clinical trials studying how these drugs compare to each other, and which type of drug could be the best option for patients,” explained lead author Sean Zheng, MA, MRCP, from the National Heart and Lung Institute at Imperial.

Based on the meta-analysis, Zheng and colleagues report the following:
* SGLT-2 inhibitors (absolute risk difference [RD], -1.0%; hazard ratio [HR], 0.80 [95% credible interval [CrI], 0.71 to 0.89]) and GLP-1 agonists (absolute RD, -0.6%; HR, 0.88 [95% CrI, 0.81 to 0.94]) were associated with significantly lower all-cause mortality than the control groups.
* SGLT-2 inhibitors (absolute RD, -0.9%; HR, 0.78 [95% CrI, 0.68 to 0.90]) and GLP-1 agonists (absolute RD, -0.5%; HR, 0.86 [95% CrI, 0.77 to 0.96]) were associated with lower mortality than DPP-4 inhibitors.
* DPP-4 inhibitors were not significantly associated with lower all-cause mortality (absolute RD, 0.1%; HR, 1.02 [95% CrI, 0.94 to 1.11]) than the control groups.
* SGLT-2 inhibitors (absolute RD, ?0.8%; HR, 0.79 [95% CrI, 0.69 to 0.91]) and GLP-1 agonists (absolute RD, -0.5%; HR, 0.85 [95% CrI, 0.77 to 0.94]) were significantly associated with lower cardiovascular mortality than the control groups.
* SGLT-2 inhibitors were significantly associated with lower rates of heart failure events (absolute RD, -1.1%; HR, 0.62 [95% CrI, 0.54 to 0.72]) and MI (absolute RD, -0.6%; HR, 0.86 [95% CrI, 0.77 to 0.97]) than the control groups.
* GLP-1 agonists were associated with a higher risk of adverse events leading to trial withdrawal than were SGLT-2 inhibitors (absolute RD, 5.8%; HR, 1.80 [95% CrI, 1.44 to 2.25]) and DPP-4 inhibitors (absolute RD, 3.1%; HR, 1.93 [95% CrI, 1.59 to 2.35]).

Translating those findings, study authors said SGLT-2 inhibitor drugs were linked to a 1% decrease in absolute risk of death, while GLP-1 agonist medications were associated with a decrease in absolute risk of death by 0.6%.

In terms of specific cardiovascular events such as myocardial infarction or stroke, SGLT-2 inhibitor drugs were associated with a 21% reduction in risk of dying, and GLP-1 agonist medication was associated with a 15% decline, according to further analysis of the results, which also identified a link between SGLT-2 inhibitors and reductions in heart-failure risks.

No reductions in risk of death from cardiovascular events was found with DPP-4 inhibitors, however.

“Patients with type 2 diabetes are at higher risk of dying from heart attacks or strokes, so we wanted to investigate which of these three treatments are most efficient at preventing death and cardiovascular diseases,” Zheng said. “Our hope is that in the crowded market that is diabetes medications, patients and their doctors have the necessary information to allow them to make informed decisions about long-term treatment strategies.”