Sodium-glucose cotransporter-2 (SGLT2) inhibitors, such as canagliflozin and dapagliflozin, may be associated with favorable renal and cardiovascular (CV) outcomes, improved glycated hemoglobin (HbA1c), and weight loss in patients with type 2 diabetes, according to findings from a systematic review published in Diabetes, Obesity and Metabolism.
While several SGLT2 inhibitors are used in the management of diabetes, there exists some gaps in knowledge regarding this drug class in the context of type 2 diabetes. To close these gaps, a team of researchers examined 46 systematic reviews of 175 randomized controlled trials that assessed the efficacy and safety of various SGLT2 inhibitors in the treatment of type 2 diabetes.
The systematic reviews in this review were published between 2014 and 2021 and examined SGLT2 inhibitors canagliflozin, dapagliflozin, empagliflozin, luseogliflozin, ipragliflozin, tofogliflozin, ertugliflozin, sotagliflozin, and bexagliflozin. These therapies were compared with either placebo (as an adjuvant to metformin and insulin), dipeptidyl peptidase-4 inhibitors, or any antidiabetic drug.
Treatment across studies was administered for at least 12 weeks. The overall pooled cohort included 136,096 participants. In regard to CV outcomes, treatment with SGLT2 inhibitors across 4 studies featured “clear evidence of benefit” for myocardial infarction, with odds ratios [ORs] and hazard ratios [HRs] ranging between 0.85 and 0.91. The use of SGLT2 also showed “clear evidence of benefit” in regard to CV mortality (OR/HR range, 0.67-0.86), heart failure (OR/HR range, 0.64-0.69), and a composite renal outcome of worsening renal function, end-stage renal disease, or renal death (relative risk [RR]/HR range, 0.55-0.63).
In addition, there was a “clear evidence of benefit” with SGLT2 inhibitors compared with placebo for HbA1c (mean difference [MD], -0.49% to -0.77% [5.4 to 8.4 mmol/mol]) and for weight (MD, -1.09 kg to -2.99 kg).
There was a “possible benefit” for SGLT2 inhibitors in regard to major adverse CV events across 4 systematic reviews (OR/HR range, 0.80-0.89). In contrast, SGLT2 inhibitors featured “clear evidence of no effect or equivalence” for stroke and fractures. Also, there was a “clear evidence of harm” with SGLT2 inhibitors for genital infections (RR/OR range, 2.06-5.25) and ketoacidosis (HR/OR range, 1.36-2.20).
Given that this was an overview of systematic reviews and was designed to be a narrative synthesis, the researchers suggest the findings are limited without an additional meta-analysis of all the pooled data from the randomized controlled trials. However, the researchers concluded the study “showed the efficacy of SGLT2 inhibitors in relation to cardiovascular and renal outcomes, and this has a relevant impact on clinical practice.”
Augusto GA, Cassola N, Dualib PM, Saconato H, Melnik T. Sodium-glucose cotransporter-2 inhibitors for type 2 diabetes mellitus in adults: An overview of 46 systematic reviews. Diabetes Obes Metab. Published online June 17, 2021. doi:10.1111/dom.14470