Meta-analysis assesses sodium-glucose cotransporter 2 (SGLT2) inhibitors

Sodium-glucose cotransporter 2 inhibitors appear to be an effective option to lower blood sugars in type 2 diabetes, but there is insufficient evidence on their safety and long-term effects, a recent meta-analysis found.


Sodium-glucose cotransporter 2 (SGLT2) inhibitors (a new class of drugs that reduces renal glucose reabsorption, leading to increased glucose excretion) appear to be an effective option to lower blood sugars in type 2 diabetes, but there is insufficient evidence on their safety and long-term effects, a recent meta-analysis found.

The analysis included 45 studies (of more than 11,000 patients) in which SLGT2 inhibitors were compared with placebo and 13 studies (with more than 5,000 patients) comparing them to other drug options. Results were published by Annals of Internal Medicine on Aug. 20.

SGLT2 inhibitors improved hemoglobin A1c compared to placebo (mean difference, −0.66%; 95% CI, −0.73% to −0.58%), but not significantly compared to active comparators (mean difference, −0.06%; 95% CI, −0.18% to 0.05%). Compared to the other active drugs, SGLT2 inhibitors reduced body weight (mean difference, −1.8 kg; 95% CI, −3.5 to −0.1 kg) and systolic blood pressure (mean difference, −4.45 mm Hg; 95% CI, −5.73 to −3.18 mm Hg), but increased urinary and genital tract infections (odds ratios, 1.42 and 5.06, respectively). Data on cardiovascular outcomes and death were inconclusive and there were more breast and bladder cancer cases than expected in patients taking dapagliflozin (although this could result from detection bias, the analysis said).

The available evidence had a number of limitations, including many studies' use of last-observation-carried-forward (LOCF) methods to impute missing data. (Another article in the same issue of Annals explained more about the limitations of such methods.) Other limitations included industry funding, a lack of head-to-head trials and a focus on short-term efficacy outcomes.

Based on the existing evidence, SGLT2 inhibitors may improve short-term outcomes for patients with type 2 diabetes, but conclusions about safety and long-term outcomes await additional data. Future research should compare the SGLT2 inhibitors to each other and to existing antihyperglycemics, the review authors recommended.