SGLT2 Inhibitor Impact on CV Risk: What We Know Now

May 5, 2015

While we wait for results from FDA-mandated CV outcomes studies by SGLT2I makers, there is plenty of (positive) speculation.

With each new class of agents approved to curb the progressive hyperglycemia of type 2 diabetes and its sequelae comes speculation-and hope-that other noxious disease pathways also will be affected.The potential for the sodium glucose cotransporter 2 inhibitors (SGLT2I) to significantly affect cardiovascular (CV) risk factors is still mostly an unknown, although evidence is accumulating for a beneficial association between specific SGLT2Is and blood pressure, weight, albuminuria, and visceral adiposity, among other factors.The slides above summarize what is currently known about clinical CV outcomes with SGLT2Is and highlights FDA-required CV outcomes trials in progress. References Inzucchi SE, Zinman B, Wanner C, et al. SGLT-2 Inhibitors and cardiovascular risk: Proposed pathways and review of ongoing trials.  Diab Vasc Dis Res. 2015 Mar;12(2):90-100. doi: 10.1177/1479164114559852. Epub 2015 Jan 14.Ferrannini E, Muscelli E, Frascerra S, et al. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest. 2014 Feb;124(2):499-508. doi: 10.1172/JCI72227. Epub 2014 Jan 27.Hardy E, Ptanszynska A, de Bruin TWA, et al. Changes in lipid profiles of patients with type 2 diabetes mellitus on dapagliflozin therapy.  Diabetologia 2013; Suppl 947, 61.Hach T, Gerich J, Salsali A, et al. Empagliflozin improves glyaecemic parameters and cardiovascular risk factors in patients with type 2 diabetes: pooled data from four pivotal phase III trials.  Diabetes 2013; 62 (Suppl 1): LB 19 [69-LB] (abstract no 94).Sinclair A1, Bode B, Harris S, et al. Efficacy and safety of canagliflozin compared with placebo in older patients with type 2 diabetes mellitus: a pooled analysis of clinical studies. BMC Endocr Disord. 2014 Apr 18;14:37. doi: 10.1186/1472-6823-14-37.Vasilakou D, Karagiannis T, Athanasiadou E, et al. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2013 Aug 20;159(4):262-74. doi: 10.7326/0003-4819-159-4-201308200-00007.FDA Briefing Document NDA 202293. Dapagliflozin tablets 5 and 10 mg, http://fda.gov/downloads/AdvisoryCommittess/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM262994.pdfFDA Briefing Material, http://fda.gov/downloads/AdvisoryCommittess/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM334550.pdfDziuba J1, Alperin P, Racketa J, et al. Modeling effects of SGLT-2 inhibitor dapagliflozin treatment versus standard diabetes therapy on cardiovascular and microvascular outcomes. Diabetes Obes Metab. 2014 Jul;16(7):628-35. doi: 10.1111/dom.12261. Epub 2014 Feb 19.